Field of disclosure

The invention relates to a method for drying capsules, particularly microcapsules, as well as an assembly of capsules, in particular microcapsules.

5 Background, prior art

Capsules, particularly microcapsules with particle sizes of less than 1 mm, have found widespread application in the fields of pharmaceuticals, cosmetics, diagnostics, food and material science, among others. The production of capsules often involves the use of liquids, particularly solvents. As an example, capsules may be produced from an emulsion0 of monodisperse droplets in a continuous phase. Many known manufacturing processes yield the product capsules as a solution, suspension or emulsion in a liquid, particularly water. However, for certain applications, it is desirable to reduce the amount of liquid in the product. In particular, certain applications require the capsules to be dried to a solid, ideally with a high flowability. Free-flowing capsules are also advantageous because they are easy to handle and process.

Summary of disclosure

Known processes for drying solutions, suspensions or emulsions of capsules in a liquid such as water involve spray-drying, freeze-drying or the use of a fluidized bed. A further approach involves heating, typically at temperatures exceeding 60 °C. However, one0 problem with known drying processes is that they lead to at least partial destruction and/or leakage of the capsules. This may, for example, be associated with loss of active ingredient encapsulated in the capsules. A further problem is particle aggregation, which sometimes limits the degree to which the capsules may be dried. A further problem is that many drying processes significantly affect various physical properties of the capsules, such as their volume or brittleness, which may affect the stability of the capsules after drying as well as their biological or physicochemical properties.

A further deficiency identified in the prior art is that even after a successful drying process, the resulting plurality of capsules may be instable, which may lead to a diminished shelf life and/or reduced activity. Another deficiency is that the plurality of capsules obtained after drying using known methods often has a low flowability, which significantly restricts the application and usability and which also reduces the ease with which the plurality of capsules may be handled.

It is therefore a general object to advance the state of the art of drying capsules, in particular microcapsules and preferably to overcome the disadvantages of the prior art fully or partially. It is a further general object to advance the state of the art of providing an assembly of such capsules. In advantageous embodiments, a method for drying capsules is provided which operates under mild conditions, in particular avoiding significant mechanical stress. In advantageous embodiments, a method of drying capsules is provided which allows the manufacturing of an assembly of capsules displaying a high degree of flowability. In advantageous embodiments, an assembly of capsules is provided which displays a high degree of flowability and advantageously also displays a long shelf life.

In a first aspect, the general object is achieved by an assembly of capsules, in particular microcapsules. The assembly of capsules comprises a plurality of capsules, in particular microcapsules. Each capsule comprises a liquid core and a water-insoluble matrix shell encasing the liquid core. The assembly of capsules further comprises a drying agent, wherein the majority by weight of the drying agent is outside the matrix shell of the capsules. In some embodiments, the liquid core is an oil core. In further embodiments, the liquid core is an aqueous core. In still further embodiments, the liquid core is an oil-water mixture.

One advantage of the assembly of capsules of the first aspect of the disclosure is that it displays a high degree of flowability. A further advantage is its high stability, which translates into a long shelf life of the assembly of capsules. In particular, the capsules comprised in the assembly of capsules display a high stability. Without wishing to be bound to a theory, the stability may in part be due to the presence of the drying agent, which may act as a stabilizer. Stability may relate to mechanical stability and/or to resistance against degradation, such as microbial degradation.

The assembly of capsules of the first aspect can be obtained by the method for drying capsules as described in any of the embodiments herein.

As used herein, the term “microcapsule” generally refers to a capsule with a particle size of less than 4 mm, preferably between 1 pm and < 4 mm, more preferably between 1 pm and < 1 mm. Concomitantly, a microdroplet has a droplet size, i.e. a diameter less than 4 mm, preferably between 1 pm and < 4 mm, more preferably between 1 pm and < 1 mm and a microchannel has a diameter of typically less than 4 mm, preferably between 1 pm and < 4 mm, more preferably between 1 pm and < 1 mm.

In some embodiments, the liquid core has a viscosity of less than 1O ²⁰ Pa*s, such as less than 1O ¹⁰ Pa*s, such as less than 10 ³ Pa*s. In some embodiments, the liquid core has a viscosity from 10' ⁶ Pa*s to 10 ³ Pa*s, such as from 10' ⁵ Pa*s to 10 ² Pa*s, such as from 10' ⁴ Pa*s to 50 Pa*s.

As used herein, water-insoluble generally means that the matrix shell has a solubility in water at 25 °C and 1 bar of less than 2 g/L, preferably less than 1 g/L, more preferably less than 0.5 g/L, even more preferably less than 0.1 g/L.

It is understood that the plurality of capsules typically comprises at least 10 capsules, particularly at least 100 capsules, particularly at least 1000 capsules. The plurality of capsules and the drying agent are typically randomly and/or evenly distributed throughout the assembly.

It is understood that the water-insoluble matrix shell typically encases the liquid core such that the liquid core is contained and maintained inside the capsule. Typically, the water- insoluble matrix shell completely encases the liquid core. Typically, the liquid core is a liquid core at 25 °C and 1 bar. Typically, the water-insoluble matrix shell is solid at 25 °C and 1 bar. In some embodiments, the matrix shell of a capsule has a shell thickness and comprises an inner shell layer and an outer shell layer. The inner shell layer faces the liquid core of the capsule.

In an embodiment, the thickness of each matrix shell is less than 200 micrometers, particularly less than 130 micrometers, more particularly from 40 micrometers to 110 micrometers. This ensures that the capsules are sufficiently stable whilst at the same time ensuring a large volume for the liquid core.

It is understood that each capsule defines an inside and an outside, wherein the inside is encapsulated by the matrix shell of the capsule. The majority by weight of the drying agent is outside the matrix shell of the capsules. This means that the majority by weight of the drying agent is not inside any capsule. In an embodiment, at least 60 wt-%, particularly at least 70 wt-%, more particularly at least 80 wt-%, more particularly at least 90 wt-%, more particularly at least 95 wt-%, more particularly at least 98 wt-%, more particularly at least 99 wt-%, more particularly all of the drying agent is outside the matrix shell of the capsules.

In a typical embodiment, the matrix shell of the capsules is impermeable to the drying agent. Typically, impermeable means that less than 5 wt-%, more particularly less than 1 wt-% of the drying agent permeates the matrix shell of the capsule at 25 °C at 1 bar within 24 hours.

In an embodiment, the weight of the drying agent is less than 15 wt-% relative to the overall weight of the plurality of capsules, preferably less than 7 wt-%, more preferably from 3 wt- % to 7 wt-%. These embodiments were found to strike an advantageous balance between minimizing the amount of drying agent on the one hand and ensuring a high degree of flowability and high stability of the assembly of capsules on the other hand.

In an embodiment, the drying agent is an inorganic drying agent, such as CaCCh, silica, MgSC Na2SC>4, KOH, CaO, CaCh, CaSO4, molecular sieves. In a preferred embodiment, the drying agent is water-insoluble, which means that the solubility in water is less than 1 g/L, preferably less than 0.2 g/L, more preferably less than 50 mg/L at 25 °C. In preferred embodiments, the drying agent is selected from CaCCh, CaSC>4, silica and/or a stearate salt. In some embodiments, the drying agent is selected from CaCCh, CaSC>4 and silica, preferably CaCCh. It is understood that the drying agent may be anhydrous or may be at least, or even fully, hydrated. As an example, in an embodiments in which the drying agent is CaCCh, the drying agent may comprise a hydrated form of the drying agent, e.g., CaCOs’fW and/or CaCO3*6H ₂ O. One advantage of these drying agents, particularly calcium carbonate, is that they were found to ensure a particularly high degree of flowability. A further advantage is that these drying agents render the assembly of capsule highly stable.

