Technical Field

The invention relates to obtaining thebaine from thebaine-rich poppy capsule by using the method of alcohol extraction.

State of the Art

Thebaine (paramorphine), also known as codeine methyl enol ether, is an opium alkaloid originating from Thebai (Thebes), an ancient city in Egypt. Thebaine, a minor component of opium, is chemically similar to both Morphine and Codeine, but has stimulant rather than depressant effects. In high doses, it causes convulsions similar to strychnine poisoning. The synthetic enantiomer (+) - Thebaine, unlike the inactive natural enantiomer (-) - Thebaine, exerts analgesic effects through opioid receptors. Although not used for therapeutic purposes, the Thebaine is the main alkaloid extracted from Papaver Bracteatum and can be industrially converted into various compounds such as hydrocodone, hydromorphone, oxycodone, oxymorphone, nalbuphine, naloxone, naltrexone, buprenorphine, and etorphine. Butorphanol can also be derived from Thebaine.

EXTRACTION TRIALS FOR OBTAINING RAW THEBAINE

A-) Extraction Trials with Water:

Extraction trials were carried out in 5 different environments with water by grinding the thebaine-rich capsule. These experiments were carried out with Lime, Acetic Acid, Caustic, Formic Acid solutions and in medium which contains water only. Before starting the experiments, the results of capsule analysis were checked. You can find below the results of analysis of capsules which were requested from warehouse to be rich in thebaine. Thebaine-rich poppy capsules ground with a grinding mill with 5 or 6 mm sieves were mixed with a mechanical mixer for 1 hour in an aqueous medium at 40 <0 and at 5 different pH levels. Extraction contents were filtered through centrifuge cloth. The analysis results of extracts and cakes obtained in the filtration process are given in the table below.

Although the solid-liquid yields for Thebaine were not very high in the extraction experiments performed in aqueous environments, liquid-liquid extraction and precipitation studies were continued with extracts to obtain Raw Thebaine. However, separation of organic phase and aqueous phase with thebaine extracts obtained from aqueous media was not possible due to the high rate of emulsions. Therefore, in the thebaine extraction studies, the aqueous phase extraction was abandoned and 80% ethanol extraction method was used. B-) Extraction Trials with Alcohol:

The same capsule, which was tested with water, was tested in 80% Ethanol medium and by using 3 different chemicals. After stirring for 1 hour at 40C, extract and cake analyzes were performed by filtration.

Analysis results are listed in the table below.

According to the results of different Thebaine extraction studies performed in alcohol and aqueous medium, it was observed that the extraction with Ethanol was more successful than the aqueous medium reactions. It is seen in the table above that the type of base used in the ethanol extraction method has no significant contribution to the extraction efficiency. However, due to its widespread use, it was decided to be the base to be used in the NaOH extraction method.

In the analyzes made during the extraction studies, it was observed that there are two different types of thebaine-rich capsules. The first is a thebain-rich species that contains only half as much morphine and other alkaloids as thebaine, and the second one is a species that contains less amount of alkaloids except Thebaine and Oripavine. The chromatograms of these two types of capsules obtained by HPLC are given below.

Tipi : Tip2:

When results of analyzes made with these two different capsules are compared to each other, it is observed that Type 2 contains approximately 1 .8% of Thebaine, while Type 1 contains 0.8-1 .2% of Thebaine. In addition, the rate of morphine is much higher in Type 1 compared to Type 2. Differences in both the structure and alkaloid content of these two types of poppy capsules create differences in the thebaine production process. Type 2 brittle Thebaine-rich poppy capsule with higher Thebaine and less foreign alkaloid content should be chosen as the raw material for the planned Thebaine production line in the future. If the Type 1 capsule with thicker and more woody structure and relatively low thebaine content is used in the process, lower yields, phase separation problems and problems in the precipitation processes will be experienced. In addition, if a poppy strain is developed that contains only Thebaine and Oripavine without Morphine, this method will allow to isolate Thebaine and Oripavine alkaloids separately from a single poppy capsule.

Obtaining raw thebaine by alcohol extraction:

To achieve the invention;

• Thebain-rich poppy capsule is grinded in a sieve and made into particles suitable for extraction,

• Solid-liquid phase is realized with alcohol extraction,

• Extraction is made with Toluene-Butanol

• HCI Solution extraction is made

• Thebaine is preciptated.

