Tablet Press Compression Tooling Assembly for the Formation of Soft-Chew Tablets and

Related Methods

RELATED APPLICATIONS

[0001] The present application claims the benefit of U.S. Provisional Patent Application Serial No. 63/333,159, filed April 21, 2022, entitled Tablet Press Compression Tooling Assembly, which is hereby incorporated in its entirety by reference herein.

BACKGROUND

[0002] 1. Field

[0003] The present invention relates to products and processes for the manufacture of soft- chewable tablet pharmaceutical, or nutritional, dosage forms for the oral administration of active pharmaceutical ingredients or nutritional agents.

[0004] 2. Discussion of Prior Art

[0005] Chewable pharmaceutical dosage units, such as chewable tablets and soft-chewable tablets, are known and have been commercialized for use with pediatric, geriatric, and involuntary patient populations. Such dosage forms have also been used for subjects that, by instinct, will not accept medication meant to be swallowed. Chewable tablets are also useful with competent patients as an alternative to tablets or capsules that must be swallowed whole. The formulation of a drug into a chewable dosage form can increase patient acceptance of a medication in patients that resist or are unable to swallow conventional tablets or capsules.

[0006] Oral dosage forms, such as chewable compressed tablets, formulated using conventional ingredients tend to be gritty or otherwise unappealing to many patients. Traditionally, tablets compressed on a compression machine are formulated to produce tablets having a hardness of more than ten kiloponds (10 kp). Tablets having lower hardness levels (i.e., less than 10 kp) are often discouraged by the prior art to enable formation of tablets having friability values within acceptable ranges.

[0007] A process for manufacturing soft-chewable dosage form for drug delivery is described in U.S. Patent No. 6,387,381. It discloses a soft-chewable medication vehicle for drug delivery of an active ingredient to animal or human subjects, not containing ingredients of animal origin, without the use of heat and without the addition of water. The formed mixture was formed into individual chunks using a Formax F6™ molding machine with dies for production of chunk-like shapes, and packaged for storage. Machines for the production of molded food patties have been described as being useful for the manufacturing of soft-chews for administration to non-human animals. Such machines arc molding machines that have been originally developed for use in producing molded food products, for example the Formax F6™ molding machine made by the Formax Corporation. [0008] The use of extruders, forming machines, and rotary molding machines to manufacture pharmaceutical tablets can be problematic. For instance, it is difficult to control the weight and physical form of tablets formed by such devices. Typically, excessive conditioning of the initial tablet structure (e.g., drying or curing) after formation using such devices is required to achieve the desired shape and structure of the finished tablet. Moreover, the use of such technologies, equipment, and processes is complex, cumbersome, and not traditionally employed by typical pharmaceutical manufacturing facilities producing solid oral dosage forms.

[0009] Thus, there is a need for soft-chew tablet formulations, and processes of making the same, that enable large scale manufacture using equipment traditionally employed in the pharmaceutical manufacturing industry; including, but not limited to, rotary (tablet) compression presses.

[0010] A wide range of tablet presses are used in the pharmaceutical industry to compress one or more ingredients into a solid dosage form (i.e., a tablet). More particularly, a mixture of pharmaceutical ingredients (tablet formulation), often in the form of granules, is introduced to a tablet press. The tablet formulation is fed, often by a hopper, to a die cavity where metered amounts of the formulation are compressed within a die bore. Generally, an upper punch and a lower punch are arranged above and below the die bore. Once the desired amount of tablet formulation is in the die, the upper and lower punches are moved toward each other to compress the tablet formulation within the die bore to the shape of a tablet.

[0011] A common problem during the tablet compression process is sticking. Sticking occurs when some of the tablet formulation being compressed attaches and sticks to the compression tooling (e.g., the punch tip/face and/or the wall of the die bore). Sticking results in defective tablets having cavities and/or other unwanted irregularities on the outer surfaces. Picking is a specific type of sticking that refers to granules or particles of the tablet formulation sticking on the compression tooling due to embossing (e.g., break lines, letters, numbers, logos, etc.) on the face of the punch tips, such as the letter or numerals of the tablet logo or identifier.

[0012] Known means of preventing sticking include decreasing the moisture content of the tablet formulation (decreasing the moisture content of the granules), adding lubricating agents and/or anti-sticking agents to the tablet formulation, controlling the humidity and/or temperature of the working environment, polishing the compression tooling, and/or using compression tooling with a specialized coating. However, known anti- sticking means arc not effective for all tablet formulations. For example, some soft-chew tablet formulations (e.g., soft-chew granules) have a moisture content ranging from 5% to 15% or more and tend to be hygroscopic. Many known antisticking means do not effectively prevent sticking with such soft-chew formulations, and others cannot be used without compromising the desired characteristics of the soft-chew tablet to be formed (i.e., hardness, friability, etc.).

[0013] Thus, there is a need for an effective anti-sticking means that is suitable for uses with tablet formulations that are sticky and/or that require moisture content within certain ranges.

[0014] This background discussion is intended to provide information related to the present invention which is not necessarily prior art.

SUMMARY OF THE INVENTION

[0015] The present invention overcomes the disadvantages and shortcomings of known chewable dosage forms, and known processes for making the same, by providing a simplified process for manufacturing soft-chewable dosage units using conventional pharmaceutical equipment and compression techniques (e.g., a rotary tablet press).

[0016] Dosage forms of the present invention include palatable, soft-chewable pharmaceutical compositions for oral administration to an involuntary subject population (e.g., very young children, senile patients, animals, etc.) that includes a therapeutically effective amount of a pharmaceutically active ingredient, in an immediate or controlled release form, and a palatability improving agent in an amount sufficient to make the pharmaceutical composition palatable to the subject population. As used herein, the phrase “involuntary subject population” is defined as patients who cannot be conventionally instructed to chew and/or swallow conventional hard chew tablets or capsules.

[0017] The texture of a chewable dosage form is an important factor in the acceptance of oral dosage forms by patients in need of medication. Soft-chewable tablets, having a soft texture, pleasant mouthfeel, and palatable taste with adequate flavoring agents, provide a solution to such problems. In addition, these features can address the problem of the disagreeable taste of many active pharmaceutical ingredients. The soft-chew dosage forms of the present invention are formulated to address texture problems attributed to the dry, dusty, granular, and pulverant nature of many pharmaceutical ingredients. [0018] The soft-chewable pharmaceutical dosage units (soft-chew tablets) of the present invention arc solid at room temperature and have lower hardness and higher moisture content relative to conventional tablets or hard-chew tablets. The soft-chew tablets of the present invention have a soft texture, low hardness, are designed to be chewed and swallowed, and will not appreciably dissolve in the mouth of the patient. The soft-chew tablets of the present invention exhibit a plastic rheological behavior and can be formed into many different shapes using a wide range of manufacturing processes. After formation, the soft-chew tablets of the present invention are dimensionally stable.

[0019] In certain embodiments, the soft-chew tablets of the present invention are prepared using conventional methods, such as wet or dry granulation processes. Preferably, the soft-chew tablets of the present invention are formulated using pharmaceutical grade ingredients.

[0020] It has been found that soft-chew tablets of the prior art can be manufactured more efficiently, reliably, and consistently, using a tablet press. The compressed soft-chew dosage forms of the present invention have hardness values of less than 2 kp, or may have hardness values of less than 1 kp, or may have no measurable hardness when measured with a tablet hardness tester. Despite their low hardness, the soft-chew tablets of the present invention exhibit friability values of less than 1.0%, or less than 0.5%, or less than 0.1% when determined in accordance with the USP friability test at 100-rotations, 200-rotations, or 300-rotations.

[0021] Certain aspects of the present invention relate to a tablet compression tooling that provides an anti-sticking means for tablet formulations that are sticky and/or necessarily moist. In certain embodiments of the present invention, the tablet compression tool assembly includes an upper punch, a lower punch, and a die.

[0022] This summary is provided to introduce a selection of concepts in a simplified form that are further described below in the detailed description. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter. Other aspects and advantages of the present invention will be apparent from the following detailed description of the embodiments and the accompanying drawing figures.

BRIEF DESCRIPTION OF THE DRAWING FIGURES

[0023] Certain aspects of certain embodiments of the invention are described in detail below with reference to the attached figures, wherein: [0024] FTG. 1 is a side perspective view of a tablet compression tool assembly configured in accordance with one embodiment of the present invention;

[0025] FIG. 2 is an exploded perspective of the tablet compression tool assembly of FIG. 1;

[0026] FIG. 3 is an enlarged, partially sectioned cross-sectional view of the tablet compression tool assembly of FIG. 1;

[0027] FIG. 4 is an exploded perspective of the upper punch portion of the tablet compression tool assembly of FIG. 1;

[0028] FIG. 5 is an exploded perspective of the lower punch portion of the tablet compression tool assembly of FIG. 1;

[0029] FIG. 6 is a perspective of the die portion of the tablet compression tool assembly of FIG. 1; and

[0030] FIG. 7 is a side perspective view of a tablet compression tool assembly configured in accordance with one embodiment of the present invention.

[0031] The figures do not limit the present invention to the specific embodiments disclosed and described herein. The emphasis instead being placed upon clearly illustrating certain principles of a preferred embodiment.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0032] In addition to the other terms expressly defined herein, for the purposes of this disclosure and claims, the following terms, units, words, and phrases shall have the respective meanings assigned to them as follows (and cognate expressions shall bear corresponding meanings): the unit symbol “%w/w” means percent-by-weight, the amount/concentration of one or more components in a group of components, which can be calculated by dividing the numerical value for the mass of one or more components in a group of components by the numerical value for the mass of all of the components in the group and multiplying the quotient by 100; the unit symbol “°C” means degree(s) in Celsius, a unit of temperature on the Celsius scale; the phrase “active agent” means an active ingredient; the phrase “active ingredient” means an active pharmaceutical ingredient or a nutritional agent (an active ingredient may be in granular form and coated, or further coated, with a suitable coating. For example, the coating could be a coating polymer that coats and protects the active ingredient, or masks an offensive taste and/or offensive odor. In certain embodiments, the coating could be a functional coating (e.g., an extended-release coating, delayed-release coating, controlled-release coating, barrier coating, or a combination thereof)); the phrase “active pharmaceutical ingredient” means a substance used in a pharmaceutical dosage form, intended to furnish pharmacological activity or to otherwise have direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease, and substances that have, or are thought to have, a direct effect in restoring, correcting, or modifying physiological functions in a patient population (an active pharmaceutical ingredient may include any approved or experimental drug. By “approved,” it is meant that the drug is approved for human or veterinary use by a regulatory agency in any country that makes such drug approvals. For example, the pharmaceutically active ingredient may be selected from an anesthetic agent, anthelmintic agent, analgesic agent, steroid, corticosteroid agent, non-steroidal anti-inflammatory drug (NSAID) agent, antiemetic agent, anti- thyroidal agent, parasiticidal agent, appetite stimulant, antihistamine agent, antifungal agent, antiprotozoal agent, or anti-depressant); the acronym “API” means active pharmaceutical ingredient; the acronym “ASTM” means American Standard Test Sieve Series; the acronym “BHA” means the compound butylated hydroxyanisole; the acronym “BHT” means the compound butylated hydroxytoluene; the phrase “dextromethorphan HBr” means dextromethorphan hydrobromide; the phrase “diphenhydramine HC1” means diphenhydramine hydrochloride; the term “EDTA” means the compound sodium ethylenediaminetetraacetic acid; the acronym “FDA” means the U.S. Food and Drug Administration; the term “fluid” means a material that is flowable or malleable fluid material may be a viscous liquid, with a viscosity comparable, for example, to water, vegetable oil, honey, or peanut butter.; the unit symbol “g” means gram(s), a unit of mass equal to 0.001 kg; the acronym “HDPE” means high density polyethylene; the unit symbol “kfg” means kilogram-force, a gravitational metric unit of force equal to 9.80665 N; the unit symbol “kg” means kilogram(s), the SI unit of mass; the unit symbol “kN” means kilonewton, which is equal to 1000 N; the unit symbol “kp” means kilopond(s), a unit of measurement for tablet hardness, which is sometimes referred to as a kilogram-force (kfg) and is equal to 9.80665 N; the unit symbol “lb” means pound, a unit of measurement for tablet hardness; the acronym “MCT” means medium chain triglycerides; the unit symbol “mg” means milligram(s), a unit of mass equal to 0.000001 kg; the unit symbol “mb” means milliliter, a unit of volume equal to 0.000001 cubic meters; the unit symbol “mm” means millimeter; the unit symbol “N” means Newton, the International System of Units (SI) unit of measurement for force; the acronym “ND” means not detected; the acronym “NSAID” means a non-steroidal anti-inflammatory drug; the phrase “nutritional agent” means minerals, vitamins, nutraceutical agents, and other supplements, including derivatives, salts (and the like), and/or mixtures of the foregoing; the acronym “PET” means polyethylene terephthalate; the phrase “phenylephrine HQ” means phenylephrine hydrochloride; the acronym “POM” means the compound polyoxymethylene; the acronym “PTFE” means the compound polytetrafluoroethylene; the acronym “q.s.” means quantity sufficient; the acronym “RPM” means rotations per minute; the unit symbol “SC” means Strong- Cobb, a unit of measurement for tablet hardness, which is equal to approximately 0.7 kilogram of force or about 7 N; the acronym “SD” means storage duration; the phrase “soft-chew tablet” means a solid, soft chewable, semi-plastic oral dosage form for the delivery of an active ingredient; the phrase “USP disintegration test” means the harmonized standard for determination of whether a tablet will disintegrate within the prescribed time when placed in a liquid medium as provided in general chapter <701> of the United States Pharmacopeia, which is hereby incorporated in its entirety by reference herein; the phrase “USP friability test” means the harmonized standard for determination of compressed tablet friability provided in general chapter <1216> of the United States Pharmacopeia, which is hereby incorporated in its entirety by reference herein (it is particularly noted that the USP friability test calls for 100-drum-rotations however, if a friability value is provided herein for a greater number of drum rotations, it should be understood that all other guidelines for determining friability under general chapter <1216> were followed to obtain such friability value); the phrase “wet granules” means granules having a water content in the range of 2 %w/w to 15 %w/w; and the unit symbol “p” means micron, which is equal to 0.001 mm.

[0033] The inventors have discovered that by stepwise formulation according to the present invention, conventional tablet compression techniques (such as a tablet press), with slight modification, can be used to form very soft tablets with a uniform composition.

[0034] In certain embodiments of the present invention, dosage forms are formed by making a soft chew mass. The soft chew mass includes various excipients including softening agent(s), humectant(s), dry ingredients, granulation ingredients (granulation aid ingredients and intragranulation ingredients), extra-granulation ingredients, and active ingredients. During the granulation process, granules of the soft chew mass are formed, passed through appropriate screens for sizing, and lubricated with extra granular excipients then compressed using a tablet press.

[0035] Soft-chew tablets of the present invention have a soft texture, low hardness, and may be chewed and swallowed. The texture of the soft-chew tablet is such that it does not appreciably dissolve in the mouth. Soft-chew tablets of the present invention may be designed to be chewed and swallowed by a human or an animal.

[0036] In certain embodiments of the present invention, soft-chew tablets are manufactured by a process of: (a) mixing at least one active ingredient with at least one dry or liquid component to form a liquid; (b) blending dry ingredients having at least one of each of a bulking agent, a lipid, a flavoring agent, a disintegrating agent, a texturing agent, a binding agent, a preservative, a lubricating agent, an anti- sticking agent, and, optionally, a surfactant to form a uniform dry ingredient mixture; (c) blending the premix and the uniform dry ingredient mixture to form a granulated compacted soft-chew mass; (d) sifting the granulated compacted soft-chew mass through at least one sifting screen to form uniform granules of the soft-chew mass; and (e) adding a lubricant or anti sticking agent to the uniform granules of the soft-chew mass and compressing the resulting mixture in a tablet press to form soft-chew tablets.

[0037] In certain embodiments of the present invention, two or more mixtures are prepared in the inventive process. One mixture is a fluid premix containing the active ingredient, and the other mixture is a blend of dry ingredients. The fluid premix and dry ingredient blend are mixed together to form a soft-chew mass.

[0038] Texturing agents are additives present in formulations in order to primarily enhance the consistency and the soft feel of the finished product. In certain embodiments of the present invention, texturing agents are used to improve the overall texture or mouthfeel of the soft-chew tablets. In certain embodiments, texturing agents are present in the formulation in concentrations ranging from about 5 %w/w to about 50 %w/w. In certain embodiments, the composition of the soft-chew tablets of the present invention include a texturing agent, selected from the group including, comprising modified corn starches, poly(ethylene) oxide, microcrystalline cellulose, modified microcrystalline cellulose, com syrup solids, dried glucose syrup, maltodextrin, partially hydrogenated guar gum (PHGG), milk powder, solanum starch, and the like.

[0039] In certain embodiments, the composition of the soft-chew tablets of the present invention include one or more fillers. A filler may be used to increase the total mass of the chewable formulation to a manageable size or to enhance the flow properties of the final powder or granules to be compressed.

[0040] In certain embodiments, the composition of the soft-chew tablets of the present invention include a binding agent. The binding agent may be polyethylene glycol. The polyethylene glycol may be admixed to dry ingredients for mixing. The polyethylene glycol may be melted and added to at least one other dry ingredient and mixed to form the uniform dry ingredient mixture.

[0041] In certain embodiments, the composition of the soft-chew tablets of the present invention include microcrystalline cellulose as a bulking agent.

[0042] In certain embodiments, the composition of the soft-chew tablets of the present invention include a lipid and microcrystalline cellulose in a ratio of about 2:1 to about 1:2.5, weight-by- weight, and wherein the tablet is manufactured by compression on a tablet press.

[0043] In certain embodiments of the present invention, one or more diluents may be used in combination with silicified microcrystalline cellulose. Examples of diluents include starches and their derivatives (e.g., hydrogenated starch hydrolysate), celluloses and their derivatives (e.g., cellulose acetate), protein matrices (e.g., soy protein, dextrates, wheat gluten, whey, corn cob, com gluten), carbohydrates (e.g., maltodextrin, polydextrose), sugars and sugar alcohols (e.g., glucose, lactose, fructose, maltose, dextrose, sucrose, maltitol, xylitol, isomalt, mannitol), silicates, dextrates, kaolin, poly methacrylates, talc, salts (e.g., calcium phosphates, calcium sulfate, magnesium carbonate) or any combination of any two or more thereof.

[0044] In certain embodiments, the composition of the soft-chew tablets of the present invention includes a starch, or a modified starch, or a mixture of starch and modified starch.

[0045] In certain embodiments, the composition of the soft-chew tablets of the present invention includes one or more binders. Binders improve the binding properties of the compacted mass, to assist the formation of compact dosage units. Any suitable binder known in the art may be used. For example, binders that may be used according to the present invention may include, but are not limited to, gums (e.g., xanthan gum and guar gum), alginates, celluloses and their derivatives (e.g., methylcellulose and microcrystalline cellulose), lipids (e.g., fats and oils), starches and their derivatives, dextrins, povidones, silicates, polymethacrylates, polyethylene oxides, waxes, chitosan, polycarbophil, agar, carbomers, and combinations of the foregoing.

[0046] In certain embodiments, the composition of the soft-chew tablets of the present invention includes one or more palatability enhancers. Palatability enhancers improve the taste of a material. Advantageously, palatability enhancers may improve the palatability of soft-chew tablet formulations comprising bitter, acrid, obnoxious, unpleasant, or otherwise unpalatable active agents. [0047] Tn certain embodiments of the present invention, the palatability enhancer is a taste masking agent, a flavoring agent, an aroma modifier, or a taste modifier, or any combination of any two or more thereof.

