Hydroxypropyl starch empty capsule and preparation method thereof

Abstract

The invention relates to the technical field of capsules, in particular to a hydroxypropyl starch empty capsule and a preparation method thereof. The hydroxypropyl starch hollow capsule is prepared from the following raw materials in parts by weight: 5 to 20 parts by weight of hydroxypropyl starch, 0.1 to 0.6 part by weight of carrageenan, 0 to 0.1 part by weight of potassium chloride, 0 to 0.5 part by weight of pullulan, 0 to 0.3 part by weight of glycerol, 0 to 0.1 part by weight of nano titanium dioxide, 0 to 0.05 part by weight of pigment and 20 to 50 parts by weight of water. By adding the modified hydroxypropyl starch, the stability and solubility of the hydroxypropyl starch can be improved, so that the dissolution rate and stability of the capsule are improved, the solubility and bioavailability of the product are improved, the release and absorption of components in the capsule are facilitated, the disintegration rate is good, and the friability can be reduced.

Description

Technical Field

[0001] The invention relates to the technical field of capsules, and in particular to a hydroxypropyl starch hollow capsule and a preparation method thereof. Background Art

[0002] Hydroxypropyl starch hollow capsules are a new type of oral drug dosage form. They are composed of hydroxypropyl starch and other excipients. They are usually translucent hard shell capsules and are mainly used for oral drugs. With the increasing attention paid to food safety and animal product safety issues, the limitations of gelatin capsules have gradually emerged, such as being easily affected by acids and alkalis, being sensitive to environmental temperature and humidity, and possibly posing animal disease risks. Therefore, as an alternative, hydroxypropyl starch hollow capsules have attracted research and development attention due to their advantages such as wide material sources, high safety, excellent disintegration performance and friability.

[0003] In the process of preparing hydroxypropyl starch hollow capsules, key technologies include selecting suitable hydroxypropyl starch raw materials, adjusting the degree of substitution, optimizing the sol and drying processes, etc. The degree of substitution of hydroxypropyl starch has a significant effect on the performance of the capsule. Studies have shown that when the degree of substitution is 1.5%-4.6%, the prepared starch hollow capsules meet the requirements of the 2015 edition of the Pharmacopoeia of the People's Republic of China. When the degree of substitution is 2.3%, the performance of the hollow capsule is the best.

[0004] In addition, the preparation method of hydroxypropyl starch hollow capsules is also constantly innovating. For example, a preparation method of hydroxypropyl starch hollow capsules includes mixing hydroxypropyl starch, gelling agent, coagulant and water in proportion, stirring evenly, placing in a water bath at a set temperature to gelatinize the starch, then adding glycerol and nano-ultrafine calcium carbonate, stirring evenly to form a glue solution, standing to remove bubbles in the glue solution, and finally preparing capsule blanks through a fully automatic hollow capsule manufacturing machine and drying.

[0005] In terms of raw material selection, the preparation of hydroxypropyl starch hollow capsules uses starch as raw material, which is cheap and low-cost, and avoids the problem of environmental pollution caused by the discharge of sewage in the production of traditional gelatin products. This method of preparing capsules not only improves the quality and stability of the product, but also has environmental advantages. In summary, the research and development of hydroxypropyl starch hollow capsules aims to provide a new type of hollow capsule with superior performance, high safety, low cost and environmental protection to meet the needs of the pharmaceutical, food and health care products industries. With the continuous advancement and innovation of technology, hydroxypropyl starch hollow capsules are expected to become an important direction for the development of future pharmaceutical dosage forms. Summary of the invention

[0006] In view of the above-mentioned deficiencies in the prior art, the present invention provides a hydroxypropyl starch hollow capsule and a preparation method thereof.

[0007] In order to solve the above technical problems, the technical solution adopted by the present invention is: A hydroxypropyl starch hollow capsule is composed of the following raw materials in parts by weight: 5-20 parts by weight of hydroxypropyl starch, 0.1-0.6 parts by weight of carrageenan, 0-0.1 parts by weight of potassium chloride, 0-0.5 parts by weight of pullulan, 0-0.3 parts by weight of glycerol, 0-0.1 parts by weight of nano titanium dioxide, 0-0.05 parts by weight of pigment, and 20-50 parts by weight of water.

[0008] Preferably, the hydroxypropyl starch hollow capsules are composed of the following raw materials in parts by weight: 8-14 parts by weight of hydroxypropyl starch, 0.2-0.36 parts by weight of carrageenan, 0.01-0.05 parts by weight of potassium chloride, 0.01-0.27 parts by weight of pullulan, 0.01-0.12 parts by weight of glycerol, 0.005-0.05 parts by weight of nano titanium dioxide, 0.001-0.02 parts by weight of pigment, and 35-45 parts by weight of water.

