Soft capsule shell and preparation method thereof

Abstract

The invention provides a soft capsule shell, which is prepared from the following raw materials in parts by weight: 10 to 20 parts of modified gelling agent, 40 to 80 parts of modified starch, 2 to 6 parts of thickening agent, 1 to 4 parts of antioxidant, 25 to 40 parts of plasticizer and 80 to 120 parts of deionized water. The modified gelling agent is prepared from seaweed gel, microbial gum and edible gum in a mass ratio of 1: (1.3-1.6): (2-3). The seaweed gel is agar or carrageenan; the microbial gum is gellan gum or xanthan gum; the edible gum is pectin or konjac gum; the prepared soft capsule shell has good tensile strength, elongation at break and other properties, and has good enteric solubility.

Description

Technical Field

[0001] The invention relates to the technical field of soft capsule preparation, and in particular to a soft capsule shell and a preparation method thereof. Background Art

[0002] Soft capsules are a type of capsule packaging, commonly found in medicines or health foods. They are a type of capsule made by sealing the treated liquid drug in a capsule shell material. Traditional enteric soft capsules are mainly coated, first producing soft capsules and then coating them to obtain an enteric effect. In recent years, research has mainly used one-step molding to prepare enteric soft capsules, that is, adding enteric materials during the sol process, pressing pills, and finally drying. It uses a non-coated form that does not require a separate coating. This type of non-coated enteric soft capsule can improve the storage durability of coated soft capsules. Compared with the traditional preparation process, its process is simplified, efficiency is improved, and cost is reduced.

[0003] Patent CN106456558A proposes to prepare soft capsules with gelatin and low methoxyl pectin, but the enteric solubility of the soft capsules deteriorates after the reaction between monovalent and divalent cations and pectin, and the enteric solubility of the soft capsules is further deteriorated after long-term storage, and gelatin is easy to cross-link due to aging or reaction with compounds such as aldehydes. Although it tolerates acid in artificial gastric juice, it cannot break and disintegrate in intestinal juice. Patent CN106473093A proposes a fish skin gelatin chewable soft capsule and a preparation method thereof, comprising: fish skin gelatin, glycerin, gelling agent (gellan gum, carrageenan or gum arabic), sugar alcohol, modified starch and sodium hydroxymethyl cellulose. The rubber skin made of such a mixture still has good chewability after being placed for a period of time, and will not become hard and difficult to chew, but the rubber skin contains more gelatin, and the filler is liquid or suspended oil, and the greasy feeling is obvious when chewing. The existing soft capsule shell is easy to pre-gel in the process, resulting in a rough and uneven surface, lack of strength and toughness, and poor enteric solubility. Summary of the invention

[0004] The purpose of the present invention is to provide a soft capsule shell and a preparation method thereof, which improves the performance index of the soft capsule shell and has a good enteric solubility effect by taking a modified gelling agent and modified starch as the main component and supplementing with other effective ingredients.

[0005] In order to achieve the above object, the present invention provides the following technical solutions: A soft capsule shell, the raw materials of which include the following components in parts by weight: 10-20 parts of a modified gelling agent, 40-80 parts of a modified starch, 2-6 parts of a thickener, 1-4 parts of an antioxidant, 25-40 parts of a plasticizer and 80-120 parts of deionized water.

[0006] Furthermore, the modified gelling agent is composed of alginate, microbial glue and edible glue in a mass ratio of 1:1.3-1.6:2-3.

[0007] Furthermore, the seaweed gum is agar or carrageenan; the microbial gum is gellan gum or xanthan gum; and the edible gum is pectin or konjac gum.

[0008] Furthermore, the modified starch is obtained by subjecting a mixture of hydroxypropyl starch, hydroxypropyl distarch phosphate and acetylated oxidized starch in a mass ratio of 1:2-3:2-5 to microwave and enzymatic hydrolysis treatment.

[0009] Furthermore, the thickener is pullulan or sodium alginate; the antioxidant is dodecyl gallate or butylated hydroxyanisole; and the plasticizer is glycerol, sorbitol or mannitol.

[0010] Furthermore, the soft capsule shell component also includes 3-8 parts of calcium acetylacetonate.