[0048] Flavoring agents may be used to improve the palatability of the soft-chew tablets of the present invention. Any type of flavoring agent can be used provided it improves the palatability of the product, typically by improving its taste and/or smell. The use of a flavoring agent may also assist with dose compliance. Flavors can be natural (derived from animal or plant sources), semisynthetic, or artificial. In one embodiment, the flavoring agent is an artificial flavoring agent, semi- synthetic flavoring agent, a natural flavoring agent, or nature identical flavoring agent. In certain preferred embodiments of the present invention, flavoring agents are present in a concentration ranging from about 2 to about 30 %w/w. Suitable flavoring agents include, but are not limited to, spray dried banana powder, mixed fruit powder, pineapple powder, strawberry powder, watermelon powder, honey powder, cocoa powder, grape powder, raspberry powder, mixed berry powder, orange powder, mango powder, mushroom powder, etc. In certain embodiments of the present invention, a taste modifier is used to improve the taste of the soft- chew tablets. In certain embodiments, the composition of the soft-chew tablets of the present invention includes a taste modifier selected from the group comprising citric acid, malic acid, lactic acid, hydroxypropyl-B -cyclodextrin, bitter masker, bitter blocker, calcium carboxy methyl cellulose, etc.

[0049] In certain embodiments, the composition of the soft-chew tablets of the present invention includes liquid components that are absorbed on the surface of a lipid absorbing pharmaceutical ingredient selected from one or more of microcrystalline cellulose, silicified microcrystalline cellulose, and a combination of microcrystalline cellulose and guar gum. The liquid components absorbed on the surface of the lipid absorbing pharmaceutical ingredient may be mixed with the dry ingredient mixture and then sifted again through at least one sifting screen to form further granules of the soft-chew composition mixture. In an embodiment, a nutritional agent or a pharmaceutically active ingredient is admixed with the liquid components prior to mixing with the lipid absorbing pharmaceutical ingredient.

[0050] In certain embodiments of the present invention, plasticizers may be added to the formulation to improve plasticity and malleability of the soft-chew tablets of the present invention. In certain embodiments, a plasticizer may be selected from alcohols, glycols (such as propylene glycol), lanolin, wool fat, liquid paraffin, mineral oil, petrolatum, benzyl phenylformate, chlorobutanol, diethyl phthalate, glycerol, polyethylene glycol, sorbitol, triacctin, benzyl phenyl formate, dibutyl sebacate, tributyl citrate, triethyl citrate, or any combination of any two or more thereof. Other plasticizers known in the art may also be used.

[0051] In certain embodiments, the composition of the soft-chew tablets of the present invention includes a non-active ingredient including one or more of a starch, a polysaccharide, a humectant, a polyol, water-soluble poly(ethylene oxide) resin.

[0052] In certain embodiments, the composition of the soft-chew tablets of the present invention includes a humectant. A humectant is used to retain moisture in the dosage unit. Humectants may be selected from sugars, hydrogenated starch hydrolysate, etc. Suitable liquid humectants include, but are not limited to, glycols, polyols, sugar alcohols, com syrup or any combination of any two or more thereof. Other humectants known in the art may also be used.

[0053] In certain embodiments, the composition of the soft-chew tablets of the present invention includes an antioxidant. An antioxidant inhibits oxidation and may be of benefit as a preservative, or to maintain the chemical stability of an active or inactive ingredient. An antioxidant may be selected from propyl gallate, ascorbic acid and its derivatives, sodium formaldehyde sulfoxylate, malic acid, fumaric acid, editic acid, thiols, polyphenols, EDTA, sodium ascorbate, sodium metabisulfite, butylated hydroxytoluene, butylated hydroxyanisole, butylated hydroxyanisole and butylated hydroxytoluene co-processed with zea mays oil or natural substances such as flavonoids, tocopherols, carotenes, cysteine, or any combination of any two or more thereof. Other antioxidants known in the art may also be used. The antioxidants are generally added to the formulation in amounts ranging from about 0.01 %w/w to about 2 %w/w, with amounts ranging from about 0.01 %w/w to about 1.0 % / being especially preferred.

[0054] In certain embodiments, the composition of the soft-chew tablets of the present invention includes a preservative selected from the group including parabens (e.g., methylparaben and/or propylparaben), benzalkonium chloride, benzethonium chloride, benzoic acid, citric acid, fumaric acid, bronopol, butylparaben, cetrimide, chlorobutanol, chlorocresol, cresol, ethylparaben, imidurea, phenol, phenoxyethanol, phenylethyl alcohol, potassium sorbate, sodium benzoate, sodium propionate, and sorbic acid. Other preservatives known in the art may also be used.

[0055] In certain embodiments, the composition of the soft-chew tablets of the present invention includes a nonaqueous solvent, for example glycerin or propylene glycol. A non-aqueous solvent may disperse, solubilize, or enhance solubilization of an active ingredient. The non-aqueous solvent may also enhance the binding of the formulation and/or the consistency and texture of the soft-chewable dosage form.

[0056] In certain embodiments, the composition of the soft-chew tablets of the present invention includes a disintegrating agent. A disintegrating agent may be used to enable the inventive chewable tablets to break down on contact with water, saliva, or gastric fluid in the stomach to quickly release the active ingredient. A disintegrating agent may be selected from cross-linked povidones, croscarmellose sodium, sodium starch glycollate, celluloses and their derivatives, starches and their derivatives, gelatin, silicon dioxide, or any combination of any two or more thereof. Other disintegrating agents known in the art may also be used. Disintegration may be tested and measured in accordance with the USP disintegration test, using water as the medium.

[0057] In certain embodiments of the present invention, a granulated compacted soft-chew mass is formed, and the mass is dried by equipment using direct or indirect conduction heat applied to a static solid bed, a moving solid bed, or a fluidized solid bed. The granulated mass may be dried at room temperature, for example about 25 °C plus-or-minus 10 °C or may be dried at a controlled temperature of about 50 °C or less. In certain embodiments, no heating for drying is employed to form the soft-chew tablets.

[0058] In certain embodiments of the present invention, the process of manufacturing soft-chew tablets may include sifting, or milling, of dry components or a granulated mass, or a mixture of both through sifting screens with mesh sizes commonly known in the art. Mesh sizes for sifting screens may include Mesh # 4 or 5 or 6 or 7 or 8 or 10 or 12 or 14 or 16 or 18 or 20 or 25 or 30 or 35 or 40 or 45 or 50 or 60 or other mesh sizes commonly known in the art. Components may be sifted through at two or more screens with different mesh sizes one after other in gradual or random order of mesh sizes.

[0059] In certain embodiments of the present invention, the dry ingredient mixture or the granulated compacted soft-chew mass is sifted through sifting equipment using impaction, attrition, compression, or cutting.

[0060] In certain embodiments of the present invention, the dry ingredient mixture or the granulated compacted soft-chew mass is uniformly mixed using equipment providing diffusion mixing, convection mixing, or pneumatic mixing. [0061 ] Tn certain embodiments of the present invention, a pre-compression force may be applied to the granulated compacted soft-chew mass before application of the primary compression force that forms the soft-chew tablet.

[0062] In certain embodiments of the present invention, the granulated compacted soft-chew mass may be fed into a compression die by gravity feed, power assisted feed, by centrifugal force, or by compression coating.

[0063] In certain embodiments of the present invention, the soft-chew tablets may incorporate an abuse-deterrent technology, which can include one or more high-melting-point excipients that resist heating and injecting; taste modifiers that resist covert administration, snorting (i.e., ingestion of a powdered material through the nose) and dose dumping (i.e., extraction of active pharmaceutical ingredients (API) from tablets); water insoluble excipients that resist extraction and drink adulteration; waxy excipients that resist snorting; viscosity modifiers that resist dissolution, injection and dose dumping; low-density excipients that resist drink adulteration; and dyes, that resist adulteration.

[0064] In certain embodiments of the present invention, a soft-chew tablet is manufactured by a process of: (a) mixing an intragranular mixture with a softening agent and a granulation dispersion to form a wet mass; (b) mixing and sifting the wet mass with an extragranular mixture to form granules; (c) lubricating the first granules to form lubricated granules; and (d) compressing the lubricated granules in a tablet press to from soft-chew tablets.

[0065] In certain embodiments of the present invention, the intragranular mixture is a mixture of two or more intragranular ingredients including dried glucose syrup, mannitol, sorbitol powder, partially pregelatinized starch, partially hydrogenated guar gum (PHGG), carboxy methylcellulose calcium, solanum starch, monoammonium glycyrrhizinate, milk powder, croscarmellose sodium, calcium gluconate monohydrate, carnauba wax, flavor agent, maltodextrin, sodium starch glycolate, citric acid anhydrous, magnesium stearate, sodium bicarbonate, sucralose, xylitol, crospovidone, hydroxypropyl beta-cyclodextrin, potassium sorbate, sodium benzoate, sodium caseinate, Advantol 300 (co-processed excipients), albumin, granulated corn starch, dextrose anhydrous, magnesium hydroxide, silicified microcrystalline cellulose, soy protein, whey protein, and xanthan gum. In certain preferred embodiments, the intragranular mixture is formed by cosifting the intragranular ingredients at least two times using a sieve as described in greater detail in the Examples hereinbelow. [0066] Tn certain embodiments of the present invention, softening agents are used in combination with one or more humectants to enhance the softness of the soft-chew tablet. In certain embodiments of the present invention, at least one softening agent is selected from the group comprising canola oil, cocoa butter, coconut oil, corn oil, flaxseed oil, glycols (such as propylene glycol), hydrogenated vegetable oils, lanolin, lecithin, lipids, liquid paraffin, MCT oil, mineral oil, natural substances such as flavonoids, olive oil, palm oil, polyethylene glycol, rosemary oil, seed oil, simethicone, soybean oil, thyme oil, triglycerides or medium chain triglycerides (MCT), vegetable oils, wool fat, zea mays oil, and other suitable lipids.

[0067] In certain embodiments of the present invention, the granulation dispersion is a combination of two or more ingredients including glycerin, maltitol solution, sucralose, stevia (natural sweetener), citric acid anhydrous, bitter masker, polyvinylpyrrolidone, polyethylene glycol, hydroxypropyl beta-cyclodextrin, non crystallizing sorbitol solution, soya lecithin, flavor agents, and color agents. In certain preferred embodiments, the granulation dispersion is formed by mixing two or more ingredients until a uniform granulation dispersion is formed as described in greater detail in the Examples hereinbelow.

[0068] In certain embodiments of the present invention, the wet mass is a mixture of the intragranular mixture, the lipid, and the granulation dispersion. In certain preferred embodiments, the intragranular mixture, the lipid, and the granulation dispersion are mixed using a rapid mixer granulator to form a wet mass as described in greater detail in the Examples hereinbelow.

[0069] In certain embodiments of the present invention, the extragranular mixture is a mixture of two or more extragranular ingredients including mannitol, partially pregelatinized starch, partially hydrogenated guar gum (PHGG), carboxymethylcellulose calcium, solanum starch, flavor agent, crospovidone, milk powder, citric acid anhydrous, xylitol, croscarmellose sodium, silicified microcrystalline cellulose, sorbitol (powder), Advantol 300 (co-processed ingredients), and granulated corn starch. In certain preferred embodiments, the extragranular mixture is formed by co-sifting the extragranular ingredients at least two times using a sieve as described in greater detail in the Examples hereinbelow.

[0070] In certain embodiments of the present invention, the wet mass is mixed with the extragranular mixture to form granules. In certain preferred embodiments, the wet mass and the extragranular mixture are mixed using a cone mill to form milled granules, as described in greater detail in the Examples hereinbelow. [0071 ] Tn certain embodiments of the present invention, the milled granules are lubricated with a lubricating agent to form lubricated granules. In certain embodiments of the present invention, a lubricating agent is selected from at least one of carnauba wax and/or magnesium stearate. In certain preferred embodiments, the lubricated granules are formed by lubricating the milled granules as described in greater detail in the Examples hereinbelow.

[0072] In certain embodiments of the present invention, the lubricated granules are compressed to form one or more soft-chew tablets. In certain preferred embodiments of the present invention, the lubricated granules are compressed using a tablet press to form one or more soft-chew tablets. A tablet press is a mechanical device that compresses powder into tablets of uniform size and weight. A press can be used to manufacture tablets/pellets of a wide variety of materials, including pharmaceuticals, cleaning products, and cosmetics. There are two types of press machines, eccentric-type and rotary-type. The rotary-type is generally more widely used, because it facilitates high production performance with narrow weight variation along with ease of use.

[0073] In certain preferred embodiments, as provided in the Examples included hereinbelow, one or more active ingredients are included in the intragranular mixture. In certain preferred embodiments, as provided in the Examples included hereinbelow, the softening agent includes an active ingredient, such as simethicone. In certain preferred embodiments, as provided in the Examples included hereinbelow, an active ingredient is included in the granulation dispersion. In certain preferred embodiments, as provided in the Examples included hereinbelow, an active ingredient is included in the extragranular mixture.

[0074] In certain embodiments of the present invention, the active ingredient may be dissolved, emulsified, or suspended in a non-aqueous solvent before addition. The active ingredient may be soluble, partially soluble, or insoluble in water. In certain embodiments of the present invention, the active ingredient is added to the soft-chew tablet composition by dry blending. In certain embodiments of the present invention, the active ingredient may be conjugated with other ingredients, such as cyclodextrins, surfactants, solubility or bioavailability enhancers, etc., to inhibit interactions with other excipients or with the environment, or to promote the chemical stability, improve solubility, enhance bioavailability, or improve the palatability of the nutritional ingredient or pharmaceutically active agent. Similarly, the pharmaceutically active ingredient may be incorporated into a novel drug delivery system, such as microspheres, microcapsules, liposomes, niosomes, nanoparticles, microemulsions, or nanoemulsions to protect the drug or permit organ targeting. Tn certain embodiments of the present invention, the rate of release of the active ingredient may be modulated or controlled by, for example, the use of controlled or sustained release agents (e.g., polymers) or by using excipients (e.g., disintegrants) that promote in rapid release, as appropriate.

[0075] In certain preferred embodiments, as provided in the Examples included hereinbelow, the soft-chew tablets formed by the inventive process exhibit a hardness of less than 2 kp when measured on a tablet hardness tester. In certain preferred embodiments, as provided in the Examples included hereinbelow, the soft-chew tablets formed by the inventive process exhibit a hardness of less than 1 kp when measured on a tablet hardness tester. In certain preferred embodiments, as provided in the Examples included hereinbelow, the soft-chew tablets formed by the inventive process exhibit no hardness when measured on a tablet hardness tester.

[0076] The measure of the mechanical integrity of tablets is their breaking force or hardness, which is the force required to cause them to fail (i.e., break) in a specific plane. Various equipment is used for hardness measurements, for example a Monsanto Hardness Tester, Stokes Hardness tester, Pfizer Hardness Tester, Strong-Cobb Hardness Tester, or Schleuniger Hardness tester. Tablet hardness can be expressed using various units depending on the equipment used for hardness measurement. Typical units for tablet hardness measurement are newtons, pounds, Strong-Cobb units, and kiloponds. In the Examples included hereinbelow, a Schleuniger Hardness tester was used, and the value for hardness was provided in kiloponds or newtons. This apparatus has two parallel platens between which a tablet is placed. A load is applied and the value of the hardness is measured. The platen faces are polished smooth and precision-ground perpendicularly to the direction of movement. Perpendicularity is preserved during platen movement, and the mechanism is free of any bending or torsion displacements as the load is applied. The contact faces are larger than the area of contact with the tablet.

[0077] As tablet hardness decreases, tablet friability generally increases. But the inventors hereof have unexpectedly found that for the formulations described herein, soft-chew tablets with hardness values of less than 2 kp, or lower, tablet friability remains less than 1%. In certain preferred embodiments, as provided in the Examples included hereinbelow, the soft-chew tablets formed by the inventive process exhibit a friability of less than about 1%, when measured in accordance with the USP friability test. In certain preferred embodiments, as provided in the Examples included hereinbelow, the soft-chew tablets formed by the inventive process exhibit a friability of less than about 0.5%, when measured in accordance with the USP friability test. Tn certain preferred embodiments, as provided in the Examples included hereinbelow, the soft-chew tablets formed by the inventive process exhibit a friability of less than about 0.5%, when measured in accordance with the USP friability test. In certain preferred embodiments, as provided in the Examples included hereinbelow, the soft-chew tablets formed by the inventive process exhibit a friability of less than about 0.1% at 100-rotations (in accordance with the USP friability test), 200- rotations, and even 300-rotations.

[0078] The soft-chew tablets formed by the inventive process, as provided in the Examples included hereinbelow, maintain a characteristic selected from chewiness, hardness, compression energy, adhesion, cohesiveness, springiness, and modulus, and any combination of any two or more thereof (when measured by the texture analyzer as described in the Examples included hereinbelow) sufficient to provide a chewable texture.

[0079] In certain preferred embodiments, the soft-chew tablets of the present invention have a weight (i.e., mass) between about 0.1 g and about 10 g. In certain embodiments, the soft-chew tablet of the present invention has a weight between about 0.5 g and about 4.0 g. In certain embodiments, the soft-chew tablet of the present invention has a weight between about 0.1 g and about 3.0 g. In certain embodiments, the soft-chew tablet of the present invention has a weight of about 0.1 g and about 2.0 g. In certain embodiments of the present invention, the weight of the soft-chew tablet can be between about 0.1 and about 1.0 g; between about 1.1 g and about 2.0 g; between about 2.1 g and about 3.0 g; between about 3.0 g and 3.1 g and about 4.0 g; or between about 4.1 g and about 5.0 g.

[0080] The soft-chew tablets of the present invention may have a wide range of weights, dimensions, and shapes to adapt to the need of the target patient population.

[0081] The soft-chew tablets of the present invention can be packaged in bulk primary packaging, or as singular unit primary packaging.

[0082] Certain aspects of the present invention relate to a tablet compression tooling that provides an anti-sticking means for tablet formulations that are sticky and/or necessarily moist, such as lubricated granules. In certain embodiments of the present invention, the tablet compression tool assembly includes an upper punch, a lower punch, and a die.

[0083] In certain embodiments of the present invention, such as those depicted in FIGS. 1-6, the tablet compression tool assembly 1 includes an upper punch 3a, a lower punch 3b, and a die 5. Each punch (3a, 3b) includes a head (7a, 7b), a neck (9a, 9b), a body (11 a, 11b), a stem (13a, 13b), and a punch tip (15a, 15b). The head (7a, 7b) includes a head flat, a head diameter, an outer head radius, and an under head angle. The neck (9a, 9b) is arranged adjacent the head (7a, 7b) and extends axially toward the body (Ila, lib) of the punch (3a, 3b). The body (Ila, 11b) typically includes one or more keyways to facilitate arrangement of the punch on the tablet compressing device. The stem (13a, 13b) projects axially from the punch body (Ila, 11b) and presents a receiver (17a, 17b) to facilitate arrangement of the punch tip (15a, 15b). One or more through holes 19 are located on the stem (13a, 13b), which align with complementary holes 21 in the body (23a, 23b) of the punch tip (15a, 15b) to facilitate fixed arrangement of the punch tip (15a, 15b) on the punch (3a, 3b) with fasteners 25. The punch tip (15a, 15b) includes a concave face (27a, 27b) presenting a cup depth. The face (27a, 27b) may include projections 29 to facilitate debossing numbers, letters, break lines, logos, and other designs into the surface of the tablet 31. The die 5 includes die faces 33 spaced-apart by a die body 35, an outer die radius, a die bore 37, and a bore insert (not shown) arranged within bore 37.

[0084] Compression tool assemblies of the present invention are not limited to the those depicted in FIGS. 1-6, and other compression tool assembly constructions are within the ambit of the present invention. For instance, in another preferred embodiment of the present invention, as shown in FIG. 7, the punch 201 includes a head 203, neck 205, body 207, and a punch tip 209. Punch tip 209 is arranged to body 207 with fasteners 213.

[0085] In the preferred embodiments, the punch tips and bore insert are formed from a polymer material having the following characteristics: low friction, self-cleaning, durable, resistant to a wide range of temperatures, non-flammable, corrosion resistant, and/or providing suitable electrical resistance. For instance, in certain embodiments of the present invention, the punch tips and bore insert are made from PTFE, POM, Nylon cast, and combinations of thereof. Polymer die bore insert helps reduce friction between die and punch tips, which reduces the formation of film within the die bore when wet granules are being compressed.