Molecular sieves comprise zeolites. Zeolites are aluminosilicate minerals having a pore size of less than 2 nm, preferably from 0.1 nm to 1 nm.

In an embodiment, the drying agent has a particle size of less than 100 micrometers, particularly less than 60 micrometers, more particularly less than 20 micrometers, more particularly less than 10 micrometers. One advantage of these embodiments is that they ensure a high stability and a high degree of flowability of the assembly of capsules. Additionally, these particle sizes are easily obtained using readily available sources of drying agent, such as calcium carbonate. The particle size of the drying agent and/or of the capsules may for example be determined by sieving or advantageously by dynamic light scattering.

In an embodiment, the drying agent has a solubility in water of less than 1 g/L, preferably less than 0.2 g/L, more preferably less than 50 mg/L at 25 °C. These solubility ranges were found to enhance the shelf life, stability and flowability of the assembly of capsules.

In an embodiment, the assembly of capsules has an angle of repose of less than 45°, preferably less than 42°, more preferably from 34° to 41°. The low angle of repose demonstrates the high degree of flowability of the assembly of capsules. The angle of repose (a) is measured at 25 °C and 1 bar by passing a sample of the assembly of capsules through a funnel directed to a horizontal surface, which resulted in a conical pile of the assembly of capsules being formed on the horizontal surface. The conical pile had a circular base surface with a diameter of B and a height H. The angle of repose is thus defined as: wherein a denotes the angle of repose. The funnel has a height of 170 mm and comprises a top section and a bottom section. The top section and the bottom section are each conical frustrum. The top section of the funnel has a height of 70 mm and a diameter of 112 mm at the top and a diameter of 20 mm at the bottom. The bottom section of the funnel, which is directly adjacent to the top section of the funnel, has a height of 100 mm and a top diameter of 20 mm and a bottom diameter of 4 mm.

In an embodiment, the assembly of capsules has a flowability of from 0.1 g/sec to 0.8 g/sec according to the flowability test method described herein.

The flowability test method is as follows: the assembly of capsules is allowed to flow through a tube onto a balance, wherein the tube has a height of 8.2 cm and a distance of 10 cm from the balance, wherein the tube is made of PETG and has a top end through which the assembly of capsules is entered into the tube and a bottom end arranged towards the balance, wherein the tube has an inner diameter which tapers evenly from the top end to the bottom end, wherein the top end is circular and has an inner diameter of 9 mm, wherein the bottom end is circular and has an inner diameter of 4.5 mm.

In an embodiment, the assembly of capsules has a compressibility, as measured according to Carr’s Index, of below 17, particularly up to 16, more particularly from 6 to 16. In some embodiments, the assembly of capsules has a compressibility, as measured according to Carr’s Index, of up to 12, particularly from 6 to 12. In an embodiment, the assembly of capsules has a compressibility, as measured according to Hausner’s Ratio, of less than 1.25, particularly from 1.00 to 1.20. In an embodiment, the assembly of capsules has a compressibility of up to 1.70, such as from 1.00 to 1.70. The measurements according to both Carr’s Index and Hausner’s Ratio were performed according to US Pharmacopeia standard USP616, in its version as of August 1 , 2015. A 100 mL cylinder was used, an initial volume of 80 mL was used and the tapped density tester ERWEKA SVM 202 was used. 10 strokes were applied, followed by 500 strokes, followed by 1250 strokes. If the difference in volume from application of 500 strokes to application of 1250 strokes was more than 1 mL, an additional 1250 strokes were applied.

In an embodiment, each capsule has a diameter of less than 3000 micrometers, particularly from 1 micrometer to 1000 micrometers, more particularly from 50 micrometers to 1000 micrometers, more particularly from 50 micrometers to 700 micrometers, particularly from 50 micrometers to 500 micrometers. It is understood that the diameter of a capsule refers to the largest distance between any two points on the matrix shell of a capsule, in particular between any two points on the outer shell layer of the matrix shell of a capsule. As an example, if a capsule has an oval shape, the diameter of the capsule refers to the largest distance between any two points on the matrix shell of the capsule. It was found that the assembly of capsules having capsules of the indicated diameter still displays a high degree of flowability. Surprisingly, aggregating and/or sticking together of capsules is minimized or even avoided completely. Additionally, it was found that the assembly of capsules having capsules of the indicated diameter still displays a high degree of stability even though such capsules are particularly instable when kept using previously known approaches.

In an embodiment, the capsules have a sphericity index from 0.7 to 1 , particularly from 0.8 to 0.98. One advantage of these embodiments is that they allow the assembly of capsules to have an advantageous density. In particular, the sphericity may allow an advantageous arrangement and stacking with the drying agent. Additionally, the indicated sphericity ranges may be associated with high capsule stability.

In an embodiment, the coefficient of variation with respect to the capsule diameter distribution is less than 10%, particularly from 1% to 8% One advantage of these embodiments is that the capsules in the assembly of capsules have similar properties, including regarding their capacity to encapsulate a liquid core, such as an oil core, and their stability. The small variation with respect to the capsuled diameter may also positively impact flowability of the assembly of capsules.

In an embodiment, the weight of surface oil on the capsules is less than 10 wt% relative to the weight of the capsules, particularly less than 5 wt%, more particularly from 0.01 wt% to 3 wt%. It is understood that the surface oil is arranged outside the matrix shell of the capsules. In particular, the surface oil of a capsule is typically arranged on the outer shell layer of the capsules facing the outside of the matrix. The indicated ranges of the weight of surface oil ensure an advantageous polarity of the capsules. The indicated ranges of the weight of surface oil may also contribute to enhanced flowability of the assembly of capsules, possibly due to preventing aggregation of capsules.

The weight of surface oil on the capsules may, for example, be determined using the following procedure: 0.2 g of the assembly of capsules is mixed with 5 mL of hexane, preferably by gently stirring for 2 minutes using a spatula, followed by filtering the mixture through a filter paper (grade 602h with a pore size of less than 2 micrometer). The filtrate solution is left to evaporate at 23 °C and 1 bar until constant weight was obtained. The resulting constant weight corresponds to the weight of surface oil. Optionally, the filtrand may be rinsed with hexane during the step of filtering the mixture.

In an embodiment, the matrix shell comprises a polyelectrolyte, in particular a gelled polyelectrolyte. As an example, at least 50 wt-%, particularly at least 60 wt-%, more particularly at least 70 wt-%, more particularly at least 80 wt-%, more particularly at least 90 wt-%, more particularly at least 95 wt-%, more particularly at least 98 wt-%, more particularly 100 wt-% of the matrix shell may be made of the polyelectrolyte, such as the gelled polyelectrolyte. In an embodiment, the polyelectrolyte is a polysaccharide or suitable salt thereof. A suitable salt is a salt form which is water-insoluble, as defined above with respect to the water-insoluble matrix shell. As an example, the polysaccharide salt may be an alkaline or earth alkaline polysaccharide salt. Typically, polysaccharide salts are composed of an anionic polysaccharide component and a suitable counter cation. The suitable counter cation is preferably chosen such that the polysaccharide salt is water-insoluble, as defined above. As an example, the counter cation may be selected from K, Mg, Sr, Ca, Na, Zn, Fe salts, among others. Preferably, the counter cation is selected from K, Mg, Sr or Ca salts, preferably Ca or Mg salts, more preferably Ca salts. The polysaccharides are preferably selected from chitosan, cellulose, alginate, particularly sodium alginate, carrageenan, agar, agarose, pectins, gellan, starch, and the like. Preferred polysaccharides are alginate, preferably calcium alginate, chitosan, carrageenan and cellulose, more preferably alginate, preferably calcium alginate, chitosan. In some embodiments, the polysaccharides may be solubilized by adjusting the pH, for example by basifying the pH of the aqueous shellforming solution.