[0011] The method for preparing the soft capsule shell comprises the following steps: S1: sequentially preparing a modified gelling agent and a modified starch; S2: Mix 10-20 parts of modified gelling agent, 40-80 parts of modified starch and 80-120 parts of deionized water, and stir and react at a temperature of 85-105° C. for 45-75 minutes; S3: Add 3-8 parts of calcium acetylacetonate to step S2, and continue stirring for 15-25 minutes; then add 2-6 parts of thickener, 1-4 parts of antioxidant and 25-40 parts of plasticizer, stir and react at a temperature of 55-75°C for 1-3 hours, and remove bubbles to obtain a glue solution; S4: The glue liquid in step S3 is pelletized, shaped, and dried until the moisture content of the glue skin is 15-25%, thereby obtaining the soft capsule shell.

[0012] Furthermore, the preparation process of the modified gelling agent in step S1 is: mixing alginate, microbial gum and edible gum in a mass ratio of 1:1.3-1.6:2-3, and stirring the mixture at a temperature of 100-120°C for 2-4 hours.

[0013] Furthermore, the preparation process of the modified starch in step S1 is: mixing hydroxypropyl starch, hydroxypropyl distarch phosphate and acetylated oxidized starch in a mass ratio of 1:2-3:2-5, treating at a power of 800-1000 for 1-3 minutes, adding 0.5-1.5% by weight of α-amylase, and performing enzymatic hydrolysis for 20-40 minutes to obtain modified starch.

[0014] Furthermore, the parameters for pilling in step S3 are: the temperature of the pilling syringe is 85-95°C, the temperature of the glue solution is 80-95°C, the temperature of the spreading box is 80-95°C, the cold air temperature is 40-45°C; the mold speed is 2-4r / min; the rubber thickness is 0.7-0.9mm.

[0015] Compared with the prior art, the advantages and beneficial effects of the present invention are: The present invention uses seaweed gel, microbial gel and edible gel to form a gelling agent, and the gelling agent is made by compounding the three; modified hydroxypropyl starch, hydroxypropyl distarch phosphate and acetylated oxidized starch mixture are used as modified starch; the network structure formed by cross-linking each other is used to improve the strength and toughness of the capsule shell, ensure that it does not break in gastric juice, breaks in intestinal juice, and has a good enteric effect; under the further action of calcium acetylacetonate, the gap adhesion is good; under the conditions of thickener, plasticizer, antioxidant, etc., the comprehensive performance of the soft capsule shell is further improved. The soft capsule shell prepared by the present invention has a disintegration time limit of more than 2 hours in gastric juice and disintegrates within 10-20 minutes in colonic fluid, which meets the provisions of the national pharmacopoeia. DETAILED DESCRIPTION

[0016] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0017] The raw materials used in the present invention are as follows: Agar was from Qingdao Dehui Marine Biotechnology Co., Ltd., item number 082101; gellan gum was from CP Kelco, item number SK30008627; carrageenan was from CP Kelco, item number 119945; xanthan gum was from Jiangsu Weizhirun Biotechnology Co., Ltd., item number 3335; pectin was from Jiangsu Weizhirun Biotechnology Co., Ltd., item number S11082; konjac gum was from Shanghai Yuanye Biotechnology Co., Ltd., item number S30903; hydroxypropyl starch was from Hunan Erkang Pharmaceutical Co., Ltd., item number R20221107; hydroxypropyl distarch phosphate was from Arena (Shanghai) Trading Co., Ltd., item number 4302003; acetylated oxidized starch was from Xi'an Ruixi Biotechnology Co., Ltd., item number 5142; pullulan was from Shanghai Yuanye Biotechnology Co., Ltd., item number S11198; glycerin was from Shanghai Fandi Oil Technology Co., Ltd., item number 1245.

[0018] Example 1 This embodiment provides a method for preparing a soft capsule shell, comprising the following steps: S1: agar, gellan gum and pectin in a mass ratio of 1:1.3:2 were mixed, and stirred at a temperature of 100°C and a speed of 500 r / min for 2 h to obtain a modified gelling agent; Hydroxypropyl starch, hydroxypropyl distarch phosphate and acetylated oxidized starch in a mass ratio of 1:2:2 were mixed, treated at a power of 800 W for 1 min, 0.5% by mass of α-amylase was added, and the enzymatic reaction was carried out for 20 min to obtain modified starch; S2: 10 g of modified gelling agent, 40 g of modified starch and 80 g of deionized water were mixed, and stirred at 85°C and 550 r / min for 45 min; S3: Add 3g of calcium acetylacetonate to step S2, and continue stirring at a rate of 550r / min for 15min; then add 2g of pullulan, 1g of dodecyl gallate and 25g of glycerol, stir at a temperature of 55°C and a rate of 500r / min for 1h, and remove bubbles to obtain a glue solution; S4: Pressing and shaping the glue liquid described in step S3, the temperature of the pill pressing syringe is 85°C, the glue liquid insulation temperature is 80°C, the spreading box temperature is 80°C, and the cold air temperature is 40°C; the mold speed is 2r / min, and the rubber thickness is 0.7mm; drying at a temperature of 80°C until the moisture content of the rubber is 15%, thereby obtaining the soft capsule shell.