[0086] In other embodiments of the present invention, the punch tips and bore insert are made from POM, which is a high-performance acetal resin with several suitable physical and mechanical properties. POM is a highly-crystalline engineered thermoplastic that is widely regarded for its durability, stiffness, and exceptional dimensional stability. Suitable POM materials are marketed under the brand name Delrin®. [0087] POM sheet and rods come in many forms, filled and unfilled. In certain embodiments of the present invention, the punch tips and bore insert arc made from PTFE-fillcd copolymer Delrin, which provides outstanding durability. Often this copolymer material is used in the place of machined metal and plastics when good dimensional stability, minimal friction, and excellent resistance to wear are required. The PTFE-filled copolymer Delrin may be utilized under the present invention without any form of grease or lubricant. The white PTFE-filled copolymer Delrin complies with industry rules and regulations, such as those of the FDA.

[0088] In the preferred embodiments, as described in more detail in the Examples included hereinbelow, the compression force necessary to form the soft-chew tablets, of any shape and size, using polymer punch tips of the present invention is less than 4 kN, preferably less than 2 kN, and more preferably less than 1 kN.

[0089] In the trials where the polymer punch tips of the present invention were used, the occurrence of sticking/picking was greatly reduced relative to known anti-stick tooling assemblies. Tooling assemblies of the present invention enable, among other things, formation of compressed tablets from tablet formulations that are prone to sticking with a greatly reduced occurrence of sticking/picking .

[0090] Advantageously, soft-chew tablets formed in accordance with the present invention, among other things, may be packaged or further processed (e.g., tablet dusting or coating) immediately after compression, with no cure or hold time necessary.

[0091] Additional advantages of the various embodiments will be apparent to those skilled in the art upon review of the disclosure herein and the working examples below. It will be appreciated that the various embodiments described herein are not necessarily mutually exclusive unless otherwise indicated herein. For example, a feature described or depicted in one embodiment may also be included in other embodiments but is not necessarily included. Thus, the present disclosure encompasses a variety of combinations and/or integrations of the specific embodiments described herein.

EXAMPLES

[0092] The following working examples set forth preferred embodiments in accordance with the present invention. It is to be understood, however, that these examples are provided by way of illustration and nothing therein should be taken as a limitation upon the overall scope of the invention. [0093] Example 1 : A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 1 below. The ingredients corresponding to Example 1 are tabulated in Table 1 with the amount of each ingredient used in the process (i.e., the batch quantity) given in percent-by-weight (%w/w) and in milligrams. In Example 1, the active ingredients are phenylephrine HC1 and doxylamine succinate. Each soft-chew tablet formed by the process of Example 1 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of doxylamine succinate of about 12.5 mg. The amount of each ingredient provided in Table 1 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 1 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0094]

[0095] Procedure - Example 1

[0096] Step 1: The batch quantities of phenylephrine HC1 and doxylamine succinate were co-sifted using a No. 60 American Standard Test Sieve Series (ASTM).

[0097] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 60 ASTM and collected in a polybag.

[0098] Step 3: The batch quantities of sodium bicarbonate, flavor agent (tangerine), tingling flavor, calcium gluconate, bitter blocker, and carboxymethylcellulose calcium, along with about 77% of the batch quantity of sucralose, about 53% of the batch quantity of carnauba wax, and the sifted material of step 2, were sifted with a No. 30 ASTM.

[0099] Step 4: The sifted ingredients of Step 3 were sifted a second time with a No. 30 ASTM and collected in a polybag.

[0100] Step 5: The batch quantities of dried glucose syrup, croscarmellose sodium, and sorbitol powder, along with about 81% of the batch quantity of milk powder, about 60% of the batch quantity of mannitol, and the sifted material of Step 4, were co-sifted using a No. 30 ASTM.

[0101] Step 6: The sifted ingredients of Step 5 were sifted a second time with a No. 30 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0102] Step 7: The batch quantities of flavor agent (honey) and crospovidone, along with the remaining batch quantities of mannitol and milk powder, were co-sifted with a No. 30 ASTM.

[0103] Step 8: The sifted ingredients of Step 7 were sifted a second time with a No. 30 ASTM to form an extragranular ingredient mixture, which was collected in a polybag.

[0104] Step 9: The remaining batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag.

[0105] Step 10: The batch quantity of pure honey was added to the batch quantity of glycerin under continuous stirring.

[0106] Step 11: The batch quantity of color agent was added to the mixture of Step 10 under continuous stirring.

[0107] Step 12: The batch quantity of flavor agent (vanilla), along with the remaining batch quantity of sucralose, were added to the mixture of Step 11 under continuous stirring.

[0108] Step 13: The mixture of Step 12 was stirred until a uniform dispersion was formed.

[0109] Step 14: The intragranular ingredient mixture of Step 6 was transferred to a rapid mixer granulator (with the impeller set to a slow speed and the chopper off) and mixed for approximately 10-minutes.

[0110] Step 15: The batch quantity of polyethylene glycol was slowly added to the mixture of Step 14 in a thin stream (with the impeller set to a slow speed and the chopper on) with intermittent racking.

[0111] Step 16: The uniform dispersion of Step 13 was slowly added to the mixture of Step 15 in a thin stream (with the impeller set to a slow speed and the chopper on) with intermittent racking to form a wet mass. [0112] Step 17: The extragranular ingredient mixture of Step 8 was slowly added to the wet mass of Step 16 under continuous mixing (with the impeller set to a slow speed and the chopper on), and the discharged material was collected on a tray.

[0113] Step 18: The material of Step 17 was passed through a cone mill to form milled granules. The cone mill was fitted with a 3mm screen, the knife was in the forward position, and the speed setting was slow.

[0114] Step 19: The wet granules of Step 18 were lubricated using the material of Step 9 for approximately 2-minutes.

[0115] Step 20: The wet granules from Step 19 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) polytetrafluoroethylene (“PTFE”) punch tip (length not less than 2.00 mm), with one of the punch tips having the letter “R” embossed on one side.

[0116] Step 21: The tablet from Step 20 was coated using the batch quantity of fine sugar.

[0117] Example 2: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 2 below. The ingredients corresponding to Example 2 are tabulated in Table 2 with the amount of each ingredient used in the process given in percent- by-weight and in milligrams. In Example 2, the active ingredients are phenylephrine HC1 and doxylamine succinate. Each soft-chew tablet formed by the process of Example 2 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of doxylamine succinate of about 12.5 mg. The amount of each ingredient provided in Table 2 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 2 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0118]

[0119] Procedure - Example 2

[0120] Step 1: The batch quantities of doxylamine succinate and sodium gluconate, along with about 69% of the batch quantity of sucralose and about 45% of the batch quantity of flavor agent (honey), were co-sifted using a No. 40 ASTM.

[0121 ] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 40 ASTM and collected in a polybag.

[0122] Step 3: The batch quantities of maltodextrin, sorbitol powder, croscarmellose sodium, mannitol, and corn starch, along with the sifted ingredients of Step 2, were co-sifted using a No. 40 ASTM.

[0123] Step 4: The sifted ingredients of Step 3 were sifted a second time with a No. 40 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0124] Step 5: The batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag.

[0125] Step 6: The batch quantity of propyl gallate was added to the batch quantity of propylene glycol under continuous stirring.

[0126] Step 7: The batch quantity of phenylephrine HC1 was added to the batch quantity of glycerin under continuous stirring.

[0127] Step 8: The material of Step 6 was added to the material of Step 7 under continuous stirring. [0128] Step 9: The batch quantities of color agent and flavor agent (menthol), along with the remaining batch quantities of sucralose and flavor agent (honey), were added to the mixture of Step 8 under continuous stirring.

[0129] Step 10: The mixture of Step 9 was stirred until a uniform dispersion was formed.

[0130] Step 11: The intragranular ingredient mixture of Step 4 was mixed for approximately 4- minutes.

[0131] Step 12: The uniform dispersion of Step 10 was slowly added to the mixture of Step 11 under continuous mixing to form uniform wet granules.

[0132] Step 13: The wet granules of Step 12 were sifted using a No. 8 ASTM and collected in a tray.

[0133] Step 14: The wet granules of Step 13 were lubricated using the material of Step 5 for approximately 2-minutes.

[0134] Step 15: The wet granules from Step 14 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) PTFE punch tip, with one of the punch tips having the letter “T” embossed on one side, to form a compressed tablet.

[0135] Step 16: The tablet from Step 15 was coated using the batch quantity of sucrose.

[0136] Example 3: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 3 below. The ingredients corresponding to Example 3 are tabulated in Table 3 with the amount of each ingredient used in the process given in percent- by-weight and in milligrams. In Example 3, the active ingredients are phenylephrine HC1 and doxylamine succinate. Each soft-chew tablet formed by the process of Example 3 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of doxylamine succinate of about 12.5 mg. The amount of each ingredient provided in Table 3 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 3 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets. [0137]

[0138] Procedure - Example 3

[0139] Step 1: The batch quantity of doxylamine succinate was added to the batch quantity of acetone under continuous stirring.

[0140] Step 2: The batch quantities of amino methacrylate copolymer, calcium gluconate, and magnesium oxide, along with about 35% of the batch quantity of sucralose, were added to the mixture of Step 1 under continuous stirring.

[0141] Step 3: The material of Step 2 was kept for drying.

[0142] Step 4: The dried material of Step 3 was sifted using a No. 40 ASTM and collected in a container. [0143] Step 5: The batch quantities of guar gum, mannitol, glucidex IT 12, croscarmellose sodium, and monoammonium glycyrrhizinatc, along with about 49% of the batch quantity of carnauba wax, about 67% of the batch quantity of sodium bicarbonate, about 45% of the batch quantity of flavor agent (honey), and the material of Step 4, were co-sifted using a No. 30 ASTM.

[0144] Step 6: The sifted ingredients of Step 5 were sifted a second time with a No. 30 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0145] Step 7: The remaining batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag.

[0146] Step 8: The batch quantity of sorbitol solution was added to the batch quantity of glycerin under continuous stirring.

[0147] Step 9: The batch quantity of color agent was added to the mixture of Step 8 under continuous stirring.

[0148] Step 10: The batch quantities of sodium gluconate, citric acid anhydrous, and flavor agent (menthol), along with the remaining batch quantities of sucralose and flavor agent (honey), were added to the mixture of Step 9 under continuous stirring.

[0149] Step 11: The mixture of Step 10 was stirred until a uniform dispersion was formed.

[0150] Step 12: The intragranular ingredient mixture of Step 6 was mixed for approximately 2- minutes.

[0151] Step 13: The uniform dispersion of Step 11 was slowly added to the mixture of Step 12 under continuous mixing to form uniform wet granules.

[0152] Step 14: The wet granules of Step 13 were sifted using a No. 8 ASTM and collected in a tray.

[0153] Step 15: The wet granules of Step 14 were lubricated using the material of Step 7 for approximately 2-minutes.

[0154] Step 16: The batch quantity of phenylephrine HC1 (coated) was added to the granules of Step 15 under continuous mixing for approximately 2-minutes.

[0155] Step 17: The wet granules from Step 16 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) PTFE punch tip, with one of the punch tips having the letter “T” embossed on one side, to form a compressed tablet. [0156] Step 18: The tablet from Step 17 was sprinkled using the batch quantity of sucrose and the remaining batch quantity of sodium bicarbonate.

[0157] Example 4: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 4 below. The ingredients corresponding to Example 4 are tabulated in Table 4 with the amount of each ingredient used in the process given in percent- by-weight and in milligrams. In Example 4, the active ingredients are phenylephrine HC1 and doxylamine succinate. Each soft-chew tablet formed by the process of Example 4 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of doxylamine succinate of about 12.5 mg. The amount of each ingredient provided in Table 4 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 4 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0158]

[0159] Procedure - Example 4

[0160] Step 1: The batch quantities of doxylamine succinate and phenylephrine HC1 were added to the batch quantity of acetone under continuous stirring.

[0161] Step 2: The batch quantities of amino methacrylate copolymer and magnesium oxide, along with about 48% of the batch quantity of sucralose and about 29% of the batch quantity of flavor agent (honey), were added to the mixture of Step 1 under continuous stirring.

[0162] Step 3: The material of Step 2 was kept for drying.

[0163] Step 4: The dried material of Step 3 was sifted using a No. 40 ASTM and collected in a container. [0164] Step 5: The batch quantities of dried glucose syrup, croscarmellose sodium, and sorbitol powder, along with about 50% of the batch quantity of carnauba wax, about 57% of the batch quantity of mannitol, about 74% of the batch quantity of milk powder, and the sifted ingredients of Step 4, were co-sifted using a No. 30 ASTM.

[0165] Step 6: The sifted ingredients of Step 5 were sifted a second time with a No. 30 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0166] Step 7: The batch quantity of crospovidone, along with the remaining batch quantities of milk powder and mannitol, and about 29% of the batch quantity of flavor agent (honey), were cosifted with a No. 30 ASTM.

[0167] Step 8: The sifted ingredients of Step 7 were sifted a second time with a No. 30 ASTM to form an extragranular ingredient mixture, which was collected in a polybag.

[0168] Step 9: The remaining batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag.

[0169] Step 10: The batch quantity of sorbitol solution was added to the batch quantity of glycerin under continuous stirring.

[0170] Step 11: The batch quantity of color agent was added to the material of Step 10 under continuous stirring.

[0171] Step 12: The batch quantity of flavor agent (menthol), along with the remaining batch quantities of flavor agent (honey) and sucralose, were added to the mixture of Step 9 under continuous stirring.

[0172] Step 13: The mixture of Step 12 was stirred until a uniform dispersion was formed.

[0173] Step 14: The intragranular ingredient mixture of Step 6 was mixed for approximately 2- minutes.

[0174] Step 15: The batch quantity of propylene glycol was slowly added to the mixture of Step 14 in a thin stream with intermittent racking.

[0175] Step 16: The uniform dispersion of Step 13 was slowly added to the mixture of Step 15 under continuous mixing to form a wet mass.

[0176] Step 17: The extragranular ingredient mixture of Step 8 was slowly added to the wet mass of Step 16 under continuous mixing.

[0177] Step 18: The wet granules of Step 17 were sifted using a No. 8 ASTM and collected in a tray. [0178] Step 19: The wet granules of Step 18 were lubricated using the material of Step 9 for approximately 2-minutcs.

[0179] Step 20: The wet granules from Step 19 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 18mm) PTFE punch tip to form a compressed tablet.

[0180] Step 21: The tablet from Step 20 was sprinkle coated using the batch quantity of fine sugar. [0181] Example 5: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 5 below. The ingredients corresponding to Example 5 are tabulated in Table 5 with the amount of each ingredient used in the process given in percent- by-weight and in milligrams. In Example 5, the active ingredients are phenylephrine HC1 and doxylamine succinate. Each soft-chew tablet formed by the process of Example 5 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of doxylamine succinate of about 12.5 mg. The amount of each ingredient provided in Table 5 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 5 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0182]

[0183] Procedure - Example 5

[0184] Step 1: The batch quantities of maltodextrin, croscarmellose sodium, guar gum, and monoammonium glycyrrhizinate, along with about 71% of the batch quantity of mannitol and about 45% of the batch quantity of flavor agent (honey), were co-sifted using a No. 40 ASTM.

[0185] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 40 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0186] Step 3: The remaining batch quantity of mannitol was sifted with a No. 40 ASTM and collected in a polybag.

[0187] Step 4: About 57% of the batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag. [0188] Step 5: The batch quantities of doxylamine succinate and sodium gluconate, along with the remaining batch quantity of carnauba wax, about 77% of the batch quantity of sucralose, and about 67% of the batch quantity of bitter blocker, were co-sifted using a No. 80 ASTM.

[0189] Step 6: The sifted ingredients of Step 5 were sifted a second time with a No. 80 ASTM and collected in a polybag.

[0190] Step 7: The batch quantity of propyl gallate was added to the batch quantity of propylene glycol under continuous stirring.

[0191] Step 8: The batch quantity of sorbitol solution was added to the batch quantity of glycerin under continuous stirring.

[0192] Step 9: The material of Step 7 was added to the material of Step 8 under continuous stirring. [0193] Step 10: The batch quantity of phenylephrine HC1 was added to the material of Step 9 under continuous stirring.

[0194] Step 11: The batch quantity of color agent was added to the material of Step 10 under continuous stirring.

[0195] Step 12: The batch quantity of flavor agent (menthol), along with the remaining batch quantities of flavor agent (honey), sucralose, and bitter blocker, were added to the mixture of Step 11 under continuous stirring.

[0196] Step 13: The mixture of Step 12 was stirred until a uniform dispersion was formed.

[0197] Step 14: The intragranular ingredient mixture of Step 2 was mixed for approximately 2- minutes.

[0198] Step 15: The uniform dispersion of Step 13 was slowly added to the mixture of Step 14 under continuous mixing to form a wet mass.

[0199] Step 16: The wet mass of Step 15 along with the sifted material of Step 3 were co-sifted using a No. 8 ASTM to form wet granules.

[0200] Step 17: The wet granules of Step 16 were lubricated using the material of Step 4 for approximately 2-minutes.

[0201] Step 18: The mixture of Step 6 was added to the granules of Step 17 and mixed uniformly. [0202] Step 19: The wet granules from Step 18 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) POM punch tip, with one of the punch tips having the letter “T” embossed on one side, with a compression force of 1 kN to form a compressed tablet. [0203] Step 20: The tablet from Step 19 was sprinkle coated using the batch quantities of sodium bicarbonate and sucrose.

[0204] Example 6: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 6 below. The ingredients corresponding to Example 6 are tabulated in Table 6 with the amount of each ingredient used in the process given in percent- by-weight and in milligrams. In Example 6, the active ingredients are phenylephrine HC1 and doxylamine succinate. Each soft-chew tablet formed by the process of Example 6 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of doxylamine succinate of about 12.5 mg. The amount of each ingredient provided in Table 6 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 6 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0205]

[0206] Procedure - Example 6

[0207] Step 1: The batch quantities of croscarmellose sodium, partially pregelatinized starch, monoammonium glycyrrhizinate, and sorbitol powder, along with about 86% of the batch quantity of maltodextrin, about 58% of the batch quantity of mannitol, and about 29% of the batch quantity of flavor agent (honey), were co-sifted using a No. 40 ASTM.

[0208] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 40 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0209] Step 3: The remaining batch quantity of mannitol was sifted with a No. 40 ASTM and collected in a polybag. [0210] Step 4: About 57% of the batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag.

[0211] Step 5: The batch quantities of doxylamine succinate and sodium gluconate, along with the remaining batch quantity of carnauba wax, the remaining batch quantity of maltodextrin, about 35% of the batch quantity of flavor agent (honey), about 27% of the batch quantity of neotame, and about 67% of the batch quantity of bitter blocker, were co-sifted using a No. 80 ASTM.

[0212] Step 6: The sifted ingredients of Step 5 were sifted a second time with a No. 80 ASTM and collected in a polybag.

[0213] Step 7: The batch quantity of propyl gallate was added to the batch quantity of propylene glycol under continuous stirring.

[0214] Step 8: The batch quantity of sorbitol solution was added to the batch quantity of glycerin under continuous stirring.

[0215] Step 9: The material of Step 7 was added to the material of Step 8 under continuous stirring. [0216] Step 10: The batch quantity of phenylephrine HC1 was added to the material of Step 9 under continuous stirring.

[0217] Step 11: The batch quantity of color agent was added to the material of Step 10 under continuous stirring.

[0218] Step 12: The batch quantity of flavor agent (menthol), along with the remaining batch quantities of flavor agent (honey), neotame, and bitter blocker, were added to the mixture of Step 11 under continuous stirring.

[0219] Step 13: The mixture of Step 12 was stirred until a uniform dispersion was formed.

[0220] Step 14: The intragranular ingredient mixture of Step 2 was mixed for approximately 2- minutes.

[0221] Step 15: The uniform dispersion of Step 13 was slowly added to the mixture of Step 14 under continuous mixing to form a wet mass.

[0222] Step 16: The wet mass of Step 15 along with the sifted material of Step 3 were co-sifted using a No. 8 ASTM to form wet granules.