In some embodiments, the water-insoluble matrix comprises, e.g. in addition to the polyelectrolyte, an additional biopolymer as structural stabilizer, such as pectin (for example GENU® pectin type LM-104 AS-FG). Preferably, the additional biopolymer may also be able to form the matrix shell. In certain embodiments, the additional biopolymer may be solid biopolymer particles, e.g. starch. Providing such an additional biopolymer and in particular solid biopolymer particles increases the mechanical strength of the generated capsules and thus avoids breaking of the capsules during production, curing and particularly drying. It further allows fine-tuning of the water binding capacity of the polymers. In some embodiments, the water-insoluble matrix comprises from 5 wt-% to 20 wt-%, preferably from 5 wt-% to 15 wt-%, more preferably 10 wt-%, starch, such as potato starch. In some embodiments, the water-insoluble matrix comprises from 5 wt-% to 20 wt-%, preferably from 5 wt-% to 15 wt-%, more preferably 10 wt-%, dextrin. These embodiments ensure a high degree of flowability, which may possible be the result of efficient water binding. Additionally, these embodiments contribute to capsule elasticity.

In an embodiment, the assembly of capsules has a residual water content of less than 5 wt- %, preferably less than 3 wt-%, more preferably less than 1 wt-%, more preferably less than 0.5 wt-%, more preferably less than 0.1 wt-%. These were found to ensure a high degree of flowability. The residual water content refers in particular to the water that is outside the matrix shell of the capsules. It is understood that residual water refers to free water molecules and does not include water molecules that are bound, e.g. coordinately, to the drying agent. As an example, residual water does not include the one, respectively six, water molecules present in e.g. CaCOs’ W and/or CaCO3*6H ₂ O.

In an embodiment, the assembly of capsules has a water activity of up to 0.7, particularly from 0.3 to 0.7, particularly from 0.4 to 0.6. In an embodiment, the water activity is less than 0.6, particularly from 0.42 to 0.58. The water activity may be measured at 25 °C using the LabMaster-aw Neo by Novasina AG. One advantage of the indicated water activity is that the microbial growth is minimal.

In a second aspect, the general object is achieved by a method for drying capsules, in particular to obtain an assembly according to any of the embodiments of the first aspect of the present disclosure. The method comprises providing a wet raw composition comprising water and a plurality of capsules, in particular microcapsules, wherein each capsule comprises a liquid core and a water-insoluble matrix shell encasing the liquid core. The method further comprises treating the wet raw composition with a drying composition at a temperature of less than 60 °C, wherein the drying composition comprises a drying agent, and, optionally, removing at least a portion of the drying agent, to obtain an assembly of capsules. It is understood that the term “wet raw composition” refers to a composition which has a higher water content, i.e. higher amount of free water molecules than the assembly obtained by the method, i.e. the dried assembly.

The method for drying capsules allows obtaining an assembly of capsules according to the first aspect of the present disclosure. As a result, any embodiment described for the assembly of capsules is also an embodiment of the method for drying capsules. As an example, the embodiments of the capsules, the drying agent, the plurality of capsules, the assembly of capsules, and the matrix shell of the capsules previously described in the context of the first aspect also apply to the method for drying capsules according to the second aspect. Furthermore, the advantages previously outlined with respect to the first aspect also apply to the method for drying capsules according to the second aspect of the present disclosure. In particular, one advantage of the method for drying capsules of the second aspect is that it ensures a high degree of flowability of the assembly of capsules obtained. A further advantage is that the method operates under mild conditions, notably avoiding any mechanical and/or thermal stress, thus minimizing damages to the capsules during drying. In particular, the structural integrity of the capsules is at least largely, preferably fully, maintained during the drying process and leakage is minimized. Furthermore, the drying process also ensures high stability of the capsules in the assembly of capsules obtained.

In typical embodiments, any additional drying steps, in particular spray drying or freeze drying is avoided, i.e. the method is devoid of such additional drying steps.

In an embodiment, the wet raw composition comprises a further solvent, which is preferably miscible with water, such as for example DMF, acetone, acetonitrile, acetic acid, ethanol, methanol, propanol. In an embodiment, the ratio of the further solvent and the water is preferably such that the liquid core of the capsules is essentially insoluble in and essentially immiscible with the further solvent and the water. In an embodiment, the wet raw composition consists of water and the plurality of capsules. It is understood that the wet raw composition may still include trace amounts of other components, for example resulting from the method of manufacturing the wet raw composition. Preferably, these other components do not exceed 5 wt-%, preferably 2% wt-%, more preferably 1 wt-%, of the wet raw composition.

In an embodiment, the step of removing at least a portion of the drying agent comprises sieving. The sieve may have a mesh size of less than 1500 micrometer, preferably from 200 micrometer to 1100 micrometer. Sieving, particularly using the indicated mesh sizes, allows obtaining a high degree of flowability of the assembly of capsules. The used sieves typically have a mesh size which is smaller than the particle size of each capsule. As an example, the used sieves may have a mesh size which is smaller than the average particle size of the capsules or smaller than the particle size of the largest 95% capsules. Other methods may be used for removing at least a portion of the drying agent. As an example, in an embodiment, the step of removing at least a portion of the drying agent comprises one or more of the following: sifting, particularly windsifting, cyclonic separation.

In an embodiment, the wet raw composition is treated with the drying composition at less than 45 °C, preferably from 20 °C to 35 °C, more preferably 30 °C. Typically, the step of treating the wet raw composition is performed at a temperature above room temperature, i.e. above 23 °C. One advantage of these embodiments is that they minimize temperature- related damages to the capsules, such as structural damage to or structural disintegration of the matrix shell of the capsules, leakage of the capsules, among others.

In an embodiment, in the step of treating the wet raw composition with the drying composition, the ratio by weight of wet raw composition to drying agent is from 5 to 12, preferably from 6 to 10, more preferably 10. As an example, if the ratio by weight of wet raw composition to drying agent is 10, the weight of wet raw composition is ten times as big as the weight of the drying agent. In an embodiment, the ratio by weight of wet raw composition to drying composition is from 0.5 to 1.2, preferably from 0.6 to 1 , more preferably 1. One advantage of these embodiments is that they strike an advantageous balance between employing sufficient drying agent to ensure effective drying an, as a result, a high degree of flowability, on the one hand, and minimizing the amount of drying agent in the assembly of capsules eventually obtained as product on the other hand. Furthermore, these embodiments also contribute to high capsule stability.