[0009] More preferably, the hydroxypropyl starch hollow capsules are composed of the following raw materials in parts by weight: 10 parts by weight of pregelatinized hydroxypropyl starch or modified hydroxypropyl starch, 0.3 parts by weight of carrageenan, 0.02 parts by weight of potassium chloride, 0.15 parts by weight of pullulan, 0.1 parts by weight of glycerol, 0.03 parts by weight of nano-titanium dioxide, 0.01 parts by weight of pigment, and 40 parts by weight of water.

[0010] The hydroxypropyl starch is pregelatinized hydroxypropyl starch or modified hydroxypropyl starch.

[0011] The pigment is any one of synthetic pigment, natural pigment, plant pigment, red iron oxide and yellow iron oxide.

[0012] Unlike gelatin hollow capsules, hydroxypropyl starch hollow capsules are non-animal products, made with pregelatinized hydroxypropyl starch or modified hydroxypropyl starch as the main film-forming material. More than 90% of the ingredients of hydroxypropyl starch hollow capsules are pregelatinized hydroxypropyl starch. Therefore, its basic properties are mainly determined by the properties of hydroxypropyl starch. Hydroxypropyl starch is a soluble starch derivative. In terms of chemical structure, hydroxypropyl groups are introduced into the main chain of starch, which makes the starch molecules have better water solubility and viscosity reduction properties. It is also a relatively stable substance. Its solution properties are also stable, and it undergoes sol-gel transition during heating and cooling. Hydroxypropyl starch has excellent film-forming, dispersibility and adhesion, and is extremely compatible with most substances. Therefore, hydroxypropyl starch hollow capsules have no risk of cross-linking reaction, high chemical stability, and high water retention, which can effectively solve the problem of fragile capsules.

[0013] During the preparation of pregelatinized hydroxypropyl starch, the hydroxyl groups on the starch molecular chain react with propylene oxide to introduce hydroxypropoxy groups, which increase the hydrophilicity of the starch molecules and improve their water absorption and swelling properties. Part or all of the starch granules are destroyed by physical methods. This treatment makes the structure of the starch granules looser and can form a more uniform and tough capsule wall. This uniformity helps to improve the mechanical strength of the capsule and reduce the risk of breakage during storage and transportation. At the same time, it has better freeze-thaw stability and solubility in cold water, and improves its ability to absorb water and swell. This enhanced water absorption is conducive to the rapid disintegration of the capsule in the body and improves the release rate of the drug.

[0014] The preparation process of the pregelatinized hydroxypropyl starch comprises the following steps: N1: 15-25 parts by weight of starch is added to 60-90 parts by weight of water, and the mixture is stirred to obtain a starch emulsion. A swelling agent is added at a ratio of 2-6 wt% of the weight of the starch, and the mixture is heated at 80-100° C. for 1.5-2.5 h, cooled to room temperature, filtered, and washed to obtain a pre-swollen starch. N2: After mixing all the above pre-swollen starch, 60-90 parts by weight of water and 0.5-3 parts by weight of propylene oxide, adjust the pH to 11-12 with 1-3 mol / L sodium hydroxide aqueous solution, heat and react at 35-45°C for 10-24h, cool to room temperature, neutralize with 0.5-2 mol / L hydrochloric acid until the system is neutral, filter, wash, and dry to obtain hydroxypropyl starch; N3: Mix all of the above hydroxypropyl starch and 40-70 parts by weight of water, and stir at 70-85° C. and 300-600 rpm for 30-70 min to obtain pregelatinized hydroxypropyl starch.

[0015] As a modified starch, pregelatinized hydroxypropyl starch has many excellent properties, such as good disintegration, adhesion, solubility and freeze-thaw stability, which makes it widely used in medicine, food and other fields. However, in order to further expand its application range, improve performance or reduce costs, further modification is needed on the basis of pregelatinized hydroxypropyl starch.

[0016] The addition of lactic acid and carboxymethyl cellulose can improve the water absorption and swelling of hydroxypropyl starch, which helps the capsule to quickly absorb water and swell in the body, thereby improving the disintegration rate of the capsule. In addition, carboxymethyl cellulose, as a water-soluble polymer compound, can quickly absorb water and swell, promoting the rapid disintegration of the capsule wall, thereby improving the disintegration rate. At the same time, the addition of carboxymethyl cellulose can also improve the flexibility and rupture resistance of the capsule wall, further reducing brittleness; the addition of lactic acid can undergo an esterification reaction with hydroxypropyl starch to form a more stable network structure, increase the mechanical strength of the capsule wall, and reduce brittleness.