First of all, Thebain-rich poppy capsule is grinded in a sieve and made into particles suitable for extraction.

After that, following steps should be applied: • A certain weight of capsules or the extract obtained at the end of the processes is mixed with an aqueous solution of 80% ethanol; During extraction, 35% NaOH is added to keep the pH level at 9; The extract obtained at the end of filtration is mixed with activated carbon and diatomaceous soil and it is filtered; The obtained clear alcohol extract is subjected to vacuum distillation to remove the ethanol;

• The resulting extract is removed;

• After filtration, cake is obtained;

• 80% ethanol solution as much as the removed extract is added to the cake obtained from the filtration process and it is mixed; For pH=9 level, 35% NaOH solution is added and it is filtered;

• After filtration, the cake is discarded;

• The extract obtained at the end of the processes is subjected to the above processes at least 4 more times;

• Removed extracts are taken into a beaker and their pH is brought to 4 with concentrated HCI;

• Obtained main extract with pH=4 is filtered once again to obtain an aqueous extract at the end of the processes;

• Then, at pH=4 level, the main extract is mixed with 35% NaOH (Caustic) and pH is brought to 12,25;

• Extracts are divided into two parts,

• After both extracts are mixed with Toluene-Butanol mixture with pH 12 extract, they are kept in a separating funnel for phase separation and after the phases are separated from each other, the water phase is taken into a beaker for the second extraction;

• pH of both aqueous phases (extracts) is brought back to 12 by adding caustic solution and mixed by adding Toluene-Butanol mixture on the aqueous phase, and after the phases are separated from each other, the water phase is taken into the beaker for the third extraction;

• pH of both aqueous phases (extracts) is brought back to 12 by adding caustic solution and mixed by adding Toluene-Butanol mixture on the aqueous phase, and after the phases are separated from each other, the water phase is taken into the beaker for the third extraction;

• Thebaine is transferred to the organic phase at the end of 3 extractions;

• Toluene-Butanol phase is extracted in 3 steps with 1% HCI solution;

• 1% HCI solution is prepared;

• The Toluene-Butanol phase is mixed with the HCI solution, and finally the contents of the beaker are taken into the separating funnel, when the phase separation occurs, the aqueous phase and the organic phases are separated from each other;

• Remaining Toluene-Butanol phase is mixed with the HCI solution, and finally the contents of the beaker are taken into the separating funnel, when the phase separation occurs, the aqueous phase and the organic phases are separated from each other;

• Remaining Toluene-Butanol phase is mixed with the HCI solution, and finally the contents of the beaker are taken into the separating funnel, when the phase separation occurs, the aqueous phase and the organic phases are separated from each other;

• The HCI phases obtained as a result of the three extraction processes are combined;

• The total acid phase obtained is heated and the pH of the medium is brought to the range of 9.4-9.6 by adding 35% NaOH to the acid phase;

• The contents of the beaker are mixed at ambient temperature;

After the mixing process is completed, the filtering process is performed and the wet cake obtained is dried to obtain Dry Raw Thebaine;

Obtaining the aqueous extract can also be roughly summarized as follows:

1A:

• The capsule of a certain weight is mixed with an aqueous solution of 80% ethanol at 50 <0 for 1 hour;

• During extraction, 35% NaOH is added to keep the pH level at 9;

• The 1 st extract obtained at the end of coarse filtration is mixed with activated carbon and diatomaceous soil and filtered through fimasel;

• The obtained clear alcohol extract is subjected to vacuum distillation to remove the ethanol;

The 1 st extract and 1 A cake are obtained as result of above process steps.

2B:

• An aqueous solution of 80% ethanol obtained as result of filtration of 1 st extract is added to the cake obtained by filtration of 1 A and mixed;

• For pH=9 level, 35% NaOH solution is added and after filtration, 2B cake is thrown and 2B extract is taken to 2 A,

2A:

• The extract from 2B is made up for with 80% alcohol and mixed with the thebaine-rich poppy capsule;

• During extraction, 35% NaOH is added to keep the pH level at 9;

• The 2nd extract obtained at the end of coarse filtration is mixed with activated carbon and diatomaceous soil and filtered

• The obtained clear alcohol extract is subjected to vacuum distillation to remove ethanol; 3B:

• An aqueous solution of 80% ethanol, whose amount is equal to that of the 2nd extract, is added to the cake obtained from the filtration of 2A and mixed under the same conditions,

• 35% NaOH is added to achieve pH=9;

• After filtration, the 3B cake is discarded and the 3B extract is taken to 3A.