In an embodiment, the step of treating the wet raw composition with the drying composition comprises mixing the wet raw composition and the drying composition to obtain a mixture and drying the mixture by heating, in particular in an oven, until the water content of the mixture is less than 50 wt-%. In an embodiment, the mixture is dried by heating until the water content of the mixture is less than 30 wt-%, preferably less than 20 wt-%, more preferably less than 10 wt-%, more preferably less than 5 wt-%, more preferably less than 2 wt-%, more preferably less than 1 wt-%, more preferably less than 0.5 wt-%, more preferably less than 0.1 wt-%. It is understood that, as outlined previously for the residual water content, the water content of the mixture refers to free water molecules in the mixture and does not include water molecules that are bound, e.g. coordinately, to the drying agent. As an example, residual water does not include the one, respectively six, water molecules present in CaCOs’ W and/or CaCO3*6H ₂ O. One advantage of these embodiments is that they ensure a high degree of flowability.

Preferably, the wet raw composition and the drying composition are mixed to obtain a homogenous mixture. Homogeneous, in this context, means that the capsules and the drying agent are uniformly distributed throughout the mixture. As an example, the homogeneous mixture may a suspension of the capsules and the drying agent in water, wherein the capsules and the drying agent are uniformly distributed throughout the water. These embodiments are advantageous because they ensure a high drying efficiency and result in a high degree of flowability.

In an embodiment, the mixture of the wet raw composition and the drying composition is stirred at less than 600 rpm, preferably less than 500 rpm, more preferably from 100 rpm to 400 rpm. These embodiments minimize damage to the capsules during the drying process, in particular, damage to the matrix shell. However, these rotation speeds were still found to be sufficient to ensure good mixing and a sufficiently high drying efficiency. In an embodiments, the stirring is performed using a magnetic stirrer. The indicated rotation speeds preferably relate to volumes of approximately 100 mL.

In an embodiment, the wet raw composition has a water content from 35 wt-% to 60 wt-%.

In an embodiment, the step of treating the wet raw composition with the drying composition may further comprise treating the mixture of the wet raw composition and the drying composition in a fluidized bed dryer. In an embodiment, the step of treating the wet raw composition with the drying composition comprises application of a subatmospheric pressure, such as less than 900 mbar, preferably less than 600 mbar, more preferably less than 250 mbar, more preferably less than 100 mbar. In an embodiment, the step of treating the wet raw composition with the drying composition is the only drying step applied. In an embodiment, the step of treating the wet raw composition with the drying composition does not comprise any one of the following: spray-drying or freeze-drying. These embodiments ensure mild drying conditions and thus minimize structural and/or functional damage to the capsules.

In an embodiment, the drying composition is a solution or suspension of the drying agent in a solvent such as water, DMF, acetonitrile, methanol or ethanol. Preferably, the solvent is water. Preferably, the drying composition is a 4 wt-% to 20 wt-% suspension in water, more preferably a 5 wt-% to 10 wt-% suspension in water. As an example, the drying composition may be a 4 wt-% to 20 wt-%, preferably a 5 wt-% to 10 wt-%, suspension of CaCCh in water. One advantage of these embodiments is that a suspension of a drying agent in a solvent, e.g. a suspension of CaCOs in water, is easy to handle. Surprisingly, using a suspension of a drying agent in water, such as a suspension of CaCOs in water, still allows for an efficient drying process even though water is added as part of the drying composition. These embodiments also ensure that the drying process proceeds in a smooth and gentle fashion, minimizing mechanical stress, which may lead to breakage of the capsules. A further advantage of these embodiments is that they minimize the amount of surface oil on the capsules in the assembly of capsules obtained.

In an embodiment, the drying composition is a 6 wt-% to 8 wt-%, particularly a 6 wt-%, suspension of a drying agent in water, preferably of CaCOs in water. It was found that, surprisingly, these concentrations lead to a minimum amount of surface oil in the assembly of capsules.

In an embodiment, the drying agent comprises an inorganic drying agent, such as CaCCh, silica, MgSC Na2SC>4, KOH, CaO CaCh, CaSO4, molecular sieves, preferably CaCOs, CaSO4 or silica, more preferably CaCOs. In an embodiment, the drying agent is an inorganic drying agent, such as CaCOs, silica, MgSO4, Na2SO4, KOH, CaO CaCh, CaSO4, molecular sieves, preferably CaCOs, CaSO4 or silica, more preferably CaCOs. In a preferred embodiment, the drying agent is water-insoluble, which means that the solubility in water is less than 1 g/L, preferably less than 0.2 g/L, more preferably less than 50 mg/L at 25 °C. In preferred embodiments, the drying agent is selected from CaCOs, CaSO4, silica and/or a stearate salt. In some embodiments, the drying agent is selected from CaCCh, CaSC>4 and silica, preferably CaCCh. These drying agents enable efficient drying of the capsules. They also allow a high degree of flowability to be achieved.

In an embodiment, the assembly of capsules obtained in the method of drying has an angle of repose of less than 45°, preferably less than 42°, more preferably from 34° to 41°.

In an embodiment, each capsule in the assembly of capsules obtained in step c. has a diameter of less than 3000 micrometers, particularly from 1 micrometer to 1000 micrometers, more particularly from 50 micrometers to 1000 micrometers, more particularly from 50 micrometers to 700 micrometers, more particularly from 50 micrometers to 500 micrometers. These embodiments ensure a high degree of flowability and stability. In an embodiment, the coefficient of variation with respect to the distribution of diameters of the capsules in the assembly of capsules obtained in step c. is less than 10%, particularly from 1 % to 8%.

In an embodiment, the thickness of the each matrix shell in the assembly of capsules obtained is less than 200 micrometers, particularly less than 130 micrometers, more particularly from 40 micrometers to 110 micrometers.

In an embodiment, the capsules in the assembly of capsules obtained have a sphericity index from 0.7 to 1 , particularly from 0.8 to 0.98. In an embodiment, the weight of surface oil on the capsules in the assembly of capsules obtained is less than 5 wt% relative to the weight of the capsules, particularly from 0.01 wt% to 3 wt%. In an embodiment, the assembly of capsules obtained has a residual water content of less than 5 wt-%, preferably less than 3 wt-%, more preferably less than 1 wt-%.

In an embodiment, the matrix shell comprises a polyelectrolyte, in particular a gelled polyelectrolyte, as disclosed hereinbefore, in particular with respect to the first aspect. In an embodiment, the steps of treating the wet raw composition with the drying composition and, optionally, removing at least a portion of the drying agent are performed such that the capsules shrink in diameter from 5% to 50%, particularly from 15% to 35%. This shrinkage in diameter refers to the shrinkage of the diameter of a capsule. It was found that these ranges lead to a high degree of capsule stability and a high degree of flowability.

In an embodiment, the step of providing the wet raw composition comprising water and a plurality of capsules comprises any of the embodiments disclosed in the patent application “Encased Oil Core Microcapsules”, PCT/EP2021/081705 (WO 2022/106361 A1) filed on 15 November 2021 , whose disclosure is incorporated into the present application by reference in its entirety. Particularly Figure 1 and the description of Figure 1 of PCT/EP2021/081705 is included by reference. In particular, in an embodiment, the step of providing the wet raw composition comprising water and a plurality of capsules comprises the “method for generating capsules with a matrix shell encasing an oil core” described in the patent application “Encased Oil Core Microcapsules”, PCT/EP2021/081705, in particular in the claims, e.g. the independent claims. In these embodiments, the core of each capsule is an oil core.

In an embodiment, the step of providing the wet raw composition comprising water and a plurality of capsules comprises the following steps: a. Providing in a first chamber a core-forming emulsion of an aqueous dispersed phase in an oil phase, the aqueous dispersed phase comprising water and a gelation-inducing agent, the emulsion further comprising a first surfactant; b. Providing in a second chamber a second aqueous solution, the aqueous solution comprising water and a second surfactant.