[0017] In summary, the use of lactic acid and carboxymethyl cellulose modified hydroxypropyl starch as the raw material for hollow capsules can enhance hydrophilicity, improve mechanical strength, optimize disintegration performance, and improve water absorption and swelling properties, thereby achieving a higher disintegration rate and lower friability compared to pregelatinized hydroxypropyl starch, thereby improving the overall performance of the capsule.

[0018] The preparation process of the modified hydroxypropyl starch comprises the following steps: N1: 15-25 parts by weight of starch is added to 60-90 parts by weight of water, and the mixture is stirred to obtain a starch emulsion. A swelling agent is added at a ratio of 2-6 wt% of the weight of the starch, and the mixture is heated at 80-100° C. for 1.5-2.5 h, cooled to room temperature, filtered, and washed to obtain a pre-swollen starch. N2: After mixing all the above pre-swollen starch, 60-90 parts by weight of water and 0.5-3 parts by weight of propylene oxide, adjust the pH to 11-12 with 1-3 mol / L sodium hydroxide aqueous solution, heat and react at 35-45°C for 10-24h, cool to room temperature, neutralize with 0.5-2 mol / L hydrochloric acid until the system is neutral, filter, wash, and dry to obtain hydroxypropyl starch; N3: Mix all the above hydroxypropyl starch and 40-70 parts by weight of water, and stir at 70-85° C. and 300-600 rpm for 30-70 min to obtain gelatinized hydroxypropyl starch; N4 Under a nitrogen atmosphere, add 0.3-1 parts by weight of lactic acid, 0.3-1 parts by weight of carboxymethyl cellulose and 0.01-0.1 parts by weight of amylase to the gelatinized hydroxypropyl starch, adjust the pH value to 5.-86.5, stir at 50-60°C and 200-600rpm for 1-3h, cool to room temperature, wash, filter and dry to obtain modified hydroxypropyl starch.

[0019] The starch is at least one of corn starch, tapioca starch, yam starch and potato starch.

[0020] The swelling agent is at least one of sodium hydroxide and potassium hydroxide.

[0021] The method for preparing the hydroxypropyl starch hollow capsules comprises the following steps: S1 weighs each raw material by weight; S2: When the water is heated to 70-85°C, hydroxypropyl starch is added, and the mixture is stirred at 400-800 rpm for 15-40 min, carrageenan is added and the mixture is stirred for 10-20 min, potassium chloride, pullulan, glycerin, and nano-titanium dioxide are added and the mixture is stirred for 20-40 min, and the mixture is gelled at 60-80°C for 3-7 h to obtain a sol; S3: placing the above sol at 35-45°C for dipping and molding, drying, placing at room temperature for 0.2-1 h, and finally demolding. After passing the quality inspection, cutting and fitting are performed to obtain hydroxypropyl starch hollow capsules.

[0022] Beneficial effects of the present invention: 1. The hydroxypropyl starch hollow capsules prepared by the present invention have certain stability and water resistance. The stability and solubility of the hydroxypropyl starch can be improved by introducing lactic acid into the hydroxypropyl starch for esterification reaction, thereby improving the dissolution rate and stability in the capsule; the esterification reaction can form a new ester bond between lactic acid and hydroxypropyl starch, thereby improving the solubility and bioavailability of the product, facilitating the release and absorption of the components in the capsule, and having a good disintegration rate and reducing friability.

[0023] 2. The hydroxypropyl starch hollow capsules prepared by the present invention open up a green channel for product export, are also suitable for various product types and formulas, have a high filling rate, and require greatly reduced auxiliary materials and additives compared with tablet products, which not only helps to create green food, but also saves production costs and improves production efficiency.

[0024] 3. The hydroxypropyl starch hollow capsules prepared by the present invention have a uniform surface, good gloss, good uniformity and stability, and good light-shielding properties, which meet the needs of the market and can be applied to the fields of medicines and health products. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 This is a physical picture of the product prepared in Example 1; Figure 2 This is the product test report prepared in Example 5. DETAILED DESCRIPTION

[0026] The above content of the present invention is further described in detail below in conjunction with specific implementation modes, but this should not be understood as the scope of the above subject matter of the present invention being limited to the following embodiments.