3A:

• The extract from 3B is made up for with 80% alcohol and mixed with the thebaine-rich poppy capsule;

• During extraction, 35% NaOH is added to keep the pH level at 9;

• The 3rd extract obtained at the end of coarse filtration is mixed with activated carbon and diatomaceous soil and filtered

• The obtained clear alcohol extract is subjected to vacuum distillation to remove ethanol;

4B:

• An aqueous solution of 80% ethanol, whose amount is equal to that of 3rd extract, is added to the cake obtained from the filtration of 3A and mixed under the same conditions,

• About 5 ml of 35% NaOH is added to achieve pH=9 and it is filtered;

• After filtration, the 4B cake is discarded, the 4B extract is taken to 4A.

4A:

• The extract from 4B is made up for with 80% alcohol and mixed with the thebaine-rich poppy capsule;

• During extraction, 35% NaOH is added to keep the pH level at 9;

• The 4th extract obtained at the end of coarse filtration is mixed with activated carbon and diatomaceous soil and filtered

• The obtained clear alcohol extract is subjected to vacuum distillation to remove ethanol; 5B:

• An aqueous solution of 80% ethanol, whose amount is equal to that of 4th extract, is added to the cake obtained from the filtration of 4A and mixed under the same conditions,

• 35% NaOH is added to achieve pH=9 and is filtered;

• After filtration, the 5B cake is discarded, the 5B extract is taken to 5A.

5A:

• The extract from 5B is made up for with 80% alcohol and mixed with the thebaine-rich poppy capsule;

• During extraction, 35% NaOH is added to keep the pH level at 9;

• The 5th extract obtained at the end of coarse filtration is mixed with activated carbon and diatomaceous soil and filtered

• The obtained clear alcohol extract is subjected to vacuum distillation to remove ethanol;

6B:

• An aqueous solution of 80% ethanol, whose amount is equal to that of 5th extract, is added to the cake obtained from the filtration of 5A and mixed under the same conditions,

• 35% NaOH is added to achieve pH=9 and is filtered;

• After filtration, the 5B cake is discarded, the 5B extract is taken to 5A.

6A:

• The extract from 6B is made up for with 80% alcohol and mixed with the thebaine-rich poppy capsule;

• During extraction, 35% NaOH is added to keep the pH level at 9;

• The 5th extract obtained at the end of coarse filtration is mixed with activated carbon and diatomaceous soil and filtered

• The obtained clear alcohol extract is subjected to vacuum distillation to remove ethanol; Removed extracts are taken into a beaker and their pH is brought to 4 with concentrated HCI;

The obtained main extract with pH=4 main is filtered one more time through fimasel.

The invention was explained with the above steps. In order to keep the scope of protection wide, it is explained in above steps by removing the measurements, temperatures and time periods. However, below is given the summary of an experiment we have implemented, together with all the measurements, time periods and temperatures, so that the reader can see the results and understand the subject better.

OBTAINING RAW THEBAINE BY ALCOHOL EXTRACTION

A-) Solid-Liquid Extraction

Thebain-rich poppy capsule was grinded by means of a 6 mm sieve into particles suitable for extraction. 750 g of thebaine-rich grinded poppy capsule was mixed with 6 liters of 80% Ethanol solution at pH=9 and 50 <0 by one hour to complete solid-liquid extraction. Solid-liquid extraction was done with the logic of a two-stage reverse flow system. In the solid-liquid experiments, it was observed that Thebaine content of the capsule containing approximately 1 .8% Thebaine decreased to 0.3-0.4% at the end of the first stage extraction, and to 0.1 % when it was subjected to the second stage extraction.

The flow chart and data of the method based on the two-stage reverse flow system determined for thebaine extraction are given below.

Flow Chart:

1 A: 750 g of capsule is mixed with 6 liters of aqueous solution of 80% ethanol at 50 <0 for 1 hour. During extraction, 40 ml of 35% NaOH is added to keep the pH level at 9. The 1 st extract obtained from coarse filtration is mixed with 10 g of activated carbon and 20 g of diatomaceous soil at 40C by 5 minutes and filtered through fimasel. The obtained clear alcohol extract is subjected to vacuum distillation to remove ethanol.