[0223] Step 17: The wet granules of Step 16 were lubricated using the material of Step 4 for approximately 2-minutes.

[0224] Step 18: The mixture of Step 6 was added to the granules of Step 17 and mixed uniformly. [0225] Step 19: The wet granules from Step 18 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) PTFE punch tip, with one of the punch tips having the letter “T” embossed on one side, to form a compressed tablet.

[0226] Step 20: The tablet from Step 19 was sprinkle coated using the batch quantities of sodium bicarbonate and sucrose.

[0227] Example 7: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 7 below. The ingredients corresponding to Example 7 are tabulated in Table 7 with the amount of each ingredient used in the process given in percent- by-weight and in milligrams. In Example 7, the active ingredients are phenylephrine HC1 and doxylamine succinate. Each soft-chew tablet formed by the process of Example 7 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of doxylamine succinate of about 12.5 mg. The amount of each ingredient provided in Table 7 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 7 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0228]

[0229] Procedure - Example 7

[0230] Step 1: The batch quantities of sorbitol powder, milk powder, croscarmellose sodium, mannitol, partially pregelatinized starch, and flavor agent (honey) were co-sifted using a No. 40 ASTM.

[0231] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 40 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0232] Step 3: The batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag. [0233] Step 4: The batch quantities of propyl gallate and BHA were added to the batch quantity of propylene glycol under continuous stirring.

[0234] Step 5: The batch quantity of BHT was added to the batch quantity of light mineral oil under continuous stirring.

[0235] Step 6: The batch quantity of maltitol solution was added to the batch quantity of glycerin under continuous stirring.

[0236] Step 7: The material of Step 4 and the material of Step 5 were slowly added to the material of Step 6 under continuous stirring.

[0237] Step 8: The batch quantity of color agent was added to the material of Step 7 under continuous stirring.

[0238] Step 9: The batch quantities of phenylephrine HC1, doxylamine succinate, sodium gluconate, neotame, flavor agent (menthol), and edetate disodium were added to the mixture of Step 8 under continuous stirring.

[0239] Step 10: The mixture of Step 9 was stirred until a uniform dispersion was formed.

[0240] Step 11: The intragranular ingredient mixture of Step 2 was mixed for approximately 2- minutes.

[0241] Step 12: The uniform dispersion of Step 10 was slowly added to the mixture of Step 11 under continuous mixing to form a wet mass.

[0242] Step 13: The wet mass of Step 12 was sifted using a No. 8 ASTM to form wet granules, which were collected in a tray.

[0243] Step 14: The wet granules of Step 13 were lubricated using the material of Step 3 for approximately 2-minutes.

[0244] Step 15: The wet granules from Step 14 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) PTFE punch tip, with one of the punch tips having the letter “T” embossed on one side, to form a compressed tablet.

[0245] Step 16: The tablet from Step 15 was sprinkle coated using the batch quantity of sodium bicarbonate.

[0246] Example 8: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 8 below. The ingredients corresponding to Example 8 are tabulated in Table 8 with the amount of each ingredient used in the process given in percent- by-weight and in milligrams. Tn Example 8, the active ingredients are phenylephrine HC1 and doxylaminc succinate. Each soft-chew tablet formed by the process of Example 8 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of doxylamine succinate of about 12.5 mg. The amount of each ingredient provided in Table 8 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 8 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0247]

[0248] Procedure - Example 8

[0249] Step 1: The batch quantities of sorbitol powder, maltodextrin, croscarmellose sodium, mannitol, partially pregelatinized starch, and flavor agent (honey) were co-sifted using a No. 40 ASTM.

[0250] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 40 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0251] Step 3: The batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag. [0252] Step 4: The batch quantities of propyl gallate and BHA were added to the batch quantity of propylene glycol under continuous stirring.

[0253] Step 5: The batch quantity of BHT was added to the batch quantity of light mineral oil under continuous stirring.

[0254] Step 6: The batch quantities of phenylephrine HC1 and doxylamine succinate were added to the batch quantity of maltitol solution under continuous stirring.

[0255] Step 7: The material of Step 4 and the material of Step 5 were slowly added to the material of Step 6 under continuous stirring.

[0256] Step 8: The batch quantity of color agent was added to the material of Step 7 under continuous stirring.

[0257] Step 9: The batch quantities of neotame, flavor agent (menthol), sodium gluconate, edetate disodium, and bitter blocker were added to the mixture of Step 8 under continuous stirring.

[0258] Step 10: The mixture of Step 9 was stirred until a uniform dispersion was formed.

[0259] Step 11: The intragranular ingredient mixture of Step 2 was mixed for approximately 2- minutes.

[0260] Step 12: The uniform dispersion of Step 10 was slowly added to the mixture of Step 11 under continuous mixing to form a wet mass.

[0261] Step 13: The wet mass of Step 12 was sifted using a No. 8 ASTM to form wet granules, which were collected in a tray.

[0262] Step 14: The wet granules of Step 13 were lubricated using the material of Step 3 for approximately 2-minutes.

[0263] Step 15: The wet granules from Step 14 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) PTFE punch tip, with one of the punch tips having the letter “T” embossed on one side, to form a compressed tablet.

[0264] Step 16: The tablet from Step 15 was sprinkle coated using the batch quantity of sodium bicarbonate.

[0265] Example 9: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 9 below. The ingredients corresponding to Example 9 are tabulated in Table 9 with the amount of each ingredient used in the process given in percent- by-weight and in milligrams. In Example 9, the active ingredients are phenylephrine HC1 and doxylamine succinate. Each soft-chew tablet formed by the process of Example 9 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of doxylamine succinate of about 12.5 mg. The amount of each ingredient provided in Table 9 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 9 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0266]

[0267] Procedure - Example 9

[0268] Step 1: The batch quantities of bitter blocker, calcium gluconate monohydrate, color agent, croscarmellose sodium, doxylamine succinate, dried glucose syrup, phenylephrine HC1 (coated), and sodium bicarbonate, along with about 14% of the batch quantity of flavor agent (honey), about 50% of the batch quantity of carnauba wax, about 57% of the batch quantity of mannitol, about 73% of the batch quantity of milk powder, and about 75% of the batch quantity of sucralose, were co-sifted using a No. 30 ASTM.

[0269] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 30 ASTM to form an intragranular ingredient mixture, which was collected in a polybag. [0270] Step 3: The batch quantity of crospovidone, along with the remaining batch quantities of milk powder and mannitol, and about 43% of the batch quantity of flavor agent (honey), were cosifted with a No. 30 ASTM.

[0271] Step 4: The sifted ingredients of Step 3 were sifted a second time with a No. 30 ASTM to form an extragranular ingredient mixture, which was collected in a polybag.

[0272] Step 5: The remaining batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag.

[0273] Step 6: The batch quantity of sorbitol solution was added to the batch quantity of glycerin under continuous stirring.

[0274] Step 7: The batch quantity of flavor agent (menthol freeze) was added to the mixture of Step 6 under continuous stirring.

[0275] Step 8: The remaining batch quantities of flavor agent (honey) and sucralose were added to the mixture of Step 7 under continuous stirring.

[0276] Step 9: The mixture of Step 8 was stirred until a uniform dispersion was formed.

[0277] Step 10: The intragranular ingredient mixture of Step 2 was transferred to a rapid mixer granulator (with the impeller set to a slow speed and the chopper off) and mixed for approximately 10-minutes.

[0278] Step 11: The batch quantity of propylene glycol was slowly added to the mixture of Step 10 in a thin stream under continuous mixing (with the impeller set to a slow speed and the chopper on) with intermittent racking.

[0279] Step 12: The uniform dispersion of Step 9 was slowly added to the mixture of Step 11 in a thin stream (with the impeller set to a slow speed and the chopper on) with intermittent racking to form a wet mass.

[0280] Step 13: The wet mass of Step 12, along with about 75% of the extragranular ingredient mixture of Step 4, was passed through a cone mill to form milled wet granules. The cone mill was fitted with a 4mm screen, the knife was in the forward position, and the speed setting was slow.

[0281] Step 14: The wet granules of Step 13, along with the remaining extragranular ingredient mixture of Step 4, were co-sifted with a No. 8 ASTM.

[0282] Step 15: The wet granules of Step 14 were sifted a second time using a No. 8 ASTM and collected in a polybag. [0283] Step 16: The wet granules of Step 15 were lubricated using the material of Step 5 for approximately 2-minutcs.

[0284] Step 17: The wet granules from Step 16 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 18mm) PTFE punch tip, with a compression force of 4 kN, to form a compressed tablet to form a compressed tablet.

[0285] Step 18: The tablet from Step 17 was sprinkle coated using the batch quantity of fine sugar. [0286] Example 10: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 10 below. The ingredients corresponding to Example 10 are tabulated in Table 10 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 10, the active ingredients are phenylephrine HC1 and doxylamine succinate. Each soft-chew tablet formed by the process of Example 10 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of doxylamine succinate of about 12.5 mg. The amount of each ingredient provided in Table 10 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 10 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0287]

[0288] Procedure - Example 10

[0289] Step 1: The batch quantities of bitter blocker, calcium gluconate monohydrate, croscarmellose sodium, doxylamine succinate, dried glucose syrup, flavor agent (vanilla), phenylephrine HC1, sodium bicarbonate, and sorbitol powder, along with about 33% of the batch quantity of flavor agent (honey), about 50% of the batch quantity of carnauba wax, about 60% of the batch quantity of mannitol, about 73% of the batch quantity of milk powder, and about 75% of the batch quantity of sucralose, were co-sifted using a No. 30 ASTM.

[0290] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 30 ASTM to form an intragranular ingredient mixture, which was collected in a polybag. [0291 ] Step 3: The batch quantity of crospovidone, along with the remaining batch quantities of milk powder and mannitol, and about 27% of the batch quantity of flavor agent (honey), were cosifted with a No. 30 ASTM.

[0292] Step 4: The sifted ingredients of Step 3 were sifted a second time with a No. 30 ASTM to form an extragranular ingredient mixture, which was collected in a polybag.

[0293] Step 5: The remaining batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag.

[0294] Step 6: The batch quantity of sorbitol solution was added to the batch quantity of glycerin under continuous stirring.

[0295] Step 7: The batch quantity of color agent was added to the mixture of Step 6 under continuous stirring.

[0296] Step 8: The remaining batch quantities of flavor agent (honey) and sucralose, along with the batch quantity of flavor agent (menthol freeze), were added to the mixture of Step 7 under continuous stirring.

[0297] Step 9: The mixture of Step 8 was stirred until a uniform dispersion was formed.

[0298] Step 10: The intragranular ingredient mixture of Step 2 was transferred to a rapid mixer granulator (with the impeller set to a slow speed and the chopper off) and mixed for approximately 10-minutes.

[0299] Step 11: The batch quantity of propylene glycol was slowly added to the mixture of Step 10 in a thin stream under continuous mixing (with the impeller set to a slow speed and the chopper on) with intermittent racking.

[0300] Step 12: The uniform dispersion of Step 9 was slowly added to the mixture of Step 11 in a thin stream (with the impeller set to a slow speed and the chopper on) with intermittent racking to form a wet mass.

[0301] Step 13: The wet mass of Step 12, along with about 75% of the extragranular ingredient mixture of Step 4, were passed through a cone mill to form milled granules. The cone mill was fitted with a 3mm screen, the knife was in the forward position, and the speed setting was slow.

[0302] Step 14: The granules of Step 13, along with the remaining extragranular ingredient mixture of Step 4, were co-sifted with a No. 8 ASTM.

[0303] Step 15: The wet granules of Step 14 were sifted a second time using a No. 8 ASTM and collected in a polybag. [0304] Step 16: The wet granules of Step 15 were lubricated using the material of Step 5 for approximately 2-minutcs.

[0305] Step 17: The wet granules from Step 16 were compressed using a rotary tablet press equipped with upper and lower punches, each including a round-shaped (diameter of approx. 18mm) POM punch tip (length not less than 2.00 mm), and a die with a POM die bore insert, to form a compressed tablet.

[0306] Step 18: The tablet from Step 17 was sprinkle coated using the batch quantity of fine sugar. [0307] Example 11: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 11 below. The ingredients corresponding to Example 11 are tabulated in Table 11 with the amount of each ingredient used in the process given in percent- by-weight and in milligrams. In Example 11, the active ingredients are phenylephrine HC1 and doxylamine succinate. Each soft-chew tablet formed by the process of Example 11 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of doxylamine succinate of about 12.5 mg. The amount of each ingredient provided in Table 11 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 11 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0308]

[0309] Procedure - Example 11

[0310] Step 1: The batch quantities of croscarmellose sodium, doxylamine succinate, mannitol, phenylephrine HC1 (coated), sodium gluconate, and sorbitol powder, along with about 45% of the batch quantity of flavor agent (honey) and about 69% of the batch quantity of sucralose, were cosifted using a No. 30 ASTM.

[0311] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 30 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0312] Step 3: The batch quantity of stearic acid was sifted using a No. 60 ASTM and collected in a polybag.

[0313] Step 4: The batch quantities of BHA, BHT, and edetate disodium were added to the batch quantity of maltitol solution under continuous stirring.

[0314] Step 5: The batch quantity of color agent was added to the mixture of Step 4 under continuous stirring. [0315] Step 6: The remaining batch quantities of flavor agent (honey) and sucralose, along with the batch quantity of flavor agent (menthol freeze), were added to the mixture of Step 5 under continuous stirring.

[0316] Step 7: The mixture of Step 6 was stirred until a uniform dispersion was formed.

[0317] Step 8: The intragranular ingredient mixture of Step 2 was mixed for approximately 2- minutes.

[0318] Step 9: The uniform dispersion of Step 7 was slowly added to the mixture of Step 8 under continuous mixing to form a wet mass.

[0319] Step 10: The wet mass of Step 9 was sifted using a No. 8 ASTM to form wet granules, which were collected in a tray.

[0320] Step 11: The wet granules of Step 10 were lubricated using the material of Step 3 for approximately 2-minutes.

[0321] Step 12: The wet granules from Step 11 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 18mm) PTFE punch tip to form a compressed tablet.

[0322] Step 13: The tablet from Step 12 was sprinkle coated using the batch quantity of fine sugar. [0323] Example 12: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 12 below. The ingredients corresponding to Example 12 are tabulated in Table 12 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 12, the active ingredients are phenylephrine HC1 and doxylamine succinate. Each soft-chew tablet formed by the process of Example 12 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of doxylamine succinate of about 12.5 mg. The amount of each ingredient provided in Table 12 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 12 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0324]

[0325] Procedure - Example 12

[0326] Step 1: The batch quantities of croscarmellose sodium, doxylamine succinate, mannitol, phenylephrine HC1, sodium gluconate, and sorbitol powder, along with about 69% of the batch quantity of sucralose and about 45% of the batch quantity of flavor agent (honey), were co-sifted using a No. 30 ASTM.

[0327] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 30 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0328] Step 3: The batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag.

[0329] Step 4: The batch quantities of BHA, BHT, and edetate disodium were added to the batch quantity of maltitol solution under continuous stirring.

[0330] Step 5: The batch quantity of color agent was added to the mixture of Step 4 under continuous stirring.

[0331] Step 6: The remaining batch quantities of flavor agent (honey) and sucralose, along with the batch quantity of flavor agent (menthol freeze), were added to the mixture of Step 5 under continuous stirring.

[0332] Step 7: The mixture of Step 6 was stirred until a uniform dispersion was formed. [0333] Step 8: The intragranular ingredient mixture of Step 2 was mixed for approximately 2- minutcs.

[0334] Step 9: The uniform dispersion of Step 7 was slowly added to the mixture of Step 8 under continuous mixing to form a wet mass.

[0335] Step 10: The wet mass of Step 9 was sifted using a No. 8 ASTM to form wet granules, which were collected in a tray.

[0336] Step 11: The wet granules of Step 10 were lubricated using the material of Step 3 for approximately 2-minutes.

[0337] Step 12: The wet granules from Step 11 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) PTFE punch tip, with one of the punch tips having the letter “T” embossed on one side, to form a compressed tablet.

[0338] Step 13: The tablet from Step 12 was sprinkle coated using the batch quantity of fine sugar. [0339] Example 13: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 13 below. The ingredients corresponding to Example 13 are tabulated in Table 13 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 13, the active ingredients are phenylephrine HC1 and brompheniramine maleate. Each soft-chew tablet formed by the process of Example 13 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of brompheniramine maleate of about 4.0 mg. The amount of each ingredient provided in Table 13 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 13 can be used to make more soft- chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0340]

[0341] Procedure - Example 13

[0342] Step 1: The batch quantities of phenylephrine HC1 and brompheniramine maleate were cosifted using a No. 60 ASTM.

[0343] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 60 ASTM and collected in a polybag.

[0344] Step 3: The batch quantities of sodium bicarbonate, flavor agent (tangerine), tingling flavor, calcium gluconate, bitter blocker, carboxymethylcellulose calcium, and monoammonium glycyrrhizinate, along with about 92% of the batch quantity of sucralose, about 43% of the batch quantity of carnauba wax, and the sifted material of Step 2, were co-sifted using a No. 30 ASTM. [0345] Step 4: The sifted ingredients of Step 3 were sifted a second time with a No. 30 ASTM and collected in a polybag.

[0346] Step 5: The batch quantities of dried glucose syrup, croscarmellose sodium, and sorbitol powder, along with about 77% of the batch quantity of milk powder, about 66% of the batch quantity of mannitol, and the sifted material of Step 4, were co-sifted using a No. 30 ASTM. [0347] Step 6: The sifted ingredients of Step 5 were sifted a second time with a No. 30 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0348] Step 7: The batch quantity of crospovidone, along with the remaining batch quantities of mannitol, milk powder, and about 38% of the batch quantity of flavor agent (mixed berry), were co- sifted with a No. 30 ASTM.

[0349] Step 8: The sifted ingredients of Step 7 were sifted a second time with a No. 30 ASTM to form an extragranular ingredient mixture, which was collected in a polybag.

[0350] Step 9: The remaining batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag.

[0351] Step 10: The batch quantity of maltitol solution was added to the batch quantity of glycerin under continuous stirring.

[0352] Step 11: The batch quantity of color agent was added to the mixture of Step 10 under continuous stirring.

[0353] Step 12: The remaining batch quantities of flavor agent (mixed berry) and sucralose, along with the batch quantity of citric acid anhydrous, were added to the mixture of Step 11 under continuous stirring.

[0354] Step 13: The mixture of Step 12 was stirred until a uniform dispersion was formed.

[0355] Step 14: The intragranular ingredient mixture of Step 6 was transferred to a rapid mixer granulator (with the impeller set to a slow speed and the chopper off) and mixed for approximately 10-minutes.

[0356] Step 15: The batch quantity of polyethylene glycol was slowly added to the mixture of Step 14 in a thin stream under continuous mixing (with the impeller set to a slow speed and the chopper on) with intermittent racking.

[0357] Step 16: The uniform dispersion of Step 13 was slowly added to the mixture of Step 15 in a thin stream (with the impeller set to a slow speed and the chopper on) with intermittent racking to form a wet mass.

[0358] Step 17: The extragranular ingredient mixture of Step 8 was slowly added to the wet mass of Step 16 under continuous mixing.

[0359] Step 18: The material of Step 17 was passed through a cone mill to form milled wet granules. The cone mill was fitted with a 3mm screen, the knife was in the forward position, and the speed setting was slow. [0360] Step 19: The wet granules of Step 18 were lubricated using the material of Step 9 for approximately 2-minutcs.

[0361] Step 20: The wet granules from Step 19 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 13mm) PTFE punch tip to form a compressed tablet.

[0362] Step 21: The tablet from Step 20 was sprinkle coated using the batch quantity of fine sugar. [0363] Example 14: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 14 below. The ingredients corresponding to Example 14 are tabulated in Table 14 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 14, the active ingredients are phenylephrine HC1 and brompheniramine maleate. Each soft-chew tablet formed by the process of Example 14 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of brompheniramine maleate of about 4.0 mg. The amount of each ingredient provided in Table 14 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 14 can be used to make more soft- chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0364]

[0365] Procedure - Example 14

[0366] Step 1: The batch quantities of brompheniramine maleate, phenylephrine HC1 (coated), sodium bicarbonate, calcium gluconate, and bitter blocker, along with about 90% of the batch quantity of sucralose, were co-sifted using a No. 30 ASTM.