The first chamber and the second chamber are fluidic connected by one or more channels, preferably by micro-channels. The method further comprises the steps c. Guiding the core-forming emulsion of step a. from the first chamber through the one or more channels into the second chamber to form a dispersion of the coreforming emulsion of step a. in the second aqueous solution of step b.; d. Mixing the dispersion formed in step c. with an aqueous shell-forming solution, the aqueous shell-forming solution comprising water and a water soluble matrixforming agent.

The gelation-inducing agent and the matrix-forming agent are configured such that they are capable of undergoing a chemical reaction with each other to form a water insoluble matrix shell. The method further comprises the step e. Reacting the gelation-inducing agent and the matrix-forming agent in the dispersion formed in step c. to form capsules of a water insoluble matrix shell encasing an oil core.

It is understood that steps a. and b. must not necessarily be performed in this order. It may also be possible to first perform step b. and then step a. or perform them simultaneously.

It is understood that the dispersion formed in step c. comprises a plurality of monodisperse droplets comprising core-forming emulsion of step a. within the second aqueous solution as the continuous phase.

It is further understood that the formed oil core being encased by the water insoluble matrix shell may contain minor amounts of residual aqueous dispersed phase, i.e. minor amounts of water. However, the majority of the core is composed of the oil phase. Typically, more than 60 wt%, particularly more than 70 wt%, particularly more than 80 wt%, particularly more than 90 wt%, particularly more than 95 wt%, particularly more than 99 wt%.

Furthermore, the core-forming emulsion is not the emulsion forming as such the core of the final capsule, but also delivers reagents which react and/or diffuse from the core. Thus the core forming-emulsion in step a. is not necessarily fully identical, in particularly not with respect to its composition to the oil core of the final product.

In some embodiments, the gelation-inducing agent is dissolved in the water of the aqueous dispersed phase of step a. The advantage of a dissolved gelation-inducing agent is that clogging of the channels is avoided. Particularly carbonates may lead to accumulation of insoluble salts within the channels.

The core forming emulsion provided in step a. may be stable for 60 min to 600 min, preferably from 100 min to 500 min. Such a stability ensures that the droplets are not directly destroyed, particularly during step c. However, the droplet stability is also not too high which would decrease the efficiency of shell formation, i.e. step e.

The matrix-forming agent in step d. is typically dissolved in the aqueous shell-forming solution.

The gelation-inducing agent and the matrix-forming agent are configured such that they are capable of undergoing a chemical reaction with each other to form a water insoluble matrix shell. These may for example be configured to undergo a complexation reaction, an ionexchange reaction or an interphase limited polymerization reaction.

The first chamber and second chamber are typically separated from each other with the exception of the one or more channels connecting the first chamber with the second chamber. A chamber as used herein is configured for being filled with a solution. Typically, the chambers are closed with the exception of inlets, channels and outlets.

The first chamber has typically a first fluid inlet for introducing, particularly continuously introducing, the core-forming emulsion in step a. into the first chamber and the second chamber has a second inlet for introducing, particularly continuously introducing, the second aqueous solution into the second chamber in step b. The second chamber also has a dispersion outlet for removing, preferably continuously removing, the dispersion formed during step c. from the second chamber.

It is understood that the one or more channels each comprise an inlet opening into the first chamber and an outlet opening into the second chamber. Thus, the one or more channels are directly connected to the first chamber and the second chamber. Typically, the first chamber and the second chamber are fluidic connected by multiple channels, i.e. at least 10, at least 20, at least 30, at least 50 or at least 100 channels. Preferably, the first chamber and the second chamber are fluidic connected by 1 to 10 000 000, preferably 20 to 500 000 channels. Typically, the channels are arranged essentially parallel to each other.

For example, the one or more channels may have a diameter in the range of 0.25 to 2000 pm, preferably 2 to 800 pm. The multiple channels of the membrane are typically microchannels. For example, each channel may have a cross-sectional area of 0.04 pm ² to 4000 000 pm ² , preferably 4 pm ² to 640 000 pm ² .

In further embodiments, the aspect ratio of each channel, which is defined as channel length/minimum diameter, 5 to 1000, particularly, 10 to 500, more particularly 10 to 50. In some embodiments, the length of the channel may be in the range of 0.05 mm to 20 mm, particularly between 0.1 mm to 20 mm, particularly 0.1 mm to 5 mm, particularly 0.5 to 20 mm.

In certain embodiments each channel comprises a channel outlet with a cross-sectional area which is larger than the cross-sectional area of the remaining part of the respective channel. In the longitudinal direction, i.e. in the direction of flow, the channel outlet has a typical length of several micrometers, for example 200 pm to 20 mm, preferably 500 pm to 5 mm. The channel outlet may for example be funnel shaped, V-shaped or U-shaped. In some embodiments, the channel outlet may have an elliptical contour. In particular, the channel outlet is not rotational symmetric, thus having a ratio of length/width of 3 and higher. Hence, the channel outlet may not have a circular or square shaped cross-section. Such a channel outlet enables the detachment of a droplet without external force. As a result, droplet formation of the core-forming emulsion in the second aqueous solution is decoupled and thus essentially independent from the flow rate. According to the Young-Laplace equation, the pressure at an immiscible liquid interface is higher at the channel outlets than in the second reservoir. Thus a pressure gradient along the direction of the flow is generated, which causes the detachment of the fluid thread into individual droplets. Thus a pressure gradient is generated at the end of the channel, which facilitates the detachment of the fluids boundary layer and thus the formation of the individual droplets. When reaching the channel outlet, the pressure gradient of the disperse phase in and outside of the channel a droplet detaches without external force. Such a nozzle is advantageous, as it decouples the flow rates from the emulsification process.

Typically, each channel is defined by channel walls. The channel walls may be curved, i.e. the channel walls may be convexly or concavely shaped towards the channel outlet. Furthermore, each channel may comprise a constriction with a cross-section which is smaller than the cross-section of the rest of the channel and wherein the constriction is arranged adjacent the channel outlet. Thus, the constriction is arranged between the channel outlet and the rest of the channel.

In further embodiments, the cross-sectional area of each channel outlet is 0.12 to 36 000 000 pm ² , preferably 12 to 5 760 000 pm ² . In particular, total open area of the second side of the membrane may be 300% to 1500%, preferably 400% to 900%, larger than total open area of the channels at any other given position, such as the main section and/or the channel inlets.

In some embodiments, the one or more channels may be comprised in a membrane separating the first chamber from the second chamber. In such embodiments, the membrane can be flat, for example disc-shaped. The membrane typically has a first side facing the first chamber and a second side, being opposite to the first side and facing the second chamber. Thus, the first side of the membrane may partially limit the first chamber and the second side of the membrane may partially limit the second chamber. The one or more channels, typically multiple channels, extend from the first side to the second side through the membrane. Each channel comprises a channel inlet arranged at the first side, a channel outlet arranged at the second side and a main section being arranged between the channel inlet and channel outlet, wherein the channel outlet comprises a shape deviating from the shape of the main section.

The membrane may typically be a monolayer membrane. That is, the membrane is made from a single piece. Preferably, such a membrane is made from a massive material and does not contain any phase interfaces or transition areas in addition to the multiple channels of the membrane. Such a membrane is advantageous for the quality of the generated droplets, as any phase interfaces and transitions are detrimental to droplet formation and droplet stability.