[0027] Example 1, a hydroxypropyl starch hollow capsule, composed of the following raw materials in parts by weight: 10 parts by weight of modified hydroxypropyl starch, 0.3 parts by weight of carrageenan, 0.02 parts by weight of potassium chloride, 0.15 parts by weight of pullulan, 0.1 parts by weight of glycerol, 0.03 parts by weight of nano titanium dioxide, 0.01 parts by weight of pigment, and 40 parts by weight of purified water.

[0028] The pigment is red iron oxide.

[0029] The preparation process of the modified hydroxypropyl starch comprises the following steps: N1: 20 parts by weight of corn starch is added to 80 parts by weight of purified water, and the mixture is stirred to obtain a starch emulsion. A swelling agent of 4 wt% of the weight of the starch is added, and the mixture is heated at 90°C for 2 hours, cooled to room temperature, filtered, and washed to obtain a pre-swollen starch; the swelling agent is sodium hydroxide; N2: After mixing all the above pre-swollen starch, 80 parts by weight of purified water and 2 parts by weight of propylene oxide, adjust the pH to 11.5 with a 2 mol / L sodium hydroxide aqueous solution, heat the mixture at 40°C for 16 hours, cool to room temperature, neutralize with 1 mol / L hydrochloric acid until the system is neutral, filter, wash and dry to obtain hydroxypropyl starch; N3: Mix all of the above hydroxypropyl starch and 60 parts by weight of purified water, and stir at 75° C. and 400 rpm for 45 min to obtain gelatinized hydroxypropyl starch; N4 Under a nitrogen atmosphere, 0.5 parts by weight of lactic acid, 0.5 parts by weight of carboxymethyl cellulose and 0.05 parts by weight of amylase (purchased from Chengdu Wanxiang Hongrun Biotechnology Co., Ltd., enzyme activity: 200,000 U / g) were added to the above-mentioned gelatinized hydroxypropyl starch, the pH value was adjusted to 6, the mixture was stirred at 55°C and 400 rpm for 1.5 h, cooled to room temperature, washed, filtered, and dried to obtain modified hydroxypropyl starch.

[0030] The preparation method of the hydroxypropyl starch hollow capsule comprises the following steps: S1 weighs each raw material by weight; S2: When purified water is heated to 78°C, modified hydroxypropyl starch is added, stirred at 600 rpm for 25 min, carrageenan is added and stirred for 15 min, potassium chloride, pullulan, glycerol, and nano-titanium dioxide are added and stirred for 30 min, and gelled at 70°C for 5 h to obtain a sol; S3: placing the above sol at 40°C for dipping and molding, drying, placing at room temperature for 0.5h, and finally demoulding. After passing the quality inspection, cutting and fitting are performed to obtain hydroxypropyl starch hollow capsules.

[0031] Example 2, a hydroxypropyl starch hollow capsule, composed of the following raw materials in parts by weight: 8 parts by weight of modified hydroxypropyl starch, 0.2 parts by weight of carrageenan, 0.01 parts by weight of potassium chloride, 0.01 parts by weight of pullulan, 0.01 parts by weight of glycerol, 0.005 parts by weight of nano titanium dioxide, 0.001 parts by weight of pigment, and 36 parts by weight of purified water.

[0032] The pigment is red iron oxide.

[0033] The preparation process of the modified hydroxypropyl starch comprises the following steps: N1: 15 parts by weight of corn starch is added to 60 parts by weight of purified water, and the mixture is stirred to obtain a starch emulsion. A swelling agent of 2 wt% of the weight of the starch is added, and the mixture is heated at 80°C for 1.5 hours, cooled to room temperature, filtered, and washed to obtain a pre-swollen starch; the swelling agent is sodium hydroxide; N2: After mixing all the above pre-swollen starch, 60 parts by weight of purified water and 0.5 parts by weight of propylene oxide, the pH value was adjusted to 11 with 1 mol / L sodium hydroxide aqueous solution, and the mixture was heated at 35°C for 10 hours, cooled to room temperature, and neutralized with 0.5 mol / L hydrochloric acid until the system was neutral, filtered, washed, and dried to obtain hydroxypropyl starch; N3: Mix all the above hydroxypropyl starch and 40 parts by weight of purified water, and stir at 70° C. and 300 rpm for 30 min to obtain gelatinized hydroxypropyl starch; N4 Under a nitrogen atmosphere, 0.3 parts by weight of lactic acid, 0.3 parts by weight of carboxymethyl cellulose and 0.01 parts by weight of amylase (purchased from Chengdu Wanxiang Hongrun Biotechnology Co., Ltd., enzyme activity: 200,000 U / g) were added to the above-mentioned gelatinized hydroxypropyl starch, the pH value was adjusted to 5.8, the mixture was stirred at 50°C and 200 rpm for 1 h, cooled to room temperature, washed, filtered, and dried to obtain modified hydroxypropyl starch.