[0367] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 30 ASTM and collected in a polybag.

[0368] Step 3: The batch quantities of dried glucose syrup, sorbitol powder, and croscarmellose sodium, along with about 83% of the batch quantity of milk powder, about 65% of the batch quantity of mannitol, and the sifted material of Step 2, were co-sifted using a No. 30 ASTM.

[0369] Step 4: The sifted ingredients of Step 3 were sifted a second time with a No. 30 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0370] Step 5: The batch quantity of crospovidone, along with the remaining batch quantities of mannitol and milk powder, and about 38% of the batch quantity of flavor agent (mixed berry), were co-sifted with a No. 30 ASTM.

[0371] Step 6: The sifted ingredients of Step 5 were sifted a second time with a No. 30 ASTM to form an extragranular ingredient mixture, which was collected in a polybag.

[0372] Step 7: The batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag.

[0373] Step 8: The batch quantity of maltitol solution was added to the batch quantity of glycerin under continuous stirring.

[0374] Step 9: The batch quantity of color agent was added to the mixture of Step 8 under continuous stirring. [0375] Step 10: The batch quantity of citric acid anhydrous, along with the remaining batch quantities of sucralose and flavor agent (mixed berry), were added to the mixture of Step 9 under continuous stirring.

[0376] Step 11: The mixture of Step 10 was stirred until a uniform dispersion was formed.

[0377] Step 12: The intragranular ingredient mixture of Step 4 was transferred to a rapid mixer granulator (with the impeller set to a slow speed and the chopper off) and mixed for approximately 10-minutes.

[0378] Step 13: The batch quantity of polyethylene glycol was slowly added to the mixture of Step 12 in a thin stream under continuous mixing (with the impeller set to a slow speed and the chopper on) with intermittent racking.

[0379] Step 14: The uniform dispersion of Step 11 was slowly added to the mixture of Step 13 in a thin stream (with the impeller set to a slow speed and the chopper on) with intermittent racking to form a wet mass.

[0380] Step 15: The extragranular ingredient mixture of Step 6 was slowly added to the wet mass of Step 14 under continuous mixing (with the impeller set to a slow speed and the chopper on), and the discharged material was collected on a tray.

[0381] Step 16: The material of Step 15 was passed through a cone mill to form milled wet granules. The cone mill was fitted with a 3mm screen, the knife was in the forward position, and the speed setting was slow.

[0382] Step 17: The wet granules of Step 16 were lubricated using the material of Step 7 for approximately 2-minutes.

[0383] Step 18: The wet granules from Step 17 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 13mm) PTFE punch tip to form a compressed tablet.

[0384] Step 19: The tablet from Step 18 was sprinkle coated using the batch quantity of fine sugar. [0385] Example 15: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 15 below. The ingredients corresponding to Example 15 are tabulated in Table 15 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 15, the active ingredients are phenylephrine HC1 and brompheniramine maleate. Each soft-chew tablet formed by the process of Example 15 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of brompheniramine maleate of about 4.0 mg. The amount of each ingredient provided in Table 15 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 15 can be used to make more soft- chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0386]

[0387] Procedure - Example 15

[0388] Step 1: The batch quantities of brompheniramine maleate, phenylephrine HC1 (coated), sodium bicarbonate, calcium gluconate, and bitter blocker, along with about 84% of the batch quantity of sucralose, were co-sifted using a No. 30 ASTM. [0389] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 30 ASTM and collected in a polybag.

[0390] Step 3: The batch quantities of dried glucose syrup, sorbitol powder, and croscarmellose sodium, along with about 83% of the batch quantity of milk powder, about 50% of the batch quantity of carnauba wax, about 62% of the batch quantity of mannitol, and the sifted material of Step 2, were co-sifted using a No. 30 ASTM.

[0391] Step 4: The sifted ingredients of Step 3 were sifted a second time with a No. 30 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0392] Step 5: The batch quantity of crospovidone, along with the remaining batch quantities of mannitol and milk powder, and about 38% of the batch quantity of flavor agent (mixed berry), were co-sifted with a No. 30 ASTM.

[0393] Step 6: The sifted ingredients of Step 5 were sifted a second time with a No. 30 ASTM to form an extragranular ingredient mixture, which was collected in a polybag.

[0394] Step 7: The remaining batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag.

[0395] Step 8: The batch quantity of sorbitol solution was added to the batch quantity of glycerin under continuous stirring.

[0396] Step 9: The batch quantity of color agent was added to the mixture of Step 8 under continuous stirring.

[0397] Step 10: The batch quantity of flavor agent (menthol freeze), along with the remaining batch quantities of sucralose and flavor agent (mixed berry), were added to the mixture of Step 9 under continuous stirring.

[0398] Step 11: The mixture of Step 10 was stirred until a uniform dispersion was formed.

[0399] Step 12: The intragranular ingredient mixture of Step 4 was transferred to a rapid mixer granulator (with the impeller set to a slow speed and the chopper off) and mixed for approximately 10-minutes.

[0400] Step 13: The batch quantity of polyethylene glycol was slowly added to the mixture of Step 12 in a thin stream under continuous mixing (with the impeller set to a slow speed and the chopper on) with intermittent racking. [0401 ] Step 14: The uniform dispersion of Step 11 was slowly added to the mixture of Step 13 in a thin stream (with the impeller set to a slow speed and the chopper on) with intermittent racking to form a wet mass.

[0402] Step 15: The extragranular ingredient mixture of Step 6 was slowly added to the wet mass of Step 14 under continuous mixing (with the impeller set to a slow speed and the chopper on), and the discharged material was collected on a tray.

[0403] Step 16: The material of Step 15 was passed through a cone mill to form milled wet granules. The cone mill was fitted with a 3mm screen, the knife was in the forward position, and the speed setting was slow.

[0404] Step 17: The wet granules of Step 16 were lubricated using the material of Step 7 for approximately 2-minutes.

[0405] Step 18: The wet granules from Step 17 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 18mm) PTFE punch tip to form a compressed tablet.

[0406] Step 19: The tablet from Step 18 was sprinkle coated using the batch quantity of fine sugar. [0407] Example 16: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 16 below. The ingredients corresponding to Example 16 are tabulated in Table 16 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 16, the active ingredients are phenylephrine HC1 and brompheniramine maleate. Each soft-chew tablet formed by the process of Example 16 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of brompheniramine maleate of about 4.0 mg. The amount of each ingredient provided in Table 16 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 16 can be used to make more soft- chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0408]

[0409] Procedure - Example 16

[0410] Step 1: The batch quantities of brompheniramine maleate and phenylephrine HC1, along with about 75% of the batch quantity of sucralose and about 67% of the batch quantity of sodium bicarbonate, were co-sifted using a No. 40 ASTM.

[0411] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 40 ASTM and collected in a polybag.

[0412] Step 3: The batch quantities of bitter blocker, maltodextrin, and croscarmellose sodium, along with about 61% of the batch quantity of mannitol, about 74% of the batch quantity of guar gum, and the sifted material of Step 2, were co-sifted using a No. 40 ASTM.

[0413] Step 4: The sifted ingredients of Step 3 were sifted a second time with a No. 40 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0414] Step 5: The batch quantities of monoammonium glycyrrhizinate and citric acid anhydrous, along with the remaining batch quantities of mannitol and guar gum, and about 33% of the batch quantity of flavor agent (mixed berry), were co-sifted with a No. 40 ASTM.

[0415] Step 6: The sifted ingredients of Step 5 were sifted a second time with a No. 40 ASTM to form an extragranular ingredient mixture, which was collected in a polybag.

[0416] Step 7: The batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag. [0417] Step 8: The batch quantity of sorbitol solution was added to the batch quantity of glycerin under continuous stirring.

[0418] Step 9: The batch quantity of color agent was added to the mixture of Step 8 under continuous stirring.

[0419] Step 10: The remaining batch quantities of flavor agent (mixed berry) and sucralose were added to the mixture of Step 9 under continuous stirring.

[0420] Step 11: The mixture of Step 10 was stirred until a uniform dispersion was formed.

[0421] Step 12: The intragranular ingredient mixture of Step 4 was mixed for approximately 2- minutes.

[0422] Step 13: The uniform dispersion of Step 11 was slowly added to the mixture of Step 12 in a thin stream to form a wet mass.

[0423] Step 14: The extragranular ingredient mixture of Step 6 was slowly added to the wet mass of Step 13 and then sifted using a No. 8 ASTM to form uniform wet granules.

[0424] Step 15: The wet granules of Step 14 were lubricated using the material of Step 7 for approximately 2-minutes.

[0425] Step 16: The wet granules from Step 15 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 18mm) PTFE punch tip, with one of the punch tips having the letter “P” embossed on one side, to form a compressed tablet.

[0426] Step 17: The tablet from Step 16 was sprinkle coated using the remaining batch quantity of sodium bicarbonate.

[0427] Example 17: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 17 below. The ingredients corresponding to Example 17 are tabulated in Table 17 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 17, the active ingredients are phenylephrine HC1 and brompheniramine maleate. Each soft-chew tablet formed by the process of Example 17 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of brompheniramine maleate of about 4.0 mg. The amount of each ingredient provided in Table 17 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 17 can be used to make more soft- chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0428]

[0429] Procedure - Example 17

[0430] Step 1: The batch quantities of maltodextrin, sorbitol powder, partially pregelatinized starch, croscarmellose sodium, and color agent, along with about 70% of the batch quantity of mannitol, were co-sifted using a No. 40 ASTM.

[0431] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 40 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0432] Step 3: The batch quantity of citric acid anhydrous, along with the remaining batch quantity of mannitol and about 33% of the batch quantity of flavor agent (mixed berry), were co-sifted with a No. 40 ASTM. [0433] Step 4: The sifted ingredients of Step 3 were sifted a second time with a No. 40 ASTM to form an cxtragranular ingredient mixture, which was collected in a polybag.

[0434] Step 5: The batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag.

[0435] Step 6: The batch quantity of propyl gallate was added to the batch quantity of propylene glycol under continuous stirring.

[0436] Step 7: The batch quantity of sorbitol solution was added to the batch quantity of glycerin under continuous stirring.

[0437] Step 8: The material of Step 6 was added to the material of Step 7 under continuous stirring. [0438] Step 9: The batch quantities of brompheniramine maleate and phenylephrine HC1 were added to the mixture of Step 8 under continuous stirring.

[0439] Step 10: The batch quantities of bitter blocker, neotame, sodium bicarbonate, and flavor agent (menthol freeze), along with the remaining batch quantity of flavor agent (mixed berry), were added to the mixture of Step 9 under continuous stirring.

[0440] Step 11: The mixture of Step 10 was stirred until a uniform dispersion was formed.

[0441] Step 12: The intragranular ingredient mixture of Step 2 was mixed for approximately 2- minutes.

[0442] Step 13: The uniform dispersion of Step 11 was slowly added to the mixture of Step 12 in a thin stream to form a wet mass.

[0443] Step 14: The extragranular ingredient mixture of Step 4 was slowly added to the wet mass of Step 13 and then sifted using a No. 8 ASTM to form uniform wet granules.

[0444] Step 15: The wet granules of Step 14 were lubricated using the material of Step 5 for approximately 2-minutes.

[0445] Step 16: The wet granules from Step 15 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 18mm) PTFE punch tip, with one of the punch tips having the letter “P” embossed on one side, to form a compressed tablet.

[0446] Step 17: The tablet from Step 16 was sprinkle coated using the batch quantity of fine sugar. [0447] Example 18: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 18 below. The ingredients corresponding to Example 18 are tabulated in Table 18 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. Tn Example 18, the active ingredients are diphenhydramine HC1 and acetaminophen. Each soft-chew tablet formed by the process of Example 18 has an active strength of acetaminophen of approximately 338 mg and an active strength of diphenhydramine HC1 of about 12.5 mg. The amount of each ingredient provided in Table 18 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 18 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0447]

[0449] Procedure - Example 18

[0450] Step 1: The batch quantity of dried glucose syrup, along with about 83% of the batch quantity of partially pregelatinized starch, about 78% of the batch quantity of milk powder, and about 82% of the batch quantity of mannitol, were co-sifted using a No. 30 ASTM.

[0451] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 30 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0452] Step 3: The remaining batch quantities of mannitol, milk powder, and partially pregelatinized starch, along with about 37% of the batch quantity of citric acid anhydrous and about 57% of the batch quantity of flavor agent (mixed berry), were co-sifted with a No. 30 ASTM. [0453] Step 4: The sifted ingredients of Step 3 were sifted a second time with a No. 30 ASTM to form an extragranular ingredient mixture, which was collected in a polybag.

[0454] Step 5: The batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag. [0455] Step 6: The batch quantity of maltitol solution was added to the batch quantity of glycerin under continuous stirring.

[0456] Step 7: The batch quantity of color agent was added to the mixture of Step 6 under continuous stirring.

[0457] Step 8: The remaining batch quantity of flavor agent (mixed berry), along with about 26% of the batch quantity of sucralose, were added to the mixture of Step 7 under continuous stirring. [0458] Step 9: The mixture of Step 8 was stirred until a uniform dispersion was formed.

[0459] Step 10: The intragranular ingredient mixture of Step 2 was transferred to a rapid mixer granulator (with the impeller set to a slow speed and the chopper off) and mixed for approximately 10-minutes.

[0460] Step 11: The batch quantity of com oil was slowly added to the mixture of Step 10 in a thin stream under continuous mixing (with the impeller set to a slow speed and the chopper on) with intermittent racking.

[0461] Step 12: The uniform dispersion of Step 9 was slowly added to the mixture of Step 11 in a thin stream (with the impeller set to a slow speed and the chopper on) with intermittent racking to form a wet mass.

[0462] Step 13: The extragranular ingredient mixture of Step 4 was slowly added to the wet mass of Step 12 under continuous mixing (with the impeller set to a slow speed and the chopper on), and the discharged material was collected on a tray.

[0463] Step 14: The material of Step 13 was passed through a cone mill to form milled granules. The cone mill was fitted with a 4mm screen, the knife was in the forward position, and the speed setting was slow.

[0464] Step 15: The granules of Step 14 were lubricated using the material of Step 5 for approximately 2-minutes.

[0465] Step 16: The batch quantity of magnesium stearate was sifted using a No. 60 ASTM and mixed with the pre-lubricated material of Step 15 for approximately 2-minutes in a multi-blender. [0466] Step 17: The batch quantities of acetaminophen (coated) and diphenhydramine HC1 (coated), along with the remaining batch quantities of sucralose and citric acid anhydrous, and the lubricated wet granules of Step 16, were sifted using a No. 8 ASTM.

[0467] Step 18: The wet granules from Step 17 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 22mm) PTFE punch tip, with one of the punch tips having the letters “CT” embossed on one side, to form a compressed tablet.

[0468] Example 19: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 19 below. The ingredients corresponding to Example 19 are tabulated in Table 19 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 19, the active ingredients are dextromethorphan HBr and acetaminophen. Each soft-chew tablet formed by the process of Example 19 has an active strength of acetaminophen of approximately 338 mg and an active strength of dextromethorphan HBr of about 7.3 mg. The amount of each ingredient provided in Table 19 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 19 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0469]

[0470] Procedure - Example 19

[0471] Step 1: The batch quantity of dried glucose syrup, along with about 83% of the batch quantity of partially pregelatinized starch, about 78% of the batch quantity of milk powder, and about 82% of the batch quantity of mannitol, were co-sifted using a No. 30 ASTM.

[0472] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 30 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0473] Step 3: The remaining batch quantities of mannitol, milk powder, and partially pregelatinized starch, along with about 37% of the batch quantity of citric acid anhydrous and about 57 % of the batch quantity of flavor agent (mixed berry), were co-sifted with a No. 30 ASTM. [0474] Step 4: The sifted ingredients of Step 3 were sifted a second time with a No. 30 ASTM to form an extragranular ingredient mixture, which was collected in a polybag. [0475] Step 5: The batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag.

[0476] Step 6: The batch quantity of maltitol solution was added to the batch quantity of glycerin under continuous stirring.

[0477] Step 7: The batch quantity of color agent was added to the mixture of Step 6 under continuous stirring.

[0478] Step 8: The remaining batch quantity of flavor agent (mixed berry), along with about 31% of the batch quantity of sucralose, were added to the mixture of Step 7 under continuous stirring. [0479] Step 9: The mixture of Step 8 was stirred until a uniform dispersion was formed.

[0480] Step 10: The intragranular ingredient mixture of Step 2 was transferred to a rapid mixer granulator (with the impeller set to a slow speed and the chopper off) and mixed for approximately 10-minutes.

[0481] Step 11: The batch quantity of com oil was slowly added to the mixture of Step 10 in a thin stream under continuous mixing (with the impeller set to a slow speed and the chopper on) with intermittent racking.

[0482] Step 12: The uniform dispersion of Step 9 was slowly added to the mixture of Step 11 in a thin stream (with the impeller set to a slow speed and the chopper on) with intermittent racking to form a wet mass.

[0483] Step 13: The extragranular ingredient mixture of Step 4 was slowly added to the wet mass of Step 12 under continuous mixing (with the impeller set to a slow speed and the chopper on), and the discharged material was collected on a tray.

[0484] Step 14: The material of Step 13 was passed through a cone mill to form milled granules. The cone mill was fitted with a 4mm screen, the knife was in the forward position, and the speed setting was slow.

[0485] Step 15: The granules of Step 14 were pre-lubricated using the material of Step 5 for approximately 2-minutes in a multi-blender.

[0486] Step 16: The batch quantity of magnesium stearate was sifted using a No. 60 ASTM and mixed with the pre-lubricated material of Step 15 for approximately 2-minutes in a multi-blender. [0487] Step 17: The batch quantity of dextromethorphan HBr base was added to the acetone under continuous stirring. [0488] Step 18: The batch quantities of amino methacrylate copolymer and calcium gluconate, along with the remaining batch quantity of sucralose, were added to the mixture of Step 17 under continuous stirring.

[0489] Step 19: The batch quantity of magnesium oxide was added to the uniform dispersion of Step 18 and allowed to dry.

[0490] Step 20: The dried material of Step 19 was sifted using a No. 40 ASTM and collected in a polybag.

[0491] Step 21: The batch quantity of acetaminophen (coated), along with the remaining batch quantity of citric acid anhydrous, the material of Step 20, and the granules of Step 16, were mixed in a polybag and co-sifted using a No. 8 ASTM.

[0492] Step 22: The wet granules from Step 21 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 22mm) PTFE punch tip, with one of the punch tips having the letters “CI” embossed on one side, to form a compressed tablet.

[0493] Example 20: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 20 below. The ingredients corresponding to Example 20 are tabulated in Table 20 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 20, the active ingredients are dextromethorphan HBr and acetaminophen. Each soft-chew tablet formed by the process of Example 20 has an active strength of acetaminophen of approximately 325 mg and an active strength of dextromethorphan HBr of about 7.3 mg. The amount of each ingredient provided in Table 20 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 20 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0494]

[0495] Procedure - Example 20

[0496] Step 1: The batch quantities of carboxymethylcellulose calcium, sucralose, calcium gluconate, bitter blocker powder, milk powder, dried glucose syrup, sorbitol powder, flavor agent (apple cinnamon), croscarmellose sodium, color agent, and mannitol, along with about 54% of the batch quantity of carnauba wax, were co-sifted using a No. 40 ASTM.

[0497] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 40 ASTM and collected in a container.

[0498] Step 3: The batch quantities of acetaminophen and polyethylene glycol were co-sifted using a No. 40 ASTM.

[0499] Step 4: The sifted ingredients of Step 2 and Step 3 were co-sifted using a No. 40 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0500] Step 5: The batch quantity of crospovidone was sifted with a No. 40 ASTM and collected in a polybag.