[0019] Example 2 This embodiment provides a method for preparing a soft capsule shell, comprising the following steps: S1: Carrageenan, xanthan gum and konjac gum are mixed in a mass ratio of 1:1.6:3, and stirred at a temperature of 120°C and a speed of 500 r / min for 4 hours to obtain a modified gelling agent; Hydroxypropyl starch, hydroxypropyl distarch phosphate and acetylated oxidized starch in a mass ratio of 1:3:5 were mixed, treated at a power of 1000 W for 3 minutes, 1.5% by mass of α-amylase was added, and the enzymatic reaction was carried out for 40 minutes to obtain modified starch; S2: 20 g of modified gelling agent, 80 g of modified starch and 120 g of deionized water were mixed, and stirred at 105°C and 550 r / min for 75 min; S3: Add 8g of calcium acetylacetonate to step S2, and continue stirring at a rate of 550r / min for 25min; then add 6g of sodium alginate, 4g of butylated hydroxyanisole and 40g of sorbitol, stir at a temperature of 75°C and a rate of 500r / min for 3h, and remove bubbles to obtain a glue solution; S4: Pressing and shaping the glue liquid described in step S3, the temperature of the pill pressing syringe is 95°C, the glue liquid insulation temperature is 95°C, the spreading box temperature is 95°C, and the cold air temperature is 45°C; the mold speed is 4r / min, the rubber thickness is 0.9mm; drying at a temperature of 80°C until the water content of the rubber is 25%, thereby obtaining the soft capsule shell.

[0020] Example 3 This embodiment provides a method for preparing a soft capsule shell, comprising the following steps: S1: Agar, gellan gum and konjac gum in a mass ratio of 1:1.5:2.5 were mixed, and the mixture was stirred at a temperature of 110°C and a speed of 500 r / min for 3.5 h to obtain a modified gelling agent; Hydroxypropyl starch, hydroxypropyl distarch phosphate and acetylated oxidized starch in a mass ratio of 1:2.5:4 were mixed, treated at a power of 950 W for 2 minutes, 1.2% by mass of α-amylase was added, and the enzymatic reaction was carried out for 35 minutes to obtain modified starch; S2: 16 g of modified gelling agent, 65 g of modified starch and 110 g of deionized water were mixed, and stirred at 95 °C and 550 r / min for 65 min; S3: Add 6 g of calcium acetylacetonate to step S2, and continue stirring at a rate of 550 r / min for 22 min; then add 4 g of pullulan, 3 g of butylated hydroxyanisole and 35 g of glycerol, stir at a temperature of 65° C. and a rate of 500 r / min for 2.5 h, and remove bubbles to obtain a glue solution; S4: Pressing and shaping the glue liquid described in step S3, the temperature of the pill pressing syringe is 90°C, the glue liquid insulation temperature is 90°C, the spreading box temperature is 92°C, and the cold air temperature is 42°C; the mold speed is 3r / min, the rubber thickness is 0.8mm; drying at a temperature of 85°C until the water content of the rubber is 22%, thereby obtaining the soft capsule shell.

[0021] Comparative Example 1 The difference between this comparative example and Example 1 is that only seaweed glue is included in step S1, and microbial glue and edible glue are missing, and the other steps are the same.

[0022] Comparative Example 2 The difference between this comparative example and Example 1 is that in step S1, only microbial glue is present, and seaweed glue and edible glue are absent, and the other steps are the same.

[0023] Comparative Example 3 The difference between this comparative example and Example 1 is that in step S1, only edible glue is present, and seaweed glue and microbial glue are absent, and the other steps are the same.

[0024] Comparative Example 4 The difference between this comparative example and Example 1 is that in step S2, the starch mixture is not modified, that is, hydroxypropyl starch, hydroxypropyl distarch phosphate and acetylated oxidized starch are mixed in a mass ratio of 1:2:2 and treated at a power of 800 W for 1 min, and the other steps are the same.

[0025] Comparative Example 5 The difference between this comparative example and Example 1 is that calcium acetylacetonate is missing in step S3, and the other steps are the same.