In some embodiments, the membrane may be exchangeable. The multiple channels of the membrane are typically micro-channels. For example, each channel may have a cross- sectional area of 0.04 pm ² to 4 000 000 pm ² , preferably 4 pm ² to 640 000 pm ² .

In further embodiments, the channel outlet may be wedge-shaped. In particular, the channel outlet may comprise an elliptical cross-section with respect to a transversal plane being perpendicular to the extending channel, i.e. the channel outlet may be larger in a first direction than in a second direction.

In further embodiments, the second side of the membrane comprises a total open area that is larger than the total open area of the first side. Such a membrane has the advantage that high quality droplets are generated, even at flow rates of up to 5 I /h. In some embodiments, the flow rate per channel may be between 1 pl/h to 50 ml/h, preferably 10 pL/h to 5 ml/h.

In certain embodiments, each channel outlet may have an elliptical contour. Thus, the channel outlet may have an elliptical cross-section with respect to a plane being transversal to the extending channel and being parallel to the first or second side of the membrane. Channel outlets with an elliptical contour have a beneficial effect on the quality of the formed droplets, as any edges within the channel may lead to unstable and inhomogeneous droplets.

In some embodiments, the membrane is disk-shaped. Such a membrane may have a circular contour. Alternatively, the membrane may have an angular, particularly a triangular or rectangular, contour.

In further embodiments, the membrane comprises 0.06 to 600000 channels/cm ² , preferably 20 to 30 000 channels/cm ² .

In some embodiments, the membrane is made of glass or a polymeric material, such as polymethyl(meth)acrylate or PTFE or of a metallic material, such as steel.

In some embodiments, the oil phase in step a. additionally comprises at least one compound of interest. The compound of interested may be selected from a protein, small molecule particularly a fragrant or flavor, active pharmaceutical ingredient such as cannabinoids, hemp extracts, caffeine, melatonin or hyaluronic acid; antibody, peptide, enzyme, RNA, DNA, vitamin and micro-organisms. The compound of interest may for example be mixed into the oil phase in a suitable concentration.

In some embodiments, step a. comprises dissolving the gelation-inducing agent in water to form a solution and mixing the formed solution with the oil phase and with the first surfactant. The at least one compound of interest may in these embodiments be already mixed into the oil phase or also added only after the formed solution of the gelation-inducing agent in water is mixed with the oil phase. In some embodiments, mixing the formed solution of the gelation-inducing agent in water with the oil phase and the first surfactant comprises stirring with a stirrer at least 8 000 rpm, preferably at between 10 000 rpm to 20 000 rpm, e.g. at between 13 000 rpm and 15 000 rpm.

In specific embodiments, the at least one compound of interest in the core-forming emulsion, in particular in the oil phase or in the aqueous dispersed phase, is a living organism, in particular a microorganism, such as bacterium, a virus, including a phage, or a single cell. In some embodiments, the living organism may be provided in a dormant state into the core-forming emulsion, in particular in the oil phase or in the aqueous dispersed phase. It is understood that the dormant state of a living organism relates to an inactive state.

The method according to the invention is particular suitable for encapsulating living organisms, because the method exerts only marginal shear forces as compared to the method of the prior art. Furthermore, the encapsulation efficiency is significantly higher than of methods known in the prior art. It is possible to reach encapsulation efficiencies of up to 90% or even up to 95% with respect to the living organism.

In some embodiments, the method is performed at room temperature, which is highly beneficial for encapsulating living organisms, as the viability is increased.

In some embodiments, the core-forming emulsion, in particular in the oil phase or in the aqueous dispersed phase, additionally comprises nutritional components for the living microorganism, such as sugars, electrolyte solutions, and the like.

In certain embodiments, the core-forming emulsion, in particular in the oil phase or in the aqueous dispersed phase, additionally comprises buffer solutions configured to maintain a pH suitable for the corresponding living organism.

In some embodiments, the first surfactant is a nonionic surfactant, such as polyglycerol polyricinoleate (PGPR) or Span derivatives, such as Span 80 or Span 85 or a combination thereof. Furthermore, the first surfactant may be a solid particle, depending on the application preferably a hydrophobic hydrophilic or Janus-type particle, configured for providing a pickering emulsion. For example, the solid particle may be colloidal silica.

Preferably the first surfactant, particularly the non-ionic surfactant, has a molecular weight of between 600 and 120 000 g/mol, preferably between 800 and 80 000 g/mol. In some embodiments, the amount of first surfactant in the core-forming emulsion is between 0.01 wt% and 0.80 wt%, preferably between 0.05 wt% and 0.12 wt%.

In some embodiments, the amount of the second surfactant in the second aqueous solution is between 0.5 wt% and 5 wt%, in particular 1 wt% to 2 wt%.

5 In some embodiments, the second surfactant has a molecular weight of between 600 and 120 000 g/mol, preferably between 800 and 80 000 g/mol.

Typically, the first surfactant and the second surfactant are different and thus not identical.

In some embodiments, the second surfactant is selected from polyvinylalcohol (PVA), a polysorbate, such as Tween 20 or Tween 80, saponins, sapogenins, i.e. quillaja extract, gum Arabic, beta lactoglobulin, sodium dodecyl sulfate, soy lecithin, sodium caesinate, potato protein isolate (for example Solanic 300, Avebe®), whey protein isolate, starch octenyl succinate or a combination thereof. Preferably from polyvinylalcohol, a polysorbate, such as Tween 20 or Tween 80, beta lactoglobulin and starch octenyl succinate. With polyvinylalcohol, a polysorbate, such as Tween 20 or Tween 80, beta lactoglobulin and5 starch octenyl succinate a relatively thick and stable shell as compared to other second surfactants has been obtained. Polyvinylalcohol additionally provided an excellent monodispersity of the droplets of the core-forming emulsion in the second aqueous solution. Furthermore, the second surfactant may be a solid particle, depending on the application preferably a hydrophobic hydrophilic or Janus-type particle, configured for providing a0 pickering emulsion. For example, the solid particle may be colloidal silica. If PVA shall be avoided, gum arabic, Tween 20, potato protein, pectin or mixtures thereof may be employed as second surfactant, respectively as PVA replacement. Particular suitable examples include the use of 1 wt% - 5wt%, particularly 2 wt% to 4 wt%, of gum Arabic (for example Agri-Spray Acacia RE, Agrigum®) together with 0.25 wt% to 4 wt%, particularly 1 wt% to 25 wt%, of Tween 20 as the second surfactant in the second aqueous solution; or 0.5 wt% to 5 wt%, particularly 1 wt% to 3 wt%, of potato protein isolate (for example Solanic 300, Avebe®) as the second surfactant in the second aqueous solution; or 0.5 wt% to 5 wt%, particularly 0.5 wt% to 2 wt%, of pectin (for example sugar beet pectin: Swiss Beta Pectin, Schweizer Zucker AG®) together with 0.25 wt% to 4 wt%, particularly 1 wt% to 2 wt%, of Tween 20 as the second surfactant in the second aqueous solution. With these examples as second surfactant, a size distribution with a coefficient of variation of below 10% is readily possible. In some embodiments in which potato protein isolate is employed as the second surfactant, the pH of the second aqueous solution is adjusted to pH 9-11 , preferably to pH 10.