[0501] Step 6: The remaining batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag. [0502] Step 7: The batch quantities of dextromethorphan HBr, amino methacrylate copolymer, and ncotamc were added to the batch quantity of glycerin under continuous stirring.

[0503] Step 8: The batch quantity of non-crystallizing sorbitol solution was added to the mixture of Step 7 under continuous stirring.

[0504] Step 9: The mixture of Step 8 was stirred until a uniform dispersion was formed.

[0505] Step 10: The intragranular ingredient mixture of Step 4 was transferred to a rapid mixer granulator (with the impeller set to a slow speed and the chopper off) and mixed for approximately 10-minutes.

[0506] Step 11: The uniform dispersion of Step 9 was slowly added to the mixture of Step 10 in a thin stream (with the impeller set to a slow speed and the chopper on) with intermittent racking to form a wet mass.

[0507] Step 12: The sifted material of Step 5 was slowly added to the wet mass of Step 11 under continuous mixing (with the impeller set to a slow speed and the chopper on), and the discharged material was collected on a tray.

[0508] Step 13: The material of Step 12 was passed through a cone mill to form milled wet granules. The cone mill was fitted with a 3mm screen, the knife was in the forward position, and the speed setting was slow.

[0509] Step 14: The wet granules of Step 13 were lubricated using the material of Step 6 for approximately 2-minutes.

[0510] Step 15: The wet granules from Step 14 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) PTFE punch tip, with one of the punch tips having the letter “R” embossed on one side, to form a compressed tablet.

[0511] Step 16: The tablet from Step 15 was coated using the batch quantity of sucrose.

[0512] Example 21: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 21 below. The ingredients corresponding to Example 21 are tabulated in Table 21 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 21, the active ingredients are dextromethorphan HBr and acetaminophen. Each soft-chew tablet formed by the process of Example 21 has an active strength of acetaminophen of approximately 325 mg and an active strength of dextromethorphan HBr of about 7.3 mg. The amount of each ingredient provided in Table 21 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 21 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0513]

[0514] Procedure - Example 21

[0515] Step 1: The batch quantities of carboxymethylcellulose calcium, citric acid anhydrous, color agent, dried glucose syrup, flavor agent (apple), flavor agent (cinnamon), mannitol, milk powder, and sorbitol powder, along with about 42% of the batch quantity of carnauba wax, about 46% of the batch quantity of silicified microcrystalline cellulose, and about 34% of the batch quantity of crospovidone, were co-sifted using a No. 40 ASTM. [0516] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 40 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0517] Step 3: The batch quantities of acetaminophen and malic acid, along with about 36% of the batch quantity of sucralose, about 23% of the batch quantity of bitter blocker, and about 40% of the batch quantity of monoammonium glycyrrhizinate, were co-sifted using a No. 40 ASTM.

[0518] Step 4: The sifted ingredients of Step 3 were sifted a second time with a No. 40 ASTM and collected in a polybag.

[0519] Step 5: The remaining batch quantity of crospovidone, along with the remaining batch quantity of silicified microcrystalline cellulose, were co-sifted with a No. 40 ASTM.

[0520] Step 6: The sifted ingredients of Step 5 were sifted a second time with a No. 40 ASTM to form an extragranular ingredient mixture, which was collected in a polybag.

[0521] Step 7: The batch quantities of dextromethorphan HBr, pea maltodextrin, calcium gluconate, and sodium gluconate, along with the remaining batch quantities of monoammonium glycyrrhizinate, and bitter blocker, and about 51% of the batch quantity of sucralose, were cosifted using a No. 60 ASTM.

[0522] Step 8: The sifted ingredients of Step 7 were sifted a second time with a No. 60 ASTM and collected in a polybag.

[0523] Step 9: The remaining batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag.

[0524] Step 10: The remaining batch quantity of sucralose was added to the batch quantity of glycerin under continuous stirring.

[0525] Step 11: The batch quantity of non-crystallizing sorbitol solution was added to the mixture of Step 10 under continuous stirring.

[0526] Step 12: The mixture of Step 11 was stirred until a uniform dispersion was formed.

[0527] Step 13: The intragranular ingredient mixture of Step 2 was mixed for approximately 10- minutes.

[0528] Step 14: The uniform dispersion of Step 12 was slowly added to the mixture of Step 13 in a thin stream to form a wet mass.

[0529] Step 15: The mixture of Step 4 was added to the wet mass of Step 14 under continuous mixing. [0530] Step 16: The extragranular ingredient mixture of Step 6 was slowly added to the wet mass of Step 15 under continuous mixing.

[0531] Step 17 : The material of Step 16 was sifted using a No. 8 ASTM and collected in a polybag. [0532] Step 18: The mixture of Step 8 was added to the wet mass of Step 18 under continuous mixing.

[0533] Step 19: The wet granules of Step 18 were lubricated using the material of Step 9 for approximately 2-minutes.

[0534] Step 20: The wet granules from Step 19 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) PTFE punch tip (length not less than 2.00 mm), with one of the punch tips having the letter “R” embossed on one side, to form a compressed tablet.

[0535] Step 21: The tablet from Step 20 was coated using the batch quantity of sucrose.

[0536] Example 22: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 22 below. The ingredients corresponding to Example 22 are tabulated in Table 22 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 22, the active ingredients are diphenhydramine HC1 and acetaminophen. Each soft-chew tablet formed by the process of Example 22 has an active strength of acetaminophen of approximately 325 mg and an active strength of diphenhydramine HC1 of about 12.5 mg. The amount of each ingredient provided in Table 22 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 22 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0537]

[0538] Procedure - Example 22

[0539] Step 1: The batch quantities of bitter blocker, calcium gluconate, carboxymethylcellulose calcium, color agent, croscarmellose sodium, dried glucose syrup, mannitol, milk powder, and sorbitol powder, along with about 60% of the batch quantity of sucralose, about 22% of the batch quantity of flavor agent (apple cinnamon), and about 54% of the batch quantity of carnauba wax, were co-sifted using a No. 40 ASTM.

[0540] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 40 ASTM.

[0541] Step 3: The batch quantities of acetaminophen and polyethylene glycol were co-sifted using a No. 40 ASTM. [0542] Step 4: The sifted ingredients of Step 2 and Step 3 were co-sifted using a No. 40 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0543] Step 5: The batch quantity of crospovidone, along with the remaining batch quantities of sucralose and flavor agent (apple cinnamon), were co-sifted with a No. 40 ASTM to form an extragranular ingredient mixture, which was collected in a polybag.

[0544] Step 6: The remaining batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag.

[0545] Step 7: The batch quantities of diphenhydramine HC1, amino methacrylate copolymer, and neotame were added to the batch quantity of glycerin under continuous stirring.

[0546] Step 8: The batch quantity of non-crystallizing sorbitol solution was added to the mixture of Step 7 under continuous stirring.

[0547] Step 9: The mixture of Step 8 was stirred until a uniform dispersion was formed.

[0548] Step 10: The intragranular ingredient mixture of Step 4 was transferred to a rapid mixer granulator (with the impeller set to a slow speed and the chopper off) and mixed for approximately 10-minutes.

[0549] Step 11: The uniform dispersion of Step 9 was slowly added to the mixture of Step 10 in a thin stream (with the impeller set to a slow speed and the chopper on) with intermittent racking to form a wet mass.

[0550] Step 12: The extragranular ingredient mixture of Step 5 was slowly added to the wet mass of Step 11 under continuous mixing.

[0551] Step 13: The material of Step 12 was passed through a cone mill to form milled wet granules. The cone mill was fitted with a 3mm screen, the knife was in the forward position, and the speed setting was slow.

[0552] Step 14: The wet granules of Step 13 were lubricated using the material of Step 6 for approximately 2-minutes.

[0553] Step 15: The wet granules from Step 14 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) PTFE punch tip, with one of the punch tips having the letter “R” embossed on one side, with a compression force of 0.5 kN to form a compressed tablet.

[0554] Step 16: The tablet from Step 15 was coated using the batch quantity of sucrose. [0555] Example 23: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 23 below. The ingredients corresponding to Example 23 are tabulated in Table 23 with the amount of each ingredient used in the process given in percent -by-weight and in milligrams. In Example 23, the active ingredient is diphenhydramine gluconate and acetaminophen. Each soft-chew tablet formed by the process of Example 23 has an active strength of acetaminophen of approximately 325 mg and an active strength of diphenhydramine HC1 of about 12.5 mg. The amount of each ingredient provided in Table 23 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 23 can be used to make more soft- chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0556]

[0557] Procedure - Example 23

[0558] Step 1 : The batch quantities of dried glucose syrup, flavor agent (cinnamon), flavor agent (apple), milk powder, mannitol, color agent, and citric acid anhydrous were co-sifted using a No. 40 ASTM.

[0559] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 40 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0560] Step 3: The batch quantity of partially pregelatinized starch was sifted with a No. 40 ASTM and collected in a polybag.

[0561] Step 4: The batch quantities of acetaminophen, diphenhydramine HC1, sodium gluconate, malic acid, and monoammonium glycyrrhizinate, along with about 86% of the batch quantity of sucralose, were co-sifted using a No. 40 ASTM. [0562] Step 5: The sifted ingredients of Step 4 were sifted a second time with a No. 40 ASTM and collected in a polybag.

[0563] Step 6: The batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag.

[0564] Step 7: The remaining batch quantity of sucralose was added to the batch quantity of glycerin under continuous stirring.

[0565] Step 8: The batch quantity of maltitol solution was added to the mixture of Step 7 under continuous stirring.

[0566] Step 9: The mixture of Step 8 was stirred until a uniform dispersion was formed.

[0567] Step 10: The intragranular ingredient mixture of Step 2 was mixed for approximately 5- minutes.

[0568] Step 11: The uniform dispersion of Step 9 was slowly added to the mixture of Step 10 in a thin stream to form a wet mass.

[0569] Step 12: The sifted material of Step 3 was slowly added to the wet mass of Step 11 under continuous mixing and then sifted using a No. 8 ASTM to form uniform wet granules.

[0570] Step 13: The wet granules of Step 12 were lubricated using the material of Step 6 for approximately 2-minutes.

[0571] Step 14: The material of Step 5 was added to the material of Step 13 under continuous mixing.

[0572] Step 15: The wet granules from Step 14 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) PTFE punch tip, with one of the punch tips having the letter “T” embossed on one side, to form a compressed tablet.

[0573] Step 16: The tablet from Step 15 was coated using the batch quantity of sucrose.

[0574] Example 24: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 24 below. The ingredients corresponding to Example 24 are tabulated in Table 24 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 24, the active ingredient is dextromethorphan HBr and doxylamine succinate. Each soft-chew tablet formed by the process of Example 24 has an active strength of dextromethorphan HBr of approximately 11 mg and an active strength of doxylamine succinate of about 6.25 mg. The amount of each ingredient provided in Table 24 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 24 can be used to make more soft- chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0575]

[0576] Procedure - Example 24

[0577] Step 1: The batch quantities of sucralose, carboxymethylcellulose calcium, bitter blocker powder, milk powder, calcium gluconate, dried glucose syrup, mannitol, sorbitol powder, and croscarmellose sodium, along with about 50% of the batch quantity of citric acid anhydrous, about 50% of the batch quantity of flavor agent (menthol freeze), and about 54% of the batch quantity of carnauba wax, were co-sifted using a No. 40 ASTM. [0578] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 40 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0579] Step 3: The batch quantity of crospovidone, along with the remaining batch quantities of citric acid anhydrous and flavor agent (menthol freeze), and about 66% of the batch quantity of flavor agent (mixed berry), were co-sifted with a No. 40 ASTM.

[0580] Step 4: The sifted ingredients of Step 3 were sifted a second time with a No. 40 ASTM to form an extragranular ingredient mixture, which was collected in a polybag.

[0581] Step 5: The remaining batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag.

[0582] Step 6: The batch quantities of dextromethorphan HBr and doxylamine succinate were added to the batch quantity of glycerin under continuous stirring.

[0583] Step 7: The batch quantities of neotame and amino methacrylate copolymer were added to the mixture of Step 6 under continuous stirring.

[0584] Step 8: The batch quantities of color agent (FD&C blue) and color agent (FD&C red), along with the remaining batch quantity of flavor agent (mixed berry), were added to the mixture of Step 7 under continuous stirring.

[0585] Step 9: The batch quantity of non-crystallizing sorbitol solution was added to the mixture of Step 8 under continuous stirring.

[0586] Step 10: The mixture of Step 9 was stirred until a uniform dispersion was formed.

[0587] Step 11: The intragranular ingredient mixture of Step 2 was transferred to a rapid mixer granulator (with the impeller set to a slow speed and the chopper off) and mixed for approximately 10-minutes.

[0588] Step 12: The batch quantity of polyethylene glycol 600 was slowly added to the mixture of Step 11 in a thin stream under continuous mixing (with the impeller set to a slow speed and the chopper on) with intermittent racking.

[0589] Step 13: The uniform dispersion of Step 10 was slowly added to the mixture of Step 12 in a thin stream (with the impeller set to a slow speed and the chopper on) with intermittent racking to form a wet mass.

[0590] Step 14: The extragranular ingredient mixture of Step 3 was slowly added to the wet mass of Step 13 under continuous mixing. [0591 ] Step 15: The material of Step 14 was passed through a cone mill to form milled wet granules. The cone mill was fitted with a 3mm screen, the knife was in the forward position, and the speed setting was slow.

[0592] Step 16: The wet granules of Step 15 were lubricated using the material of Step 5 for approximately 2-minutes.

[0593] Step 17: The wet granules from Step 16 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) PTFE punch tip, with one of the punch tips having the letter “R” embossed on one side, to form a compressed tablet.

[0594] Step 18: The tablet from Step 17 was coated using the batch quantity of sucrose.

[0595] Example 25: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 25 below. The ingredients corresponding to Example 25 are tabulated in Table 25 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 25, the active ingredients are dextromethorphan HBr and doxylamine succinate. Each soft-chew tablet formed by the process of Example 25 has an active strength of dextromethorphan HBr of approximately 11 mg and an active strength of doxylamine succinate of about 6.25 mg. The amount of each ingredient provided in Table 25 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 25 can be used to make more soft- chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0596]

[0597] Procedure - Example 25

[0598] Step 1: The batch quantities of carboxy methylcellulose calcium, color agent (FD&C blue), color agent (FD&C red), dried glucose syrup, flavor agent (menthol freeze), mannitol, milk powder, and sorbitol powder, along with about 45% of the batch quantity of carnauba wax, about 34% of the batch quantity of crospovidone, about 51% of the batch quantity of flavor agent (honey), about 29% of the batch quantity of flavor agent (mixed berry), and about 46% of the batch quantity of silicified microcrystalline cellulose, were co-sifted using a No. 40 ASTM. [0599] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 40 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0600] Step 3: The remaining batch quantities of crospovidone and silicified microcrystalline cellulose were co-sifted with a No. 40 ASTM to form an extragranular ingredient mixture, which was collected in a polybag.

[0601] Step 4: The batch quantities of calcium gluconate, dextromethorphan HBr, maltodextrin, monoammonium glycyrrhizinate, and sodium gluconate, along with about 75% of the batch quantity of bitter blocker and about 40% of the batch quantity of sucralose, were co-sifted using a No. 60 ASTM.

[0602] Step 5: The sifted ingredients of Step 4 were sifted a second time with a No. 60 ASTM and collected in a polybag.

[0603] Step 6: The batch quantity of doxylamine succinate, along with about 40% of the batch quantity of sucralose and the remaining batch quantity of bitter blocker, were co-sifted using a No. 40 ASTM and collected in a polybag.

[0604] Step 7: The remaining batch quantity of sucralose was added to the batch quantity of glycerin under continuous stirring.

[0605] Step 8: The batch quantity of non-crystallizing sorbitol solution, along with the remaining batch quantities of flavor agent (honey) and flavor agent (mixed berry), were added to the mixture of Step 7 under continuous stirring.

[0606] Step 9: The mixture of Step 8 was stirred until a uniform dispersion was formed.

[0607] Step 10: The intragranular ingredient mixture of Step 2 was mixed for approximately 5- minutes.

[0608] Step 11: The uniform dispersion of Step 9 was slowly added to the mixture of Step 10 in a thin stream to form a wet mass.

[0609] Step 12: The extragranular ingredient mixture of Step 3 was slowly added to the wet mass of Step 11 under continuous mixing and then sifted using a No. 8 ASTM to form uniform granules. [0610] Step 13: The mixture of Step 5 was added to the wet mass of Step 12 under continuous mixing.

[0611] Step 14: The mixture of Step 6 was added to the material of Step 13 under continuous mixing. [0612] Step 15 : The wet granules of Step 14 were lubricated using the remaining batch quantity of carnauba wax for approximately 2-minutcs.

[0613] Step 16: The wet granules from Step 15 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) PTFE punch tip, with one of the punch tips having the letter “R” embossed on one side, to form a compressed tablet.

[0614] Step 17: The tablet from Step 16 was coated using the batch quantity of sucrose.

[0615] Example 26: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 26 below. The ingredients corresponding to Example 26 are tabulated in Table 26 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 26, the active ingredients are guaifenesin and dextromethorphan HBr. Each soft-chew tablet formed by the process of Example 26 has an active strength of guaifenesin of approximately 100 mg and an active strength of dextromethorphan HBr of about 3.65 mg. The amount of each ingredient provided in Table 26 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 26 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0616]

[0617] Procedure - Example 26 [0618] Step 1 : The batch quantities of bitter blocker, croscarmellose sodium, flavor agent (orange), guaifenesin, and sodium bicarbonate, along with about 60% of the batch quantity of amino methacrylate copolymer, about 60% of the batch quantity of carnauba wax, about 74% of the batch quantity of dried glucose syrup, about 75% of the batch quantity of milk powder, about 37% of the batch quantity of monoammonium glycyrrhizinate (solid), about 67% of the batch quantity of partially pregelatinized starch, about 51% of the batch quantity of silicified microcrystalline cellulose, and about 29% of the batch quantity of sucralose, were co-sifted using a No. 40 ASTM. [0619] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 40 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0620] Step 3: The batch quantity of sodium gluconate, along with about 70% of the batch quantity of flavor agent (menthol freeze), about 37% of the batch quantity of monoammonium glycyrrhizinate (solid), about 29% of the batch quantity of sucralose, and the remaining batch quantities of silicified microcrystalline cellulose, milk powder, partially pregelatinized starch, and dried glucose syrup, were co-sifted with a No. 40 ASTM to form an extragranular ingredient mixture, which was collected in a polybag.

[0621] Step 4: The batch quantities of dextromethorphan HBr, maltodextrin, and calcium gluconate, along with about 29% of the batch quantity of sucralose and the remaining batch quantity of monoammonium glycyrrhizinate (solid), were co-sifted using a No. 60 ASTM.

[0622] Step 5: The sifted ingredients of Step 4 were sifted a second time with a No. 60 ASTM and collected in a polybag.

[0623] Step 6: The remaining batch quantity of sucralose was added to the batch quantity of glycerin under continuous stirring.

[0624] Step 7: The remaining batch quantity of amino methacrylate copolymer was added to the mixture of Step 6 under continuous stirring.

[0625] Step 8: The mixture of Step 7 was stirred until a uniform dispersion was formed.

[0626] Step 9: The batch quantity of ethanol was added to the mixture of Step 8 under continuous stirring.

[0627] Step 10: The batch quantity of carboxymethylcellulose calcium was added to the mixture of Step 9 under continuous stirring. [0628] Step 11 : The batch quantities of zinc gluconate, neotame, sodium chloride, bitter blocker (solid), monoammonium glycyrrhizinatc (liquid), and flavor agent (peppermint) were added to the mixture of Step 10 under continuous stirring.

[0629] Step 12: The batch quantity of polyvinylpyrrolidone K30 was added to the mixture of Step 11 under continuous stirring.

[0630] Step 13: The batch quantity of bitter blocker (liquid) and the remaining batch quantity of flavor agent (menthol freeze) were added to the mixture of Step 12 under continuous stirring.