2B: An aqueous solution of 80% ethanol, whose amount is equal to that of 1 st extract is added to the cake obtained from filtration of 1 A and is mixed by 1 hour under same conditions. About 5 ml of 35% NaOH solution is added to bring pH level to 9. 2B cake is discarded after filtering. 2B extract is taken to 2A.

2A: Extract from 2B is made up to 6 liters by adding 80% of alcohol and is mixed with 750 g of thebaine-rich poppy capsule at 50 D by 1 hour. During extraction, 40 ml of 35% NaOH is added to keep the pH level at 9. The 2nd extract obtained from coarse filtration is mixed with 10 g of activated carbon and 20 g of diatomaceous soil at 40C by 5 minutes and filtered through fimasel. The obtained clear alcohol extract is subjected to vacuum distillation to remove ethanol.

3B: An aqueous solution of 80% ethanol, whose amount is equal to that of 2nd extract is added to the cake obtained from filtration of 2A and is mixed by 1 hour under same conditions. About 5 ml of 35% NaOH solution is added to bring pH level to 9. 3B cake is discarded after filtering. 3B extract is taken to 3A.

3A: Extract from 3B is made up to 6 liters by adding 80% of alcohol and is mixed with 750 g of thebaine-rich poppy capsule at 50 O by 1 hour. During extraction, 40 ml of 35% NaOH is added to keep the pH level at 9. The 3rd extract obtained at the end of coarse filtration is mixed with 10 g of activated carbon and 20 g of diatomaceous soil at 40C by 5 minutes and filtered through fimasel. The obtained clear alcohol extract is subjected to vacuum distillation to remove ethanol.

4B: An aqueous solution of 80% ethanol, whose amount is equal to that of 3rd extract is added to the cake obtained from filtration of 3A and is mixed by 1 hour under same conditions. About 5 ml of 35% NaOH solution is added to bring pH level to 9. 4B cake is discarded after filtering. 4B extract is taken to 4A.

4A: Extract from 4B is made up to 6 liters by adding 80% of alcohol and is mixed with 750 g of thebaine-rich poppy capsule at 50 O by 1 hour. During extraction, 40 ml of 35% NaOH is added to keep the pH level at 9. The 4th extract obtained at the end of coarse filtration is mixed with 10 g of activated carbon and 20 g of diatomaceous soil at 40C by 5 minutes and filtered through fimasel. The obtained clear alcohol extract is subjected to vacuum distillation to remove ethanol.

5B: An aqueous solution of 80% ethanol, whose amount is equal to that of 4th extract is added to the cake obtained from filtration of 4A and is mixed by 1 hour under same conditions. About 5 ml of 35% NaOH solution is added to bring pH level to 9. 5B cake is discarded after filtering. 5B extract is taken to 5A.

5A: Extract from 5B is made up to 6 liters by adding 80% of alcohol and is mixed with 750 g of thebaine-rich poppy capsule at 50 D by 1 hour. During extraction, 40 ml of 35% NaOH is added to keep the pH level at 9. The 5th extract obtained from coarse filtration is mixed with 10 g of activated carbon and 20 g of diatomaceous soil at 40C by 5 minutes and filtered through fimasel. The obtained clear alcohol extract is subjected to vacuum distillation to remove ethanol.

6B: An aqueous solution of 80% ethanol, whose amount is equal to that of 5th extract is added to the cake obtained from filtration of 5A and is mixed by 1 hour under same conditions. About 5 ml of 35% NaOH solution is added to bring pH level to 9. 6B cake is discarded after filtering. 6B extract is taken to 6A.

6A: Extract from 6B is made up to 6 liters by adding 80% of alcohol and is mixed with 750 g of thebaine-rich poppy capsule at 50 O by 1 hour. During extraction, 40 ml of 35% NaOH is added to keep the pH level at 9. The 6th extract obtained from coarse filtration is mixed with 10 g of activated carbon and 20 g of diatomaceous soil at 40C by 5 minutes and filtered through fimasel. The obtained clear alcohol extract is subjected to vacuum distillation to remove ethanol.

Removed extracts are taken into a beaker and their pH is brought to 4 with concentrated HCL The obtained main extract with pH=4 main is filtered one more time through fimasel. About 8.500 ml of aqueous extract is obtained as result of these steps.