In some embodiments, the matrix-forming agent is a polyelectrolyte, particularly a polysaccharide or suitable salt thereof. A suitable salt is a salt form which can be completely dissolved in water. Typically, polysaccharide salts are composed of an anionic polysaccharide component and a suitable counter cation. Suitable polysaccharides are selected from chitosan, cellulose, alginate, particularly sodium alginate, carrageenan, agar, agarose, pectins, gellan, starch, and the like. Preferred polysaccharides are alginate, preferably sodium alginate, chitosan, carrageenan and cellulose, more preferably alginate, preferably sodium alginate, chitosan. In some embodiments, the polysaccharides may be solubilized by adjusting the pH, for example by basifying the pH of the aqueous shellforming solution.

In some embodiments, the matrix-forming agent and the gelation-inducing agent are selected such that the formed water insoluble matrix breaks and/or melts at a temperature of at least 80°C, in particular of at least 90 °C. Such embodiments, have the advantage that a compound of interest within the capsules is released at a specific, predetermined temperature. This is for example of particular interest for capsules being used as food additives. Such capsules may be completely odorless when they are intact, but break when they are cooked, such that the odor of interest is only liberated during cooking. In certain embodiments, the gelation inducing agent may be an alkaline earth metal salt, particularly a calcium salt such as CaCh, or an alkaline metal salt, such as KCI, and the matrix forming agent may be carrageenan, or a mixture of carrageenan and sodium alginate, preferably in a ratio of 2:1 to 1 :2. Alternatively agar-agar, optionally combined with sodium alginate, may be used as matrix forming agent in such embodiments. Preferably, 0.25 wt% to 2 wt%, in particular 0.5 wt% to 1.5 wt of carrageenan are used in the aqueous shell-forming solution. For example, if 1.5 wt% of carrageenan in water is used in step d. as the aqueous shellforming solution, capsules are formed which start to melt at 80 °C. If on the other hand, 0.75 wt% carrageenan together with 0.5 wt% sodium alginate in water is used in step d. as the aqueous shell-forming solution, then capsules are formed which are more stable and break open at around 80 °C, but do not yet melt completely.

Alternatively, the matrix-forming agent may be a polycarboxylate. In this case, the gelation inducing agent may be an inorganic salt as describe above which can form a water insoluble matrix upon ion exchange with the polycarboxylate. Alternatively, the gelation-inducing agent may be a polyammonium salts, i.e. a polymer comprising a plurality of polyammonium groups.

As an alternative, the matrix-forming agent may be a monomer being soluble in the water phase but not in the oil. Such a monomer must be selected such that it can undergo a stepgrowth polymerization, for example a diamine. In this case the gelation-inducing agent is a monomer being soluble in the oil phase but not in water, such as a diacid chloride, thereby enabling an interface polymerization during step e for forming the water insoluble matrix.

In some embodiments, the amount of matrix-forming agent in the aqueous shell-forming solution is between 0.1 wt-% to 2 wt-%, preferably between 0.5 wt-% to 1.0 wt%.

In some embodiments, a third surfactant, for example a Polysorbate, such as Tween 20 may be present in or added to the aqueous shell-forming solution prior to step d. It has been found that such a third surfactant improves the gelation reaction.

In some embodiments, the gelation-inducing agent is an inorganic salt, particularly an alkaline earth metal salt, particularly an alkaline earth metal halide, an alkaline earth metal pseudohalide, an alkaline earth metal carboxylate or an alkaline earth metal nitrate, or an alkaline metal halide, an alkaline metal pseudohalide, an alkaline metal carboxylate or an alkaline metal nitrate. In some embodiments in which the gelation-inducing agent is an inorganic salt, as outlined above, the reaction in step e. between the gelation-inducing agent and the matrix-forming agent is an ion exchange reaction, i.e. an ionotropic gelation. Thus, the inorganic salt (and vice versa the matrix-forming agent) are selected such that its reaction with the matrix-forming agent results in a water insoluble reaction product. Particularly suitable salts, especially for polysaccharides, may thus be K, Mg, Sr or Ca salts. The skilled person understands the term “pseudohalide”, which is also referred to as “pseudohalogenide” as polyatomic analogues of halogens, whose chemistry resembles that of true halogens. Non-limiting examples include cyanide, isocyanide, cyanate, isocyanate, methylsulfonyl and triflyl. Non limiting examples of carboxylates are acetate, formate, lactate, oxalate, butyrate, succinate and the like. The gelation-inducing agent is typically selected such that it is completely soluble in water at room temperature, i.e. has a solubility in water of >10g/100mL, preferably of > 20g/100mL, particularly of >50g/100mL. Nonlimiting examples of suitable gelation-inducing agents are: CaCI ₂ , CaF2, Calcium lactate, MgCI ₂ , Sr(OAc) ₂ .

The inorganic salt is typically a water soluble salt. However, it also conceivable to employ a powder of a water insoluble salt as gelation-inducing agent. For example, it may be possible to employ CaCCh or MgCOa, particularly as a powder.

In some embodiments, the gelation-inducing agent is a composition of a photoacid generator, i.e. a compound being configured to produce an acid upon irradiation, preferably UV irradiation, such as diphenlyiodonium nitrate, and chelate of an inorganic salt, particularly an alkaline earth metal salt or an alkaline metal salt. The chelate may for example be a chelate of a carboxylic acid. A suitable example may be a chelate of strontium an ethylene glycol tetraacetic acid. Upon irradiation with UV light, which may be performed in step e., the photoacid generator generates an acid, which then liberates the strontium ions, which in turn react with the matrix-forming agent, for example with sodium alginate to form a water insoluble matric shell. In some embodiments, the gelation-inducing agent is CO2 or a CO2 generator. A CO2 generator can liberate CO2 under specific conditions. For example, bicarbonate may liberate CO2 in the presence of an acid.

In some embodiments, the gelation inducing agent may be a Bronsted acid, for example a mineral acid or a carboxylic acid. In this case, the matrix-forming agent may be a composition of a polysaccharide, such as an alginate, chitosan, etc. and a suitable water soluble alkaline metal complex or alkaline earth metal complex, such as Ca-Na2-EDTA, Mg- Na ₂ -EDTA, Sr-Na ₂ -EDTA and the like.

In some embodiments, the amount of the gelation-inducing agent in the core-forming emulsion is between 1 .5 wt-% - 7.0 wt-%, preferably between 2.0 wt-% to 5.0 wt-%.

In some embodiments, an alcohol, particularly methanol, ethanol or propanol, is added to the aqueous shell-forming solution prior to step d. It has been found that the alcohol enhances the diffusion of the gelation-inducing agent towards the interface of the microdroplets. The alcohol is typically present in an amount of 10 to 30 wt% of the aqueous shell-forming solution. It has been observed that of the alcohol amount is between 10 to 20 wt%, preferably at 13 to 17 wt%, the core size of the capsule, i.e. the core diameter, is larger than if more ethanol is used. For example, a microcapsule diameter of larger than 300 pm can be achieved. If the amount of alcohol is between 20 to 30 wt%, preferably at 23 to 27 wt%, (under otherwise identical conditions) the core size of the capsule, i.e. the core diameter, is smaller. For example, a microcapsule diameter of less than 300 pm can be achieved.

In some embodiments, a structural stabilizer may be added to or being present in the aqueous shell-forming solution prior to step d. A structural stabilizer are compounds configured for enhancing the structural stability of the shell. Examples include agarose as well as xanthan gum or cellulose and derivatives, for example methylcellulose or microcrystalline cellulose, and the like. These may typically be present in the shell-forming solution which are then integrated into the growing shell during step e. In some embodiments, the aqueous shell-forming solution of step d. comprises in addition to the matrix-forming agent, an additional biopolymer as structural stabilizer, such as pectin (for example GENU® pectin type LM-104 AS-FG). Preferably, the additional biopolymer may also be able to form a matrix shell.