[0631] Step 14: The batch quantity of color agent (FD&C yellow) was added to the mixture of Step 13 under continuous stirring.

[0632] Step 15: The mixture of Step 14 was stirred until a uniform dispersion was formed.

[0633] Step 16: The intragranular ingredient mixture of Step 2 was mixed for approximately 10- minutes.

[0634] Step 17: The uniform dispersion of Step 15 was slowly added to the mixture of Step 16 in a thin stream with intermittent racking to form a wet mass.

[0635] Step 18: The extragranular ingredient mixture of Step 3 was added to the wet mass of Step 17 under continuous mixing.

[0636] Step 19: The mixture of Step 4 was added to the material of Step 18 under continuous mixing.

[0637] Step 20: The wet granules of Step 19 were lubricated using the remaining batch quantity of carnauba wax for approximately 2-minutes.

[0638] Step 21: The wet granules from Step 20 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) PTFE punch tip, with one of the punch tips having the letter “R” embossed on one side, to form a compressed tablet.

[0639] Step 22: The tablet from Step 21 was coated using the batch quantity of sucrose.

[0640] Example 27: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 27 below. The ingredients corresponding to Example 27 are tabulated in Table 27 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 27, the active ingredients are phenylephrine HC1 and doxylamine succinate. Each soft-chew tablet formed by the process of Example 27 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of doxylamine succinate of about 12.50 mg. The amount of each ingredient provided in Table 27 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 27 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0641 ]

[0642] Procedure - Example 27

[0643] Step 1: The batch quantities of phenylephrine HC1 (coated), sucralose, sodium chloride, sodium gluconate, carboxymethylcellulose calcium, sorbitol powder, croscarmellose sodium, partially pregelatinized starch, and mannitol were co-sifted using a No. 30 ASTM.

[0644] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 30 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0645] Step 3: The batch quantities of hydrogenated vegetable oil and flavor agent (honey) were co-sifted with a No. 30 ASTM. [0646] Step 4: The sifted ingredients of Step 3 were sifted a second time with a No. 30 ASTM and collected in a polybag.

[0647] Step 5: The batch quantity of doxylamine succinate was added to the batch quantity of simethicone under continuous stirring.

[0648] Step 6: The batch quantity of color agent was added to the batch quantity of maltitol solution under continuous stirring.

[0649] Step 7: The batch quantities of neotame, flavor agent (menthol freeze), bitter blocker, BHA, BHT, and edetate disodium were added to the mixture of Step 6 under continuous stirring.

[0650] Step 8: The mixture of Step 7 was stirred until a uniform dispersion was formed.

[0651] Step 9: The intragranular ingredient mixture of Step 2 was mixed for approximately 2- minutes.

[0652] Step 10: The material of Step 5 was added to the mixture of Step 9 in a thin stream under continuous mixing.

[0653] Step 11: The uniform dispersion of Step 8 was slowly added to the mixture of Step 10 in a thin stream under continuous mixing to form a wet mass.

[0654] Step 12: The wet mass of Step 11 was sifted using a No. 8 ASTM to form wet granules that were collected in a tray.

[0655] Step 13: The wet granules of Step 12 were lubricated using the material of Step 4 for approximately 2-minutes.

[0656] Step 14: The wet granules from Step 13 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) PTFE punch tip, with one of the punch tips having the letter “T” embossed on one side, to form a compressed tablet.

[0657] Step 15: The tablet from Step 14 was coated using the batch quantity of fine sugar.

[0658] Example 28: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 28 below. The ingredients corresponding to Example 28 are tabulated in Table 28 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 28, the active ingredients are phenylephrine HC1 and doxylamine succinate. Each soft-chew tablet formed by the process of Example 28 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of doxylamine succinate of about 12.50 mg. The amount of each ingredient provided in Table 28 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 28 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0659]

[0660] Procedure - Example 28

[0661] Step 1: The batch quantities of phenylephrine HC1, sucralose, sodium chloride, sodium gluconate, carboxymethylcellulose calcium, sorbitol powder, croscarmellose sodium, partially pregelatinized starch, and mannitol were co-sifted using a No. 30 ASTM.

[0662] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 30 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0663] Step 3: The batch quantities of hydrogenated vegetable oil and flavor agent (honey) were co-sifted with a No. 30 ASTM. [0664] Step 4: The sifted ingredients of Step 3 were sifted a second time with a No. 30 ASTM and collected in a polybag.

[0665] Step 5: The batch quantity of doxylamine succinate was added to the batch quantity of simethicone under continuous stirring.

[0666] Step 6: The batch quantity of color agent was added to the batch quantity of maltitol solution under continuous stirring.

[0667] Step 7: The batch quantities of neotame, flavor agent (menthol freeze), bitter blocker, BHA, BHT, and edetate disodium were added to the mixture of Step 6 under continuous stirring.

[0668] Step 8: The mixture of Step 7 was stirred until a uniform dispersion was formed.

[0669] Step 9: The intragranular ingredient mixture of Step 2 was mixed for approximately 2- minutes.

[0670] Step 10: The material of Step 5 was added to the mixture of Step 9 in a thin stream under continuous mixing.

[0671] Step 11: The uniform dispersion of Step 8 was slowly added to the mixture of Step 10 in a thin stream under continuous mixing to form a wet mass.

[0672] Step 12: The wet mass of Step 11 was sifted using a No. 8 ASTM to form wet granules that were collected in a tray.

[0673] Step 13: The wet granules of Step 12 were lubricated using the material of Step 4 for approximately 2-minutes.

[0674] Step 14: The wet granules from Step 13 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) PTFE punch tip, with one of the punch tips having the letter “T” embossed on one side, to form a compressed tablet.

[0675] Step 15: The tablet from Step 14 was coated using the batch quantity of fine sugar.

[0676] Example 29: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 29 below. The ingredients corresponding to Example 29 are tabulated in Table 29 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 29, the active ingredients are phenylephrine HC1 and brompheniramine maleate. Each soft-chew tablet formed by the process of Example 29 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of brompheniramine maleate of about 4.00 mg. The amount of each ingredient provided in Table 29 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 29 can be used to make more soft- chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0677]

[0678] Procedure - Example 29

[0679] Step 1 : The batch quantities of brompheniramine maleate, sucralose, phenylephrine HC1 (coated), sodium gluconate, color agent (FD&C red), sorbitol powder, croscarmellose sodium, and mannitol were co-sifted using a No. 40 ASTM.

[0680] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 40 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0681] Step 3: The batch quantity of hydrogenated vegetable oil was sifted with a No. 40 ASTM.

[0682] Step 4: The sifted material of Step 3 was sifted a second time with a No. 40 ASTM and collected in a polybag.

[0683] Step 5: The batch quantity of neotame was added to the batch quantity of maltitol solution under continuous stirring. [0684] Step 6: The batch quantities of flavor agent (menthol freeze), BHA, BHT, edetate disodium, and flavor agent (mixed berry) were added to the mixture of Step 5 under continuous stirring.

[0685] Step 7: The mixture of Step 6 was stirred until a uniform dispersion was formed.

[0686] Step 8: The intragranular ingredient mixture of Step 2 was mixed for approximately 2- minutes.

[0687] Step 9: The batch quantity of simethicone was slowly added to the mixture of Step 8 in a thin stream under continuous mixing.

[0688] Step 10: The uniform dispersion of Step 7 was slowly added to the mixture of Step 9 in a thin stream under continuous mixing to form a wet mass.

[0689] Step 11: The wet mass of Step 10 was sifted using a No. 8 ASTM to form wet granules that were collected in a tray.

[0690] Step 12: The wet granules of Step 11 were lubricated using the material of Step 4 for approximately 2-minutes.

[0691] Step 13: The wet granules from Step 12 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) PTFE punch tip, with one of the punch tips having the letter “P” embossed on one side, with a compression force of 2 kN to form a compressed tablet.

[0692] Step 14: The tablet from Step 13 was sprinkled using the batch quantity of fine sugar.

[0693] Example 30: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 30 below. The ingredients corresponding to Example 30 are tabulated in Table 30 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 30, the active ingredients are phenylephrine HC1 and brompheniramine maleate. Each soft-chew tablet formed by the process of Example 30 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of brompheniramine maleate of about 4.00 mg. The amount of each ingredient provided in Table 30 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 30 can be used to make more soft- chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0695] Procedure - Example 30

[0696] Step 1: The batch quantities of brompheniramine maleate, sucralose, phenylephrine HC1, sodium gluconate, color agent (FD&C red), sorbitol powder, croscarmellose sodium, and mannitol were co-sifted using a No. 40 ASTM.

[0697] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 40 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0698] Step 3: The batch quantity of hydrogenated vegetable oil was sifted with a No. 40 ASTM.

[0699] Step 4: The sifted material of Step 3 was sifted a second time with a No. 40 ASTM and collected in a polybag.

[0700] Step 5: The batch quantity of neotame was added to the batch quantity of maltitol solution under continuous stirring.

[0701] Step 6: The batch quantities of flavor agent (menthol freeze), BHA, BHT, edetate disodium, and flavor agent (mixed berry) were added to the mixture of Step 5 under continuous stirring.

[0702] Step 7: The mixture of Step 6 was stirred until a uniform dispersion was formed. [0703] Step 8: The intragranular ingredient mixture of Step 2 was mixed for approximately 2- minutcs.

[0704] Step 9: The batch quantity of simethicone was slowly added to the mixture of Step 8 in a thin stream under continuous mixing.

[0705] Step 10: The uniform dispersion of Step 7 was slowly added to the mixture of Step 9 in a thin stream under continuous mixing to form a wet mass.

[0706] Step 11: The wet mass of Step 10 was sifted using a No. 8 ASTM to form wet granules that were collected in a tray.

[0707] Step 12: The wet granules of Step 11 were lubricated using the material of Step 4 for approximately 2-minutes.

[0708] Step 13: The wet granules from Step 12 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) PTFE punch tip, with one of the punch tips having the letter “P” embossed on one side, to form a compressed tablet.

[0709] Step 14: The tablet from Step 13 was sprinkled using the batch quantity of fine sugar.

[0710] Example 31: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 31 below. The ingredients corresponding to Example 31 are tabulated in Table 31 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 31, the active ingredients are phenylephrine HC1 and brompheniramine maleate. Each soft-chew tablet formed by the process of Example 31 has an active strength of phenylephrine HC1 of approximately 10 mg and an active strength of brompheniramine maleate of about 4.00 mg. The amount of each ingredient provided in Table 31 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 31 can be used to make more soft- chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0711]

[0712] Procedure - Example 31

[0713] Step 1: The batch quantities of brompheniramine maleate, phenylephrine HC1 (coated), sodium gluconate, color agent (FD&C red), sorbitol powder, croscarmellose sodium, and mannitol, along with about 69% of the batch quantity of sucralose and about 33% of the batch quantity of flavor agent (mixed berry), were co-sifted using a No. 40 ASTM.

[0714] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 40 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0715] Step 3: The batch quantity of carnauba wax was sifted using a No. 40 ASTM.

[0716] Step 4: The sifted material of Step 3 was sifted a second time with a No. 40 ASTM and collected in a polybag.

[0717] Step 5: The batch quantity of flavor agent (menthol freeze) was added to the batch quantity of maltitol solution under continuous stirring.

[0718] Step 6: The batch quantities of BHA, BHT, and edetate disodium, along with the remaining batch quantities of flavor agent (mixed berry) and sucralose, were added to the mixture of Step 5 under continuous stirring.

[0719] Step 7: The mixture of Step 6 was stirred until a uniform dispersion was formed.

[0720] Step 8: The intragranular ingredient mixture of Step 2 was mixed for approximately 2- minutes. [0721 ] Step 9: The uniform dispersion of Step 7 was slowly added to the mixture of Step 8 in a thin stream under continuous mixing to form a wet mass.

[0722] Step 10: The wet mass of Step 9 was sifted using a No. 8 ASTM to form wet granules that were collected in a tray.

[0723] Step 11: The wet granules of Step 10 were lubricated using the material of Step 4 for approximately 2-minutes.

[0724] Step 12: The wet granules from Step 11 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) PTFE punch tip, with one of the punch tips having the letter “P” embossed on one side, to form a compressed tablet.

[0725] Step 13: The tablet from Step 12 was sprinkled using the batch quantity of fine sugar.

[0726] Example 32: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 32 below. The ingredients corresponding to Example 32 are tabulated in Table 32 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 32, the active ingredients are acetaminophen and dextromethorphan HBr. Each soft-chew tablet formed by the process of Example 32 has an active strength of acetaminophen of approximately 325 mg and an active strength of dextromethorphan HBr of about 7.30 mg. The amount of each ingredient provided in Table 32 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 32 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0727]

[0728] Procedure - Example 32

[0729] Step 1 : The batch quantities of color agent, flavor agent (cinnamon), flavor agent (apple), citric acid anhydrous, milk powder, dried glucose syrup, sorbitol powder, carboxymethylcellulose calcium, maltodextrin, calcium gluconate, and mannitol, along with about 42% of the batch quantity of carnauba wax, about 38% of the batch quantity of silicified microcrystalline cellulose, and about 67% of the batch quantity of crospovidone, were co-sifted using a No. 40 ASTM. [0730] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 40 ASTM.

[0731] Step 3: The batch quantities of acetaminophen, sodium gluconate, malic acid, and monoammonium glycyrrhizinate, along with about 82% of the batch quantity of sucralose and about 60% of the batch quantity of bitter blocker, were co-sifted using a No. 40 ASTM.

[0732] Step 4: The sifted ingredients of Step 2 and the sifted ingredients of Step 3 were co-sifted using a No. 40 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0733] Step 5: The remaining batch quantities of silicified microcr stalline cellulose and crospovidone were co-sifted with a No. 40 ASTM to form an extragranular ingredient mixture, which was collected in a polybag.

[0734] Step 6: The remaining batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag.

[0735] Step 7: The batch quantity of dextromethorphan HBr, along with the remaining batch quantities of bitter blocker and sucralose, were added to the batch quantity of simethicone under continuous stirring.

[0736] Step 8: The batch quantity of non-crystallizing sorbitol solution was added to the batch quantity of glycerin under continuous stirring.

[0737] Step 9: The mixture of Step 8 was stirred until a uniform dispersion was formed.

[0738] Step 10: The intragranular ingredient mixture of Step 2 was transferred to a rapid mixer granulator (with the impeller set to a slow speed and the chopper off) and mixed for approximately 10-minutes.

[0739] Step 11: The uniform dispersion of Step 7 was slowly added to the mixture of Step 10 in a thin stream (with the impeller set to a slow speed and the chopper on).

[0740] Step 12: The uniform dispersion of Step 9 was slowly added to the mixture of Step 11 in a thin stream (with the impeller set to a slow speed and the chopper on) with intermittent racking to form a wet mass.

[0741] Step 13: The extragranular ingredient mixture of Step 5 was slowly added to the wet mass of Step 12 under continuous mixing.

[0742] Step 14: The material of Step 13 was sifted using a No. 8 ASTM and collected in a tray.

[0743] Step 15: The wet granules of Step 14 were lubricated using the material of Step 6 for approximately 2-minutes. [0744] Step 16: The wet granules from Step 15 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) cast nylon punch tip (length not less than 2.00 mm), with one of the punch tips having the letter “T” embossed on one side, to form a compressed tablet.

[0745] Step 17: The tablet from Step 16 was sprinkled using the batch quantity of sucrose.

[0746] Example 33: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 33 below. The ingredients corresponding to Example 33 are tabulated in Table 33 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 33, the active ingredients are phenylephrine HC1 and diphenhydramine HC1. Each soft-chew tablet formed by the process of Example 33 has an active strength of acetaminophen of approximately 325 mg and an active strength of diphenhydramine HC1 of about 12.50 mg. The amount of each ingredient provided in Table 33 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 33 can be used to make more soft- chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0747]

[0748] Procedure - Example 33

[0749] Step 1 : The batch quantities of calcium gluconate, carboxymethylcellulose calcium, citric acid anhydrous, color agent, dried glucose syrup, flavor agent (cinnamon), flavor agent (apple), maltodextrin, mannitol, milk powder, and sorbitol powder, along with about 54% of the batch quantity of carnauba wax, about 38% of the batch quantity of silicified microcrystalline cellulose, and about 67% of the batch quantity of crospovidone, were co-sifted using a No. 40 ASTM. [0750] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 40 ASTM.

[0751] Step 3: The batch quantities of acetaminophen, sodium gluconate, malic acid, and monoammonium glycyrrhizinate, along with about 60% of the batch quantity of bitter blocker and about 74% of the batch quantity of sucralose, were co-sifted using a No. 40 ASTM.

[0752] Step 4: The sifted ingredients of Step 2 and the sifted ingredients of Step 3 were co-sifted using a No. 40 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0753] Step 5: The remaining batch quantities of silicified microcrystalline cellulose and crospovidone were co-sifted with a No. 40 ASTM to form an extragranular ingredient mixture, which was collected in a polybag.

[0754] Step 6: The remaining batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag.

[0755] Step 7: The batch quantity of diphenhydramine HC1 along with about 12% of the batch quantity of sucralose and the remaining batch quantity of bitter blocker, were added to the batch quantity of simethicone under continuous stirring.

[0756] Step 8: The batch quantity of non-crystallizing sorbitol solution, along with the remaining batch quantity of sucralose, were added to the batch quantity of glycerin under continuous stirring. [0757] Step 9: The mixture of Step 8 was stirred until a uniform dispersion was formed.

[0758] Step 10: The intragranular ingredient mixture of Step 2 was transferred to a rapid mixer granulator (with the impeller set to a slow speed and the chopper off) and mixed for approximately 10-minutes.

[0759] Step 11: The uniform dispersion of Step 7 was slowly added to the mixture of Step 10 in a thin stream (with the impeller set to a slow speed and the chopper on).

[0760] Step 12: The uniform dispersion of Step 9 was slowly added to the mixture of Step 11 in a thin stream (with the impeller set to a slow speed and the chopper on) with intermittent racking to form a wet mass.

[0761] Step 13: The extragranular ingredient mixture of Step 5 was slowly added to the wet mass of Step 12 under continuous mixing.

[0762] Step 14: The material of Step 13 was sifted using a No. 8 ASTM and collected in a tray.

[0763] Step 15: The wet granules of Step 14 were lubricated using the material of Step 6 for approximately 2-minutes. [0764] Step 16: The wet granules from Step 15 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) PTFE punch tip, with one of the punch tips having the letter “T” embossed on one side, to form a compressed tablet.

[0765] Step 17: The tablet from Step 16 was sprinkled using the batch quantity of sucrose.

[0766] Example 34: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 34 below. The ingredients corresponding to Example 34 are tabulated in Table 34 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 34, the active ingredients are dextromethorphan HBr and doxylamine succinate. Each soft-chew tablet formed by the process of Example 34 has an active strength of dextromethorphan HBr of approximately 11 mg and an active strength of doxylamine succinate of about 6.25 mg. The amount of each ingredient provided in Table 34 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 34 can be used to make more soft- chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0767]

[0768] Procedure - Example 34

[0769] Step 1 : The batch quantities of carboxymethylcellulose calcium, dried glucose syrup, flavor agent (menthol freeze), mannitol, milk powder, and sorbitol powder, along with about 42% of the batch quantity of carnauba wax, about 91% of the batch quantity of color agent (FD&C blue), about 91% of the batch quantity of color agent (FD&C red), about 34% of the batch quantity of crospovidone, about 51% of the batch quantity of flavor agent (honey), about 29% of the batch quantity of flavor agent (mixed berry), and about 67% of the batch quantity of silicified microcry stallinc cellulose, were co-siftcd using a No. 40 ASTM.

[0770] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 40 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0771] Step 3: The batch quantities of dextromethorphan HBr, monoammonium glycyrrhizinate, calcium gluconate, and maltodextrin, along with about 50% of the batch quantity of bitter blocker, about 61% of the batch quantity of sucralose, about 60% of the batch quantity of sodium gluconate, and the remaining batch quantities of color agent (FD&C blue) and color agent (FD&C red), were co-sifted with a No. 60 ASTM and collected in a polybag.