[0034] The preparation method of the hydroxypropyl starch hollow capsule comprises the following steps: S1 weighs each raw material by weight; S2: When purified water is heated to 70°C, modified hydroxypropyl starch is added, stirred at 400 rpm for 15 min, carrageenan is added and stirred for 10 min, potassium chloride, pullulan, glycerol, and nano-titanium dioxide are added and stirred for 20 min, and gelled at 60°C for 3 h to obtain a sol; S3: placing the above sol at 35°C for dipping and molding, drying, placing at room temperature for 0.2h, and finally demoulding. After passing the quality inspection, cutting and fitting are performed to obtain hydroxypropyl starch hollow capsules.

[0035] Example 3, a hydroxypropyl starch hollow capsule, composed of the following raw materials in parts by weight: 14 parts by weight of modified hydroxypropyl starch, 0.36 parts by weight of carrageenan, 0.05 parts by weight of potassium chloride, 0.27 parts by weight of pullulan, 0.12 parts by weight of glycerol, 0.05 parts by weight of nano titanium dioxide, 0.02 parts by weight of pigment, and 45 parts by weight of purified water.

[0036] The pigment is red iron oxide.

[0037] The preparation process of the pregelatinized hydroxypropyl starch comprises the following steps: N1: 25 parts by weight of corn starch is added to 90 parts by weight of purified water, and the mixture is stirred to obtain a starch emulsion. A swelling agent of 6 wt% of the weight of the starch is added, and the mixture is heated at 100°C for 2.5 hours, cooled to room temperature, filtered, and washed to obtain a pre-swollen starch; the swelling agent is sodium hydroxide; N2: After mixing all the above pre-swollen starch, 90 parts by weight of purified water and 3 parts by weight of propylene oxide, adjust the pH to 12 with a 3 mol / L sodium hydroxide aqueous solution, heat the mixture at 45°C for 24 hours, cool to room temperature, neutralize with 2 mol / L hydrochloric acid until the system is neutral, filter, wash and dry to obtain hydroxypropyl starch; N3: Mix all the above hydroxypropyl starch and 70 parts by weight of purified water, and stir at 85° C. and 600 rpm for 70 min to obtain gelatinized hydroxypropyl starch; N4 Under a nitrogen atmosphere, 1 part by weight of lactic acid, 1 part by weight of carboxymethyl cellulose and 0.1 part by weight of amylase (purchased from Chengdu Wanxiang Hongrun Biotechnology Co., Ltd., enzyme activity: 200,000 U / g) were added to the above-mentioned gelatinized hydroxypropyl starch, the pH value was adjusted to 6.5, and the mixture was stirred at 60°C and 600 rpm for 3 h. The mixture was cooled to room temperature, washed, filtered and dried to obtain modified hydroxypropyl starch.

[0038] The preparation method of the hydroxypropyl starch hollow capsule comprises the following steps: S1 weighs each raw material by weight; S2: When purified water is heated to 85°C, modified hydroxypropyl starch is added, stirred at 800 rpm for 40 min, carrageenan is added and stirred for 20 min, potassium chloride, pullulan, glycerol and nano-titanium dioxide are added and stirred for 40 min, and gelled at 80°C for 7 h to obtain a sol; S3: placing the above sol at 45°C for dipping and molding, drying, placing at room temperature for 1 hour, and finally demoulding. After passing the quality inspection, cutting and fitting are performed to obtain hydroxypropyl starch hollow capsules.

[0039] Example 4, a hydroxypropyl starch hollow capsule, composed of the following raw materials in parts by weight: 10 parts by weight of hydroxypropyl starch, 0.3 parts by weight of carrageenan, 0.02 parts by weight of potassium chloride, 0.15 parts by weight of pullulan, 0.1 parts by weight of glycerol, 0.03 parts by weight of nano titanium dioxide, 0.01 parts by weight of pigment, and 40 parts by weight of purified water.

[0040] The pigment is red iron oxide.

[0041] The preparation process of the hydroxypropyl starch comprises the following steps: N1: 20 parts by weight of corn starch is added to 80 parts by weight of purified water, and the mixture is stirred to obtain a starch emulsion. A swelling agent of 4 wt% of the weight of the starch is added, and the mixture is heated at 90°C for 2 hours, cooled to room temperature, filtered, and washed to obtain a pre-swollen starch; the swelling agent is sodium hydroxide; N2: After mixing all the above-mentioned pre-swollen starch, 80 parts by weight of purified water and 2 parts by weight of propylene oxide, adjust the pH to 11.5 with a 2 mol / L sodium hydroxide aqueous solution, heat the reaction at 40°C for 16 hours, cool to room temperature, neutralize with 1 mol / L hydrochloric acid until the system is neutral, filter, wash, and dry to obtain hydroxypropyl starch.