In certain embodiments, the additional biopolymer may be solid biopolymer particles, e.g. starch. Providing such an additional biopolymer and in particular solid biopolymer particles increases the mechanical strength of the generated capsules.

In some embodiments, the concentration of the additional biopolymer, and in particular of the solid biopolymer particles in the aqueous shell-forming solution is from 1 wt-% to 30 wt- %, particularly from 3 wt-% to 20 wt-%. In some embodiments, the concentration of the additional biopolymer is from 1 wt-% to 10 wt-%. In some embodiments, the concentration of the additional biopolymer is from 5 wt-% to 10 wt-%. Particular suitable solid particles are starch particles, such as corn starch particles or potato starch particles. Further examples of solid particles include dextrin, such as dextrin from corn. The ranges provided in this paragraph refer to the weight of the solid biopolymer relative to the weight of the aqueous shell-forming solution.

In some embodiments, the particle size of the solid particles is equal or less than 100 pm, particularly equal or less than 50 pm, more particularly equal or less than 20 pm, more particularly equal or less than 15 pm.

In some embodiments, the one or more channels have a channel diameter from 50 micrometer to 150 micrometer, preferably from 80 micrometer to 120 micrometer, more preferably 100 micrometer. In some embodiments, the one or more channels have a channel diameter of 400 micrometer to 600 micrometer, preferably 470 micrometer to 530 micrometer, more preferably 500 micrometer. In some embodiments, the one or more channels have a cross-sectional area from 5’000 square micrometer to 10’700 square micrometer, preferably from 6’850 square micrometer to 8’850 square micrometer, more preferably 7’850 square micrometer. In some embodiments, the one or more channels have a cross-sectional area from 120’000 square micrometer to 280’000 square micrometer, preferably from 170’000 to 230’000 square micrometer, more preferably 196’350 square micrometer. One advantage of these embodiments is that the assembly of capsules obtained display very little surface oil.

5 Brief description of the figures

The herein described invention will be more fully understood from the detailed description given herein below and the accompanying drawings which should not be considered limiting to the invention described in the appended claims. The drawings are showing:

Fig. 1 A schematic representation of the method according to the disclosure; 0 Fig. 2 shows microscopic images of an assembly of capsules according to the present disclosure;

Fig. 3 shows the amount of surface oil measured for assemblies of capsules that were dried at 30 °C and 50 °C;

Fig. 4 shows the amount of surface oil measured for assemblies of capsules that were dried using aqueous CaCOs suspensions of different concentrations;

Fig. 5 shows a microscopic image and the size distribution of an assembly of capsules according to the present disclosure;

Fig. 6 shows the amount of surface oil measured for assemblies of capsules that were manufactured using channels with different diameters. 0 Exemplary embodiments

Figure 1 illustrates schematically the method according to an embodiment of the present disclosure. In a first step (S1 ) a wet raw composition is provided which consists of a plurality of microcapsules 1 and water. In the illustrated embodiment, the microcapsules are calcium alginate capsules having an oil core. In the illustrated embodiment, the microcapsules have been manufactured using 1 wt-% Na-alginate. In the illustrated embodiment, the shell of the alginate capsules comprises no fillers. The wet raw composition is arranged inside a container 2 which, in the illustrated embodiment, is cylindrical with a height of 5.5 cm and a diameter of 9 cm. In the illustrated embodiment, the raw composition has a weight of 80 g. In a second step (S2), a 10 wt-% suspension of CaCOs 4 in water is added to the raw composition and the resulting mixture 3 is stirred. Before addition, the CaCOs suspension 4 in water was shaken or stirred vigorously to ensure a homogeneous distribution of CaCOs. The amount of CaCOs suspension 4 added is 80 g, thus giving a ratio of capsules to CaCOs suspension of 1 :1. In a third step (S3), the mixture obtained in step S2 is dried in an oven 5 at 30 °C until total water evaporation. In the illustrated embodiment, the mixture was dried in the oven 5 at 30 °C for 3 days before it was sieved in a fourth step (S4) using a 1 mm 1355 micrometer sieve to remove excess CaCOs to obtain an assembly of capsules 6 which has a high degree of flowability. The assembly of capsules 6 comprises 5.6% CaCOs relative to the weight of dried capsules.

Figure 2a shows a microscopic image of an assembly of capsules according to the present disclosure. The assembly of capsules was manufactured using the method disclosed herein using channels with a channel diameter of 200 micrometers. Figure 2b shows a zoomed-in section of the image of figure 2a. The images illustrate the spherical shape of the capsules. The images were taken with a different type of lightning.

Figure 3 shows the amount of surface oil measured for an assembly of capsules that were dried according to the present disclosure. The capsules were manufactured using, as shell-forming solution, 1 wt-% Na-alginate and using channels with a channel diameter of 200 micrometer. The capsules are blank, i.e. they do not contain an active ingredient encased in the matrix shell. The amount of surface oil is indicated as weight percent relative to the weight of the dried capsules. The amount of surface oil was determined by shaking a mixture of 2 g of the assembly of capsules with 15 mL of hexane in a vortex mixer, followed by filtration through a filter paper (grade 602h with a pore size of less than 2 micrometer). After rinsing the filtrand three times with 20 mL of hexane, the filtrate solution is left to evaporate at 23 °C and 1 bar and then dried at 60 °C and 1 bar until constant weight was obtained. The resulting constant weight corresponds to the weight of surface oil. As illustrated, the amount of surface oil is 1.78% for an assembly of capsules dried in an oven at 30 °C, while it is 2.90% for an assembly of capsules manufactured under the same conditions except that it was dried in an oven at 50 °C.

Figure 4 shows the amount of surface oil measured for an assembly of capsules that were dried and manufactured under the same conditions outlined for figure 3 above, except that the capsules were all dried in an oven at 30 °C and that a suspension of CaCOs in water of varying concentration was used, namely 10 wt-% (left bar), 7 wt-% (middle bar) and 5 wt-% (right bar). Surprisingly, the amount of surface oil, once again indicated as weight percent relative to the weight of dried capsules, is 2.17% when using a 10 wt-% CaCOs suspension, 0.75% when using a 7 wt-% CaCOs suspension, and 0.87% when using a 5 wt-% CaCOs suspension.

Figure 5a shows a microscopic image of an assembly of capsules according to the present disclosure that was manufactured as described above for figure 3, except that the capsules were dried in an oven at 30 °C and that the capsules are filled with beta-carotene. Figure 5b shows the size distribution of the assembly shown in figure 5a. The graph shows the total size distribution of the capsules, i.e. twice the shell thickness and the oil core diameter. The average particle size of the capsules is 532.1 micrometer with a coefficient of variation of 3.7%.

Figure 6 shows the amount of surface oil measured for assemblies of capsules that were manufactured using channels with different diameters. All samples were manufactured under the same conditions outlined for figure 3, except that the capsules were dried in an oven at 30 °C and that channels with different diameters were used. All but the first sample were manufactured using 1 % Na-alginate (AL). All samples contain beta-carotene (BC) in the core. Surprisingly, it was found that the amount of surface oil, as weight percent relative to the weight of the dried capsules, is particularly low when using channels with channel diameters of 100 micrometer or 500 micrometer compared to 200 micrometer.