Flow Chart

SOLID-LIQUID extraction yields of thebaine studies made in this way were calculated based on the amount of thebaine remaining in the cake. Amounts of thebaine remaining in the cake after extraction:

It is seen from the table that the amount of thebaine remaining in discarded cakes is 0.11. According to this;

1 .684 - 0.1 = 1 .584 (The amount of thebaine in the extract)

Yield % 1,584/1,684x100= 94,06 %

It is predicted that this efficiency will be much higher if high capacity extractors are used in the production process.

B-) LIQUID-LIQUID EXTRACTION

Extraction with Toluene-Butanol: pH of 8500 ml main extract, which was 4 before the process, was brought to 12.25 by adding 135 ml of 35% NaOH (Caustic Acid). Extracts were divided into two parts, each was 4.25 liters, and following steps were applied to both of them: 4 liters of Toluene-Butanol mixture (75% Toluene - 25% Butanol) was prepared. 3 extractions were made with toluene to obtain 1700 ml of Toluene/Butanol mixture.

Extractions were made at 40 ^< C.

• Liquid-Liquid Extraction: 4.25 L extract with pH 12 is mixed with 800 ml Toluene- Butanol mixture at 40 <0 for 10 minutes and then le ft in a separatory funnel for 30 minutes for phase separation. After phases are separated from each other, the water phase is taken into beaker for the second extraction.

• The pH of aqueous phase (extract) is brought back to 12 by adding caustic solution. 500 ml Toluene-Butanol mixture is added to aqueous phase, mixed at 40C for 10 minutes, and then left in a separatory funnel for 30 minutes for phase separation. After phases are separated from each other, the aueous phase is taken into beaker for the third extraction.

• The pH of aqueous phase (extract) is brought back to 12 by adding caustic solution. 400 ml Toluene-Butanol mixture is added to aqueous phase, mixed at 40C for 10 minutes, and then left in a separatory funnel for 30 minutes for phase separation. Phases are separated from each other. Thebaine is transferred to the organic phase at the end of 3 extractions.

Aqueous phase analyzes of both 4.25 L of extracts at 3rd stage are given in the table below.

1. Liquid-Liquid Extraction Analysis Results for Aqueous Extract 2. Liquid-Liquid Extraction Analysis Results for Aqueous Extract

As a result of the 3 Toluene-Butanol extractions made to the pH 12 extract, it is seen that it passes into organic phase and is separated from other main alkaloids, Morphine and Oripavine.

Toluene-Butanol phases obtained at the end of liquid-liquid extraction of pH 12 extract are combined to obtain 3930 mL of organic phase.

HCI Solution extraction: 3930 mL of Toluene-Butanol phase is extracted in 3 stages with 3 L of 1 % HCI solution (v/v). 3 liters of 1 % HCI solution is prepared. pH of HCI solution is measured about 1.22.

1 -) Total Toluene-Butanol phase is mixed with 1600 ml of HCI solution at 40 <C for 10 minutes. At the end of the mixing process, the content of beaker is taken into separation funnel for phase separation. When phase separation occurs, the aqueous and organic phases are separated from each other. After phase separation, the pH of aqueous phase is measured about 5.45.

2-) 1000 ml of HCI solution is added to Toluene-Butanol phase, which remained after 1 st extraction, and it is mixed at 40 <C for 10 min utes. At the end of the mixing process, the content of beaker is taken into separation funnel for phase separation. When phase separation occurs, the aqueous and organic phases are separated from each other. After phase separation, the pH of aqueous phase is measured about 1 .82.

3-) 400 ml of HCI solution is added to Toluene-Butanol phase, which remained after 2nd extraction, and it is mixed at 40 <C for 10 min utes. At the end of the mixing process, the content of beaker is taken into separation funnel for phase separation. When phase separation occurs, the aqueous and organic phases are separated from each other. After phase separation, the pH of aqueous phase is measured about 1 .44.

HCI phases obtained from three extraction processes are combined;. Results of the analysis made with aqueous phases obtained from extraction processes are given in the table below.