[0042] The preparation method of the hydroxypropyl starch hollow capsule comprises the following steps: S1 weighs each raw material by weight; S2: When purified water is heated to 78°C, hydroxypropyl starch is added, and the mixture is stirred at 600 rpm for 25 min. Carrageenan is added and the mixture is stirred for 15 min. Potassium chloride, pullulan, glycerol, and nano-titanium dioxide are added and the mixture is stirred for 30 min. The mixture is gelled at 70°C for 5 h to obtain a sol. S3: placing the above sol at 40°C for dipping and molding, drying, placing at room temperature for 0.5h, and finally demoulding. After passing the quality inspection, cutting and fitting are performed to obtain hydroxypropyl starch hollow capsules.

[0043] Example 5, a hydroxypropyl starch hollow capsule, composed of the following raw materials in parts by weight: 10 parts by weight of pregelatinized hydroxypropyl starch, 0.3 parts by weight of carrageenan, 0.02 parts by weight of potassium chloride, 0.15 parts by weight of pullulan, 0.1 parts by weight of glycerol, 0.03 parts by weight of nano titanium dioxide, 0.01 parts by weight of pigment, and 40 parts by weight of purified water.

[0044] The pigment is red iron oxide.

[0045] The preparation process of the pregelatinized hydroxypropyl starch comprises the following steps: N1: 20 parts by weight of corn starch is added to 80 parts by weight of purified water, and the mixture is stirred to obtain a starch emulsion. A swelling agent of 4 wt% of the weight of the starch is added, and the mixture is heated at 90°C for 2 hours, cooled to room temperature, filtered, and washed to obtain a pre-swollen starch; the swelling agent is sodium hydroxide; N2: After mixing all the above pre-swollen starch, 80 parts by weight of purified water and 2 parts by weight of propylene oxide, adjust the pH to 11.5 with a 2 mol / L sodium hydroxide aqueous solution, heat the mixture at 40°C for 16 hours, cool to room temperature, neutralize with 1 mol / L hydrochloric acid until the system is neutral, filter, wash and dry to obtain hydroxypropyl starch; N3: All of the above hydroxypropyl starch was mixed with 60 parts by weight of purified water, and stirred at 75° C. and 400 rpm for 45 min to obtain pregelatinized hydroxypropyl starch.

[0046] The preparation method of the hydroxypropyl starch hollow capsule comprises the following steps: S1 weighs each raw material by weight; S2: When purified water is heated to 78°C, pregelatinized hydroxypropyl starch is added, stirred at 600 rpm for 25 min, carrageenan is added and stirred for 15 min, potassium chloride, pullulan, glycerol and nano-titanium dioxide are added and stirred for 30 min, and gelled at 70°C for 5 h to obtain a sol; S3: placing the above sol at 40°C for dipping and molding, drying, placing at room temperature for 0.5h, and finally demoulding. After passing the quality inspection, cutting and fitting are performed to obtain hydroxypropyl starch hollow capsules.

[0047] Example 6, a hydroxypropyl starch hollow capsule, composed of the following raw materials in parts by weight: 10 parts by weight of modified starch, 0.3 parts by weight of carrageenan, 0.02 parts by weight of potassium chloride, 0.15 parts by weight of pullulan, 0.1 parts by weight of glycerol, 0.03 parts by weight of nano titanium dioxide, 0.01 parts by weight of pigment, and 40 parts by weight of purified water.

[0048] The pigment is red iron oxide.

[0049] The preparation process of the modified starch comprises the following steps: N1: 20 parts by weight of corn starch is added to 80 parts by weight of purified water, and the mixture is stirred to obtain a starch emulsion. A swelling agent of 4 wt% of the weight of the starch is added, and the mixture is heated at 90°C for 2 hours, cooled to room temperature, filtered, and washed to obtain a pre-swollen starch; the swelling agent is sodium hydroxide; N2 Under a nitrogen atmosphere, 0.5 parts by weight of lactic acid, 0.5 parts by weight of carboxymethyl cellulose and 0.05 parts by weight of amylase (purchased from Chengdu Wanxiang Hongrun Biotechnology Co., Ltd., enzyme activity: 200,000 U / g) were added to the pre-swollen starch, the pH value was adjusted to 6, the mixture was stirred at 55°C and 400 rpm for 1.5 h, cooled to room temperature, washed, filtered, and dried to obtain modified starch.