[0026] Performance Test: The tensile properties and dissolution time of the capsule shells obtained in each embodiment and comparative example were tested. Among them, the test method of tensile properties: prepare a dumbbell-shaped film sample with a length of 20 mm, a width of 4 mm, and a thickness of about 0.1 mm, and use a physical property tester (TA.XT PLUSC of SMS Company, UK) to test the tensile properties at a tensile speed of 10 mm / min. The test method of disintegration time: prepare an artificial colon fluid containing β-mannanase, and the artificial colon fluid is prepared as follows: take 6.8 g of dipotassium hydrogen phosphate, adjust the pH to 6.8 with sodium hydroxide solution, take 10 g of β-mannanase, add an aqueous solution, mix the two solutions, and dilute with water to 1000 ml. Take 0.5 g of soft capsules of each formula and place them in a disintegrator to measure their disintegration time. The results are as shown in the following table: Table 1

[0027] From the above performance test results, it can be seen that Examples 1-3 have excellent performance in tensile strength and elongation at break, and the disintegration time meets the requirements. In particular, the comprehensive performance of Example 3 is the most outstanding. However, since Comparative Examples 1-5 do not adopt the necessary technical solutions, their corresponding performance tests are significantly worse than those of the Examples. The above experimental results further prove the importance of the technical solutions defined in the present invention for its technical effects.

[0028] The above is a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A soft capsule shell, characterized in that: The raw materials include the following components in parts by weight: 10-20 parts of modified gelling agent, 40-80 parts of modified starch, 2-6 parts of thickener, 1-4 parts of antioxidant, 25-40 parts of plasticizer and 80-120 parts of deionized water.

2. A soft capsule shell according to claim 1, characterized in that: The modified gelling agent consists of alginate, microbial glue and edible glue in a mass ratio of 1:1.3-1.6:2-3.

3. A soft capsule shell according to claim 2, characterized in that: The seaweed gum is agar or carrageenan; the microbial gum is gellan gum or xanthan gum; and the edible gum is pectin or konjac gum.

4. A soft capsule shell according to claim 1, characterized in that: The modified starch is obtained by subjecting a mixture of hydroxypropyl starch, hydroxypropyl distarch phosphate and acetylated oxidized starch in a mass ratio of 1:2-3:2-5 to microwave and enzymatic hydrolysis treatment.

5. A soft capsule shell according to claim 1, characterized in that: The thickener is pullulan or sodium alginate; the antioxidant is dodecyl gallate or butylated hydroxyanisole; and the plasticizer is glycerol, sorbitol or mannitol.

6. A soft capsule shell according to claim 1, characterized in that: Also included is 3-8 parts of calcium acetylacetonate.

7. A method for preparing a soft capsule shell, characterized in that: The steps include: S1: preparing a modified gelling agent and a modified starch in sequence; S2: 10-20 parts of modified gelling agent, 40-80 parts of modified starch and 80-120 parts of deionized water are mixed, and stirred at a temperature of 85-105° C. for 45-75 minutes; S3: Add 3-8 parts of calcium acetylacetonate to step S2, and continue stirring for 15-25 minutes; then add 2-6 parts of thickener, 1-4 parts of antioxidant and 25-40 parts of plasticizer, stir and react at a temperature of 55-75°C for 1-3 hours, and remove bubbles to obtain a glue solution; S4: The glue liquid in step S3 is pelletized, shaped, and dried until the moisture content of the glue skin is 15-25%, thereby obtaining the soft capsule shell.

8. The method for preparing a soft capsule shell according to claim 7, characterized in that: The preparation process of the modified gelling agent in step S1 is: mixing alginate, microbial gum and edible gum in a mass ratio of 1:1.3-1.6:2-3, and stirring and reacting at a temperature of 100-120°C for 2-4 hours.

9. The method for preparing a soft capsule shell according to claim 7, characterized in that: The preparation process of the modified starch in step S1 is as follows: hydroxypropyl starch, hydroxypropyl distarch phosphate and acetylated oxidized starch in a mass ratio of 1:2-3:2-5 are mixed, treated at a power of 800-1000 for 1-3 minutes, 0.5-1.5% by mass of α-amylase is added, and the enzymatic reaction is carried out for 20-40 minutes to obtain the modified starch.

10. The method for preparing a soft capsule shell according to claim 7, characterized in that: The parameters for pilling in step S3 are: the temperature of the pilling syringe is 85-95°C, the temperature of the glue solution is 80-95°C, the temperature of the spreading box is 80-95°C, the cold air temperature is 40-45°C; the mold speed is 2-4r / min; the rubber thickness is 0.7-0.9mm.

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