3-) PRECIPITATING OF THEBAINE

The 1 st, 2nd and 3rd acid phases obtained from HCI extraction are combined and the total volume is measured about 4100 mL. The total acid phase obtained is heated and the heating process is terminated when the temperature reaches 40 ^< C. By adding 35% NaOH to the acid phase at 40 ^< C, the pH of the medium is brought to the range of 9.4-9.6 (pH=9.6 in this experiment). During pH adjustment process, it is observed that precipitation starts around pH=6 and continues until pH=8.7, and after this pH, the pH value of the environment increases rapidly with the addition of NaOH solution.

Therefore, after pH reaches 8.7, the addition of NaOH solution should be done in a controlled and slow manner. The contents of beaker are stirred at ambient temperature for approximately 16 hours. After the mixing process is completed, filtering is done and the weight of the wet cake is recorded about 121 .1 grams. The wet cake is dried in a fan oven at 55 <0 for approximately 4 hours. At the end of drying, approximately 66.4 grams of Dry Raw Thebaine is obtained.

In the end of Raw Thebaine Production Process R&D trials, trial products of Thebain 11 , Thebain 12 and Thebain 13 were produced and the analysis results of these studies are given in the tables below.

THEBAINE 11 ANALYSIS RESULTS

.4 L TOTAL EXTRACT

AFTER TOLUENE EXTRACTION OF 1ST PART AQUEOUS PHASE

AFTER HCL EXTRACTION OF 1ST PART HCI PHASE 4 L TOTAL EXTRACT

AFTER TOLUENE EXTRACTION OF 2ND PART AQUEOUS PHASE

AFTER HCL EXTRACTION OF 2ND PART HCI PHASE

Total HCI Phase Before Precipitating THEBAINE 12 ANALYSIS RESULTS THEBAINE 13 ANALYSIS RESULTS

EFFICIENCY CALCULATIONS OF PILOT SCALE TRIAL PRODUCTIONS

THEBAINE - 11

Thebaine amount in the capsule = 1 .684%

Amount of capsules entered with 4 steps of extraction = 5x750 gr = 3750 grams Amount of Thebaine = 3750 x 1 .684 / 100 = 63.15 grams

Since the 6th step is a single-stage extraction process, the remaining amount in the cake is not considered as a complete loss and the amount of Thebaine from single- stage extraction is accepted as an input to the process. 1.684-0.5 (Remaining in the Cake) = 1.184 x 750 gr / 100 = 8.88 grams

Total Thebaine Amount Input = 63.15 + 8.88 = 72.03 grams

Thebaine-11 Amount Obtained by Production = 58.1 Gram

Content as Result of Analysis = 98.195%

Total Thebaine Produced = 58,1x98,195 / 100 = 57,05 gram

EFFICIENCY = 57,05 / 72,03 x 100 = 79,2%

THEBAINE - 12

Thebaine amount in the capsule = 1 .832%

Amount of capsules entered with 5th step of extraction = 3.750 gr Amount of Thebaine = 3.750 x 1 .832 / 100 = 68,7 grams

Since the 6th step is a single-stage extraction process, the remaining amount in the cake is not considered as a complete loss and the amount of Thebaine from single- stage extraction is accepted as an input to the process.

1 .832-0.3(Remaining in the Cake) = 1.532 x 750 gr I 100 = 11.49 grams Total Thebaine Amount Input = 68.7 + 11 .49 = 80.19 grams

Amount of Thebaine-11 Obtained by Production = 66.4 grams

Content as Result of Analysis = 99,511%

Total Thebaine Produced = 66,4x99,511 1 100 = 66,07

Efficiency = 66,07/80,19 x 100 = 82,3%

TEBAIN - 13

Thebaine amount in the capsule = 1 ,832%

Amount of capsules entered with 5th step of extraction = 3.750 gr

Amount of Thebaine = 3.750 x 1 .832 / 100 = 68,7 grams Since the 6th step is a single-stage extraction process, the remaining amount in the cake is not considered as a complete loss and the amount of Thebaine from single- stage extraction is accepted as an input to the process.

1.832-0.6 (Remaining in the Cake) = 1 ,232 x 750 gr / 100 = 9,24 grams Total Thebaine Amount = 68,7+9,24 = 77,94 grams

Thebaine-11 Amount Obtained by Production = 69.8 Gram

Content as Result of Analysis = 97,673%

Total Thebaine Produced = 69,8x97,6731 100 = 68,17 gram

Efficiency = 68,17 / 77,94 x 100 = 87,46%