[0050] The preparation method of the hydroxypropyl starch hollow capsule comprises the following steps: S1 weighs each raw material by weight; S2: When purified water is heated to 78°C, modified starch is added, stirred at 600 rpm for 25 min, carrageenan is added and stirred for 15 min, potassium chloride, pullulan, glycerol, and nano-titanium dioxide are added and stirred for 30 min, and gelled at 70°C for 5 h to obtain a sol; S3: placing the above sol at 40°C for dipping and molding, drying, placing at room temperature for 0.5h, and finally demoulding. After passing the quality inspection, cutting and fitting are performed to obtain hydroxypropyl starch hollow capsules.

[0051] Test Example 1, disintegration performance test of hydroxypropyl starch hollow capsules: The disintegration time was tested according to the method in the appendix of the 2020 version of the "Chinese Pharmacopoeia". The hydroxypropyl starch hollow capsules prepared in Examples 1-6 were subjected to initial disintegration time testing in an artificial gastric fluid environment, and then the compound soft capsule shells were placed in an intelligent disintegrator for accelerated aging at a temperature of 40°C and a relative humidity of 75%. Some samples were taken out at 60d and 120d for disintegration time testing and stability testing, and the results are shown in Tables 1 and 2.

[0052] Table 1 Determination results of disintegration time of hydroxypropyl starch empty capsules

[0053] Test Example 2, friability test: 200 hydroxypropyl starch hollow capsules prepared in Example 1 and Example 4-3 were taken each time, placed in a watch glass, dried in an oven at 40°C for 24 hours, taken out, and placed one by one in a glass tube erected on a 2 cm thick wooden board. A cylindrical weight with a mass of 20 grams was freely dropped from the glass mouth to observe whether the capsules were broken, and the number of friability was calculated. The results are shown in Table 2.

[0054] Table 2 Determination results of brittleness of hydroxypropyl starch empty capsules

[0055] As can be seen from the above results, the hydroxypropyl starch hollow capsules prepared by the present invention have good disintegration time, and the friability is very low, and the capsules have good stability and disintegration performance. As can be seen from Example 1 and Example 5, pregelatinized hydroxypropyl starch has better disintegration performance and lower friability than non-gelatinized capsules. The reason is that the hydroxyl groups on the starch molecular chain react with propylene oxide to introduce hydroxypropoxy groups, which increase the hydrophilicity of the starch molecules and improve their water absorption and swelling properties. Part or all of the starch granules are destroyed by physical methods. This treatment method makes the structure of the starch granules looser and can form a more uniform and tough capsule wall. This uniformity helps to improve the mechanical strength of the capsule and reduce the risk of breakage during storage and transportation; At the same time, it has better freeze-thaw stability and solubility in cold water, improves its ability to absorb water and swell, and this enhanced water absorption is conducive to the rapid disintegration of the capsule in vivo, and improves the release rate of the drug. Further comparing Example 1 with Example 4 and Example 6, the hollow capsules prepared by modified hydroxypropyl starch have better disintegration performance and lower friability. The addition of lactic acid and carboxymethyl cellulose can improve the water absorption and swelling of hydroxypropyl starch, which helps the capsule to quickly absorb water and swell in the body, thereby improving the disintegration rate of the capsule. In addition, carboxymethyl cellulose, as a water-soluble polymer compound, can quickly absorb water and swell, promote the rapid disintegration of the capsule wall, thereby improving the disintegration rate. At the same time, the addition of carboxymethyl cellulose can also improve the flexibility and anti-rupture ability of the capsule wall, further reducing the friability; the addition of lactic acid can undergo an esterification reaction with hydroxypropyl starch to form a more stable network structure, increase the mechanical strength of the capsule wall, and reduce the friability.

[0056] In summary, the use of lactic acid and carboxymethyl cellulose modified hydroxypropyl starch as the raw material for hollow capsules can enhance hydrophilicity, improve mechanical strength, optimize disintegration performance, and improve water absorption and swelling properties, thereby achieving a higher disintegration rate and lower friability compared to pregelatinized hydroxypropyl starch, thereby improving the overall performance of the capsule.

Claims

1. A hydroxypropyl starch hollow capsule, characterized in that: The invention is composed of the following raw materials in parts by weight: 5-20 parts by weight of hydroxypropyl starch, 0.1-0.6 parts by weight of carrageenan, 0-0.1 parts by weight of potassium chloride, 0-0.5 parts by weight of pullulan, 0-0.3 parts by weight of glycerol, 0-0.1 parts by weight of nano titanium dioxide, 0-0.05 parts by weight of pigment and 20-50 parts by weight of water.

2. The hydroxypropyl starch hollow capsule according to claim 1, characterized in that The invention is composed of the following raw materials in parts by weight: 8-14 parts by weight of hydroxypropyl starch, 0.2-0.36 parts by weight of carrageenan, 0.01-0.05 parts by weight of potassium chloride, 0.01-0.27 parts by weight of pullulan, 0.01-0.12 parts by weight of glycerol, 0.005-0.05 parts by weight of nano titanium dioxide, 0.001-0.02 parts by weight of pigment and 35-45 parts by weight of water.

3. The hydroxypropyl starch hollow capsule according to claim 1 or 2, characterized in that: The hydroxypropyl starch is pregelatinized hydroxypropyl starch or modified hydroxypropyl starch.

4. The hydroxypropyl starch hollow capsule according to claim 1 or 2, characterized in that: The pigment is any one of synthetic pigment, natural pigment, plant pigment, red iron oxide and yellow iron oxide.

5. The hydroxypropyl starch hollow capsule according to claim 3, characterized in that: The preparation process of the pregelatinized hydroxypropyl starch comprises the following steps: N1: 15-25 parts by weight of starch is added to 60-90 parts by weight of water, and the mixture is stirred to obtain a starch emulsion. A swelling agent is added at a ratio of 2-6 wt% of the weight of the starch, and the mixture is heated at 80-100° C. for 1.5-2.5 h, cooled to room temperature, filtered, and washed to obtain a pre-swollen starch. N2: After mixing all the above pre-swollen starch, 60-90 parts by weight of water and 0.5-3 parts by weight of propylene oxide, adjust the pH to 11-12 with 1-3 mol / L sodium hydroxide aqueous solution, heat and react at 35-45°C for 10-24h, cool to room temperature, neutralize with 0.5-2 mol / L hydrochloric acid until the system is neutral, filter, wash, and dry to obtain hydroxypropyl starch; N3: Mix all the above hydroxypropyl starch with 40-70 parts by weight of water, and stir at 70-85° C. and 300-600 rpm for 30-70 min to obtain pregelatinized hydroxypropyl starch.

6. The hydroxypropyl starch hollow capsule according to claim 3, characterized in that: The preparation process of the modified hydroxypropyl starch comprises the following steps: N1: add 15-25 parts of starch to 60-90 parts by weight of water, stir evenly to obtain a starch emulsion, then add a swelling agent at 2-6 wt% of the weight of the starch, heat at 80-100°C for reaction for 1.5-2.5h, cool to room temperature, filter and wash to obtain a pre-swollen starch; N2: After mixing all the above pre-swollen starch, 60-90 parts by weight of water and 0.5-3 parts by weight of propylene oxide, adjust the pH to 11-12 with 1-3 mol / L sodium hydroxide aqueous solution, heat and react at 35-45°C for 10-24h, cool to room temperature, neutralize with 0.5-2 mol / L hydrochloric acid until the system is neutral, filter, wash, and dry to obtain hydroxypropyl starch; N3: Mix all the above hydroxypropyl starch and 40-70 parts by weight of water, and stir at 70-85° C. and 300-600 rpm for 30-70 min to obtain gelatinized hydroxypropyl starch; N4 Under a nitrogen atmosphere, add 0.3-1 parts by weight of lactic acid, 0.3-1 parts by weight of carboxymethyl cellulose and 0.01-0.1 parts by weight of amylase to the gelatinized hydroxypropyl starch, adjust the pH value to 5.-86.5, stir at 50-60°C and 200-600rpm for 1-3h, cool to room temperature, wash, filter and dry to obtain modified hydroxypropyl starch.

7. The hydroxypropyl starch hollow capsule according to claim 5 or 6, characterized in that: The starch is at least one of corn starch, tapioca starch, yam starch and potato starch.

8. The hydroxypropyl starch hollow capsule according to claim 5 or 6, characterized in that: The swelling agent is at least one of sodium hydroxide and potassium hydroxide.

9. The method for preparing hydroxypropyl starch hollow capsules according to any one of claims 1 to 8, characterized in that: The steps include: S1 weighs each raw material by weight; S2: When the water is heated to 70-85°C, hydroxypropyl starch is added and stirred, carrageenan is added and stirred continuously, potassium chloride, pullulan, glycerin and nano-titanium dioxide are added and stirred continuously, and heated and gelled to obtain a sol; S3: forming the sol by dipping into glue, drying, demoulding, cutting and fitting, so as to obtain the hydroxypropyl starch hollow capsule.

Images