[0772] Step 4: The remaining batch quantities of crospovidone, flavor agent (honey), flavor agent (mixed berry), and silicified microcrystalline cellulose were co-sifted with a No. 40 ASTM to form an extragranular ingredient mixture, which was collected in a polybag.

[0773] Step 5: The remaining batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag.

[0774] Step 6: The batch quantity of doxylamine succinate, along with the remaining batch quantities of bitter blocker and sodium gluconate, were added to the batch quantity of simethicone under continuous stirring.

[0775] Step 7: The batch quantity of non-crystallizing sorbitol solution, along with the remaining batch quantity of sucralose, were added to the batch quantity of glycerin under continuous stirring. [0776] Step 8: The mixture of Step 7 was stirred until a uniform dispersion was formed.

[0777] Step 9: The intragranular ingredient mixture of Step 2 was transferred to a rapid mixer granulator (with the impeller set to a slow speed and the chopper off) and mixed for approximately 10-minutes.

[0778] Step 10: The uniform dispersion of Step 6 was slowly added to the mixture of Step 9 in a thin stream (with the impeller set to a slow speed and the chopper on).

[0779] Step 11: The uniform dispersion of Step 8 was slowly added to the mixture of Step 10 in a thin stream (with the impeller set to a slow speed and the chopper on) with intermittent racking to form a wet mass.

[0780] Step 12: The extragranular ingredient mixture of Step 4 was slowly added to the wet mass of Step 11 under continuous mixing. [0781 ] Step 13: The material of Step 3 was added to the material of Step 12 under continuous mixing.

[0782] Step 14: The material of Step 13 was sifted using a No. 8 ASTM to form wet granules that were collected in a tray.

[0783] Step 15: The wet granules of Step 14 were lubricated using the material of Step 5 for approximately 2-minutes.

[0784] Step 16: The wet granules from Step 15 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) PTFE punch tip, with one of the punch tips having the letter “R” embossed on one side, to form a compressed tablet.

[0785] Step 17: The tablet from Step 16 was coated using the batch quantity of sucrose.

[0786] Example 35: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 35 below. The ingredients corresponding to Example 35 are tabulated in Table 35 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 35, the active ingredients are guaifenesin and dextromethorphan HBr. Each soft-chew tablet formed by the process of Example 35 has an active strength of guaifenesin of approximately 100 mg and an active strength of dextromethorphan HBr of about 7.30 mg. The amount of each ingredient provided in Table 35 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 35 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0787]

[0788] Procedure - Example 35

[0789] Step 1: The batch quantities of calcium gluconate, croscarmellose sodium, flavor agent (orange), guaifenesin, maltodextrin, and sodium bicarbonate, along with about 60% of the batch quantity of amino methacrylate copolymer, about 60% of the batch quantity of bitter blocker, about 67% of the batch quantity of carnauba wax, about 75% of the batch quantity of dried glucose syrup, about 75% of the batch quantity of milk powder, about 47% of the batch quantity of monoammonium glycyrrhizinate, about 67% of the batch quantity of partially pregelatinized starch, about 50% of the batch quantity of silicified microcrystalline cellulose, and about 16% of the batch quantity of sucralose, were co-sifted using a No. 40 ASTM.

[0790] Step 2: The sifted ingredients of Step 1 were sifted a second time with a No. 40 ASTM to form an intragranular ingredient mixture, which was collected in a polybag.

[0791] Step 3: The batch quantity of sodium gluconate, along with about 70% of the batch quantity of flavor agent (menthol freeze), about 27% of the batch quantity of monoammonium glycyrrhizinate, about 69% of the batch quantity of sucralose, and the remaining batch quantities of silicified microcrystalline cellulose, milk powder, partially pregelatinized starch, and dried glucose syrup, were co-sifted with a No. 40 ASTM to form an extragranular ingredient mixture, which was collected in a polybag.

[0792] Step 4: The remaining batch quantity of carnauba wax was sifted using a No. 60 ASTM and collected in a polybag.

[0793] Step 5: The batch quantity of dextromethorphan HBr, along with about 20% of the batch quantity of bitter blocker, were added to the batch quantity of simethicone under continuous stirring.

[0794] Step 6: The batch quantities of carboxymethylcellulose calcium, color agent (FD&C yellow), ethanol, flavor agent (peppermint), polyvinylpyrrolidone K30, neotame, sodium chloride, and zinc gluconate, along with the remaining batch quantities of amino methacrylate copolymer, bitter blocker, flavor agent (menthol freeze), monoammonium glycyrrhizinate, and sucralose, were added to the batch quantity of glycerin under continuous stirring.

[0795] Step 7: The mixture of Step 6 was stirred until a uniform dispersion was formed.

[0796] Step 8: The intragranular ingredient mixture of Step 2 was transferred to a rapid mixer granulator (with the impeller set to a slow speed and the chopper off) and mixed for approximately 10-minutes.

[0797] Step 9: The uniform dispersion of Step 5 was slowly added to the mixture of Step 8 in a thin stream (with the impeller set to a slow speed and the chopper on). [0798] Step 10: The uniform dispersion of Step 7 was slowly added to the mixture of Step 9 in a thin stream (with the impeller set to a slow speed and the chopper on) with intermittent racking to form a wet mass.

[0799] Step 11: The extragranular ingredient mixture of Step 3 was slowly added to the wet mass of Step 10 under continuous mixing.

[0800] Step 12: The material of Step 11 was sifted using a No. 8 ASTM and collected in a tray.

[0801] Step 13: The wet granules of Step 12 were lubricated using the material of Step 4 for approximately 2-minutes.

[0802] Step 14: The wet granules from Step 13 were compressed using a rotary tablet press equipped with upper and lower punches each including a round-shaped (diameter of approx. 20mm) PTFE punch tip, with one of the punch tips having the letter “T” embossed on one side, to form a compressed tablet.

[0803] Example 36: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 36 below. The ingredients corresponding to Example 36 are tabulated in Table 36 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 36, the active ingredient is simethicone. Each soft-chew tablet formed by the process of Example 36 has an active strength of simethicone of approximately 250 mg. The amount of each ingredient provided in Table 36 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 36 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0804]

[0805] Procedure - Example 36

[0806] Step 1: The batch quantities of carnauba wax, color agent (FD&C red), croscarmellose sodium, crospovidone, dried glucose syrup, mannitol, milk powder, partially pregelatinized starch, and sorbitol powder, along with about 56% of the batch quantity of flavor agent (mixed berry), were placed in a rapid mixer granulator under continuous mixing with the impeller speed set at 50 RPM and the chopper off.

[0807] Step 2: The batch quantity of maltitol solution was added to the batch quantity of glycerin under continuous stirring.

[0808] Step 3: The batch quantity of sucralose was added to the mixture of Step 2 under continuous stirring.

[0809] Step 4: The batch quantity of citric acid anhydrous, along with the remaining batch quantity of flavor agent (mixed berry), were added to the mixture of Step 3 under continuous stirring. [0810] Step 5: The mixture of Step 4 was stirred until a uniform dispersion was formed. [0811 ] Step 6: The batch quantity of simethicone was slowly added to the mixture of Step 1 in a thin stream under continuous mixing with the impeller speed set at 100 RPM and the chopper speed set at 1200 RPM.

[0812] Step 7: The material of Step 6 was mixed for an additional 2.5-minutes with the impeller speed set at 100 RPM and the chopper speed set at 1200 RPM.

[0813] Step 8: The uniform dispersion of Step 5 was slowly added to the material of Step 7 in a thin stream under continuous mixing (with the impeller speed set at 100 RPM and the chopper speed set at 1200 RPM) with intermittent racking to form a wet mass.

[0814] Step 9: The wet mass of Step 8 was passed through a cone mill to form milled granules. The cone mill was fitted with a 4mm square shaped screen.

[0815] Step 10: The granules of Step 9 were passed through a cone mill to form milled wet granules. The cone mill was fitted with a 3mm square shaped screen.

[0816] Step 11: The wet granules from Step 10 were compressed using a rotary tablet press equipped with upper and lower punches each including a square-shaped (approx. 15.3mm by 15.3mm) PTFE punch tip, with one of the punch tips having the having the number “7” embossed on one side, to form a compressed tablet.

[0817] Step 12: The tablet from Step 11 was coated using the batch quantity of sugar.

[0818] Example 37: A process for making soft-chew tablets in accordance with certain aspects of the present invention is provided in Example 37 below. The ingredients corresponding to Example 37 are tabulated in Table 37 with the amount of each ingredient used in the process given in percent-by-weight and in milligrams. In Example 37, the active ingredients are simethicone. Each soft-chew tablet formed by the process of Example 37 has an active strength of simethicone of approximately 250 mg. The amount of each ingredient provided in Table 37 corresponds to the formation of a single soft-chew tablet; however, as should be understood by those having ordinary skill in the art, the principles of Example 37 can be used to make more soft-chew tablets by proportionally increasing the amount of the ingredients as necessary to produce the desired quantity of soft-chew tablets.

[0819]

[0820] Procedure - Example 37

[0821] Step 1: The batch quantities of crospovidone, dried glucose syrup, mannitol, milk powder, and sorbitol powder, along with about 56% of the batch quantity of flavor agent (mixed berry), were placed in a rapid mixer granulator under continuous mixing with the impeller speed set at 50 RPM and the chopper off.

[0822] Step 2: The batch quantity of maltitol solution was added to the batch quantity of glycerin under continuous stirring.

[0823] Step 3: The batch quantity of sucralose was added to the mixture of Step 2 under continuous stirring.

[0824] Step 4: The batch quantities of color agent (FD&C red) and citric acid anhydrous, along with the remaining batch quantity of flavor agent (mixed berry), were added to the mixture of Step 3 under continuous stirring.

[0825] Step 5: The mixture of Step 4 was stirred until a uniform dispersion was formed.

[0826] Step 6: The batch quantity of simethicone was slowly added to the mixture of Step 1 in a thin stream under continuous mixing with the impeller speed set at 100 RPM and the chopper speed set at 1200 RPM.

[0827] Step 7: The material of Step 6 was mixed for an additional 2.5-minutes with the impeller speed set at 100 RPM and the chopper speed set at 1200 RPM. [0828] Step 8: The uniform dispersion of Step 5 was slowly added to the material of Step 7 in a thin stream under continuous mixing (with the impeller speed set at 100 RPM and the chopper speed set at 1200 RPM) with intermittent racking to form a wet mass.

[0829] Step 9: The batch quantities of carnauba wax, croscarmellose sodium, and partially pregelatinized starch were added to the wet mass of Step 8 under continuous mixing (with the impeller speed set at 100 RPM and the chopper speed set at 1200 RPM).

[0830] Step 10: The material of Step 9 was passed through a cone mill to form milled granules. The cone mill was fitted with a 4mm square shaped screen.

[0831] Step 11: The wet granules of Step 10 were passed through a cone mill to form milled granules. The cone mill was fitted with a 4mm square shaped screen.

[0832] Step 12: The wet granules from Step 11 were compressed using a rotary tablet press equipped with upper and lower punches each including a square-shaped (approx. 15.3mm by 15.3mm) PTFE punch tip, with one of the punch tips having the having the number “7” embossed on one side, to form a compressed tablet.

[0833] Step 13: The tablet from Step 12 was coated using the batch quantity of sugar.

ANALYSIS

[0834] The results of a product characterization analysis performed on the soft chewable tablets formed in accordance with the Examples provided herein is summarized in Table D 1. Table D 1 provides information pertaining to the product characterization analysis of the soft chewable tablets formed in accordance with the corresponding Examples provided therein shortly after compression.

[0835]

[0836] A texture analysis was performed on the soft chew tablets formed in accordance with the Examples provided therein using a CT3 Texture Analyzer (Brookfield Engineering) configured as provided in Table D2. The texture analysis was performed shortly after formation of the tablets. Texture parameters derived from the texture analysis are provided in Tables D3 and D4, including values for: average hardness cycle 1 (“AHC1”) given in grams; average adhesiveness (“AAd”) given in millijoules; average fracturability with 1% load sensitivity (“AF1”) given in grams; average hardness cycle 2 (“AHC2”) given in grams; average cohesiveness (“ACo”) given in millimeters; average springiness (“ASp”) given in millimeters; average gumminess (“AGu”) given in grams; and average chewiness (“ACh”) given in millijoules. Additional details relating to the foregoing parameters and texture analyzer can be found in the Operating Instructions for the CT3 Texture Analyzer (Manual No. M08-372-F1116), which is incorporated herein by reference in its entirety. It should be understood that the present invention is not limited to parameters measured by a specific instrument and that other instruments may be used without departing from the spirit of the present invention.

[0837]

[0838] [0839]

[0840] A disintegration analysis of the soft chew tablets made in accordance with the Examples provided herein was performed in accordance with U.S. Pharmacopeia General Chapter <701> Disintegration. In each instance, the disintegration analysis was performed using nine hundred milliliters (900 ml) of water at a temperature of about 37 °C (± 2 °C) and a sample size of six (6) soft chew tablets. Table D5 provides information pertaining to the disintegration analysis of the soft chew tablets formed in accordance with the corresponding Examples provided therein shortly after the compression step. Table D5 includes values for disintegration time (“DT”) provided in minutes.

[0841]

[0842] The results of a particle size analysis of the tablets are summarized in Table D6. [0843]

[0844] The results of a flow property analysis of the tablets are summarized in Table D7.

[0845]

[0846] Table D8 provides information pertaining to the impurity analysis of the soft chew tablets formed in accordance with the corresponding Examples provided therein after being stored for a number of days (SD) at a temperature of 40 °C and a relative humidity of 75%. Table D8 includes values for: highest known impurity percentage (“HKI %”); highest known impurity percentage (“HUI %”); and percentage of total impurity (“TI %”). [0847]

[0848] Tabic D9 provides information pertaining to the impurity analysis of the soft chew tablets formed in accordance with the corresponding Examples provided therein after being stored for a number of days (SD) at a temperature of 60 °C and a relative humidity of 60%. Table D9 includes values for: highest known impurity percentage (“HKI %”); highest known impurity percentage

(“HUI %”); and percentage of total impurity (“TI %”).

[0849]

[0850] Table D10 provides assay percentages (“Asy %”) from the impurity analysis of the soft chew tablets formed in accordance with the corresponding Examples provided therein after being stored for a number of days (SD) at a temperature of 40 °C and a relative humidity of 75%.

[0851]

[0852] Table Dll provides assay percentages (“Asy %”) from the impurity analysis of the soft chew tablets formed in accordance with the corresponding Examples provided therein after being stored for a number of days (SD) at a temperature of 60 °C and a relative humidity of 60%.

[0853]

[0854] A microbiological characterization analysis of the soft chew tablets manufactured in accordance with the Examples provided herein was performed in accordance with USP general chapter <1112>. Table D12 provides information pertaining to the microbiological characterization analysis of the soft chew tablets formed in accordance with the corresponding Examples provided therein shortly after formation and after being stored for a number of days (SD) at a temperature of 40 °C and a relative humidity of 75%. Table D12 includes values for water content and water activity (aw).

[0855]

[0856] A texture analysis was performed on the soft chew tablets formed in accordance with the corresponding Examples provided therein using a CT3 Texture Analyzer (Brookfield Engineering) configured as provided in Table D2. The texture analysis was performed after the tablets had been stored for a number of days (SD) at a temperature of 40 °C and a relative humidity of 75%. Texture parameters derived from the texture analysis are provided in Tables D13 and D 14, including values for: average hardness cycle 1 (“AHC1”) given in grams; average adhesiveness (“AAd”) given in millijoules; average fracturability with 1% load sensitivity (“AF1”) given in grams; average cohesiveness (“ACo”) given in millimeters; average springiness (“ASp”) given in millimeters; average gumminess (“AGu”) given in grams; and average chewiness (“ACh”) given in millijoules.

[0857]

[0858]

ADDITIONAL CONSIDERATIONS

[0859] As used herein, the term “specification” refers to all pails of the written description, including the working examples, and the claims of the present patent application.

[0860] As used in this specification, the phrase “and/or,” when used in a list of two or more items, means that any one of the listed items can be employed by itself or any combination of two or more of the listed items can be employed. For example, if a composition is described as containing or excluding components A, B, and/or C, the composition can contain or exclude A alone; B alone; C alone; A and B in combination; A and C in combination; B and C in combination; or A, B, and C in combination.

[0861] As used in this specification, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having” or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, a process, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.

[0862] Approximating language, as used in this specification, may be applied to modify any quantitative representation that could permissibly vary without resulting in a change in the basic function to which it is related. Accordingly, a value modified by a term or terms, such as “about,” “approximately,” and “substantially” are not to be limited to the precise value specified. In at least some instances, the approximating language may correspond to the precision of an instrument for measuring the value. In this specification, range limitations may be combined and/or interchanged. Such ranges are identified and include all the sub-ranges contained therein unless the context or language indicates otherwise.

[0863] With respect to the use of substantially any plural and/or singular terms used in this specification, those having skill in the art can translate from the plural to the singular and/or from the singular to the plural as is appropriate to the context and/or application. The various singular/plural permutations may be expressly set forth herein for the sake of clarity.

[0864] In this specification, a numerical range indicated by using “to” or “to about” shows a range including numerical values written before and after “to” or “to about” as a minimum value and a maximum value, respectively. In this specification numerical ranges are used to quantify certain parameters relating to various embodiments. It should be understood that when numerical ranges are provided, such ranges are to be construed as providing literal support for claim limitations that only recite the lower value of the range as well as claim limitations that only recite the upper value of the range. For example, a disclosed numerical range of about 10 to about 100 provides literal support for a claim reciting “greater than about 10” (with no upper bounds) and a claim reciting “less than about 100” (with no lower bounds). Furthermore, in the case of all the relative or percentage amount information, particularly weight-related amount information, that this information is to be selected by a person skilled in the art, within the scope of the present invention, in such a manner that the sum of the respective ingredients, active ingredients, additives or ancillary substances or the like always come up to 100% or 100 %w/w.

[0865] With respect to the claims below, if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases “at least one” and “one or more” to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles “a” or “an” limits any particular claim containing such introduced claim recitation to embodiments containing only one such recitation, even when the same claim includes the introductory phrases “one or more” or “at least one” and indefinite articles such as “a” or “an” (e.g., “a” and/or “an” should be interpreted to mean “at least one” or “one or more”); the same holds true for the use of definite articles used to introduce claim recitations. In addition, even if a specific number of an introduced claim recitation is explicitly recited, it should be understood that such recitation means at least the recited number (e.g., the bare recitation of “two recitations,” without other modifiers, means at least two recitations, or two or more recitations). In those instances where a convention analogous to “at least one of A, B, and C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “a system having at least one of A, B, and C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.). In those instances where a convention analogous to “at least one of A, B, or C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “a system having at least one of A, B, or C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B , and C together, etc.).

[0866] In this written description, references to “one embodiment”, “an embodiment”, or “embodiments” mean that the feature or features being referred to are included in at least one embodiment of the of the present invention. Separate references to “one embodiment”, “an embodiment”, or “embodiments” in this written description do not necessarily refer to the same embodiment and are also not mutually exclusive unless so stated and/or except as will be readily apparent to those skilled in the art from the description. For example, a feature, structure, act, etc. described in one embodiment may also be included in other embodiments, but is not necessarily included. Thus, the present invention encompasses a variety of combinations and/or integrations of the specific embodiments described in the specification and any suitable combination of the previously described embodiments may be made without departing from the spirit of the present invention.

[0867] This written description is to be construed as exemplary only and does not describe every possible embodiment since describing every possible embodiment would be impractical. Numerous alternative embodiments may be implemented, using either current technology or technology developed after the filing date of this patent application, which would still fall within the scope of the present invention.

[0868] The inventors hereby state their intent to rely on the Doctrine of Equivalents to determine and assess the reasonably fair scope of the present invention as pertains to anything not materially departing from but outside the literal scope of the invention as set forth herein.

[0869] Having thus described various embodiments of the invention, what is claimed as new and desired to be protected by Letters Patent includes the following: