Hydroxypropyl starch hollow capsules and a process for their production

Abstract

The present application relates to the technical field of capsules, in particular to a kind of hydroxypropyl starch hollow capsule and preparation method thereof.The hydroxypropyl starch hollow capsule is composed of the following weight parts of raw materials: 5-20 weight parts of hydroxypropyl starch, 0.1-0.6 weight parts of carrageenan, 0-0.1 weight parts of potassium chloride, 0-0.5 weight parts of pullulan, 0-0.3 weight parts of glycerol, 0-0.1 weight parts of nano titanium dioxide, 0-0.05 weight parts of pigment, 20-50 weight parts of water.By adding modified hydroxypropyl starch, the stability and solubility of hydroxypropyl starch can be improved, thereby improving the dissolution rate and stability in the capsule, improving the solubility and bioavailability of the product, helping the release and absorption of the components in the capsule, and also having good disintegration rate, and can also reduce the friability.

Description

Technical Field

[0001] This invention relates to the field of capsule technology, specifically to a hydroxypropyl starch empty capsule and its preparation method. Background Technology

[0002] Hydroxypropyl starch empty capsules are a novel oral medication dosage form composed of hydroxypropyl starch and other excipients. They are typically semi-transparent hard-shell capsules and primarily used for oral medications. With increasing concerns about food safety and the safety of animal products, the limitations of gelatin capsules have become increasingly apparent, such as susceptibility to acids and alkalis, sensitivity to environmental temperature and humidity, and potential risks of animal disease. Therefore, hydroxypropyl starch empty capsules, as an alternative, have attracted attention in research and development due to their wide availability of raw materials, high safety, and excellent disintegration and friability properties.

[0003] Key technologies in the preparation of hydroxypropyl starch empty capsules include selecting suitable hydroxypropyl starch raw materials, adjusting the degree of substitution, and optimizing the sol-gel and drying processes. The degree of substitution of hydroxypropyl starch has a significant impact on the performance of the capsules. Studies have shown that when the degree of substitution is between 1.5% and 4.6%, the prepared starch empty capsules all meet the requirements of the 2015 edition of the Pharmacopoeia of the People's Republic of China, with the empty capsules exhibiting the best performance when the degree of substitution is 2.3%.

[0004] Furthermore, the preparation methods for hydroxypropyl starch empty capsules are constantly being innovated. For example, one method for preparing hydroxypropyl starch empty capsules includes mixing hydroxypropyl starch, a gelling agent, and a coagulant with water in a certain proportion, stirring evenly, and then placing the mixture in a water bath at a set temperature to gelatinize the starch. Then, glycerol and nano-ultrafine calcium carbonate are added, stirred evenly to form a gel solution, and allowed to stand to remove air bubbles from the gel solution. Finally, capsule blanks are prepared using a fully automated empty capsule manufacturing machine and dried.

[0005] In terms of raw material selection, the preparation of hydroxypropyl starch empty capsules utilizes starch as a raw material, which is inexpensive and low-cost. It also avoids the environmental pollution problems caused by wastewater discharge in traditional gelatin product production. This capsule preparation method not only improves product quality and stability but also has environmental advantages. In summary, the research and development of hydroxypropyl starch empty capsules aims to provide a novel empty capsule with superior performance, high safety, low cost, and environmental friendliness to meet the needs of the pharmaceutical, food, and health product industries. With continuous technological advancements and innovation, hydroxypropyl starch empty capsules are expected to become an important direction for future pharmaceutical dosage form development. Summary of the Invention

[0006] To address the shortcomings of the existing technology, this invention provides a hydroxypropyl starch empty capsule and its preparation method.

[0007] To solve the above-mentioned technical problems, the technical solution adopted by the present invention is as follows:

[0008] A hydroxypropyl starch empty capsule is composed of the following raw materials in parts by weight: 5-20 parts hydroxypropyl starch, 0.1-0.6 parts carrageenan, 0-0.1 parts potassium chloride, 0-0.5 parts pullulan, 0-0.3 parts glycerol, 0-0.1 parts nano titanium dioxide, 0-0.05 parts pigment, and 20-50 parts water.

[0009] Preferably, the hydroxypropyl starch empty capsule is composed of the following raw materials in parts by weight: 8-14 parts hydroxypropyl starch, 0.2-0.36 parts carrageenan, 0.01-0.05 parts potassium chloride, 0.01-0.27 parts pullulan, 0.01-0.12 parts glycerol, 0.005-0.05 parts nano titanium dioxide, 0.001-0.02 parts pigment, and 35-45 parts water.

[0010] More preferably, the hydroxypropyl starch empty capsule is 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.

[0011] The hydroxypropyl starch is pregelatinized hydroxypropyl starch or modified hydroxypropyl starch.

[0012] The pigment is any one of synthetic pigments, natural pigments, plant pigments, iron oxide red, and iron oxide yellow.

[0013] Unlike gelatin capsules, hydroxypropyl starch capsules are non-animal-derived products, made primarily from pregelatinized or modified hydroxypropyl starch as the film-forming material. Over 90% of the components in hydroxypropyl starch capsules are pregelatinized hydroxypropyl starch; therefore, their basic characteristics are mainly determined by the properties of hydroxypropyl starch. Hydroxypropyl starch is a soluble starch derivative. Chemically, hydroxypropyl groups are introduced into the starch backbone, giving the starch molecules better water solubility and reduced viscosity. It is also a relatively stable substance, with stable solution properties, undergoing a sol-gel transition during heating and cooling. Hydroxypropyl starch possesses excellent film-forming, dispersible, and adhesive properties, and has excellent compatibility with most substances. Therefore, hydroxypropyl starch capsules do not carry the risk of cross-linking reactions, have high chemical stability, and high water retention, effectively solving the problem of capsule fragility.

[0014] In the preparation of pregelatinized hydroxypropyl starch, the hydroxyl groups on the starch molecular chains react with propylene oxide to introduce hydroxypropoxy groups. These hydroxypropoxy groups increase the hydrophilicity of the starch molecules, improving their water absorption and swelling properties. Physical methods are used to break down some or all of the starch granules, resulting in a looser structure that forms more uniform and robust capsule walls. This uniformity helps improve the mechanical strength of the capsules, reducing the risk of breakage during storage and transportation. Simultaneously, it provides better freeze-thaw stability and solubility in cold water, enhancing its water absorption and swelling capacity. This enhanced water absorption facilitates rapid disintegration of the capsules in vivo, increasing the drug release rate.

[0015] The preparation process of the pregelatinized hydroxypropyl starch includes the following steps:

[0016] N1 Take 15-25 parts by weight of starch and add it to 60-90 parts by weight of water. Stir well to obtain starch emulsion. Then add 2-6 wt% of the starch weight of swelling agent. Heat the mixture at 80-100℃ for 1.5-2.5 hours. Cool to room temperature, filter and wash to obtain pre-swollen starch.

[0017] N2 mixes all the above pre-swollen starch, 60-90 parts by weight of water and 0.5-3 parts by weight of propylene oxide, adjusts the pH to 11-12 with 1-3 mol / L sodium hydroxide aqueous solution, heats and reacts at 35-45℃ for 10-24 h, cools to room temperature, neutralizes the system with 0.5-2 mol / L hydrochloric acid until the system is neutral, filters, washes and dries to obtain hydroxypropyl starch;

[0018] N3 mixes all of the above hydroxypropyl starch with 40-70 parts by weight of water and stirs at 70-85°C and 300-600 rpm for 30-70 minutes to obtain pregelatinized hydroxypropyl starch.

[0019] Pregelatinized hydroxypropyl starch, as a modified starch, already possesses many excellent properties, such as good disintegration, adhesion, solubility, and freeze-thaw stability, making it widely used in pharmaceuticals, food, and other fields. However, to further expand its application range, improve performance, or reduce costs, further modifications are needed based on pregelatinized hydroxypropyl starch.

[0020] The addition of lactic acid and carboxymethyl cellulose can improve the water absorption and swelling properties of hydroxypropyl starch, which helps the capsules to quickly absorb water and swell in the body, thereby increasing the disintegration rate. Furthermore, carboxymethyl cellulose, as a water-soluble polymer, can rapidly absorb water and swell, promoting rapid disintegration of the capsule wall and thus increasing the disintegration rate. Simultaneously, 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, increasing the mechanical strength of the capsule wall and reducing brittleness.

[0021] In summary, using lactic acid and carboxymethyl cellulose-modified hydroxypropyl starch as the raw material for empty capsules can improve the overall performance of the capsules by enhancing hydrophilicity, increasing mechanical strength, optimizing disintegration performance, and improving water absorption and swelling properties, thereby achieving a higher disintegration rate and lower brittleness compared to pregelatinized hydroxypropyl starch.

[0022] The preparation process of the modified hydroxypropyl starch includes the following steps:

[0023] N1 Take 15-25 parts by weight of starch and add it to 60-90 parts by weight of water. Stir well to obtain starch emulsion. Then add 2-6 wt% of the starch weight of swelling agent. Heat the mixture at 80-100℃ for 1.5-2.5 hours. Cool to room temperature, filter and wash to obtain pre-swollen starch.

[0024] N2 mixes all the above pre-swollen starch, 60-90 parts by weight of water and 0.5-3 parts by weight of propylene oxide, adjusts the pH to 11-12 with 1-3 mol / L sodium hydroxide aqueous solution, heats and reacts at 35-45℃ for 10-24 h, cools to room temperature, neutralizes the system with 0.5-2 mol / L hydrochloric acid until the system is neutral, filters, washes and dries to obtain hydroxypropyl starch;

[0025] N3 mixes all of the above hydroxypropyl starch with 40-70 parts by weight of water and stirs at 70-85°C and 300-600 rpm for 30-70 minutes to obtain gelatinized hydroxypropyl starch.

[0026] Under a nitrogen atmosphere, 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 were added to the above gelatinized hydroxypropyl starch. The pH was adjusted to 5.-86.5. The mixture was stirred at 50-60℃ and 200-600 rpm for 1-3 hours, cooled to room temperature, washed, filtered, and dried to obtain modified hydroxypropyl starch.

[0027] The starch is at least one of corn starch, tapioca starch, yam starch, and potato starch.

[0028] The swelling agent is at least one of sodium hydroxide and potassium hydroxide.

[0029] The method for preparing hydroxypropyl starch empty capsules includes the following steps:

[0030] S1 Weigh each raw material according to the weight parts;

[0031] S2 heats water to 70-85℃, adds hydroxypropyl starch, stirs at 400-800 rpm for 15-40 min, adds carrageenan and continues stirring for 10-20 min, then adds potassium chloride, pullulan, glycerol, and nano titanium dioxide and continues stirring for 20-40 min, gelling at 60-80℃ for 3-7 h to obtain a sol;

[0032] S3 The above sol is placed at 35-45℃ for dipping and molding, dried, placed at room temperature for 0.2-1 h, and finally demolded. After passing quality inspection, it is cut and assembled to obtain hydroxypropyl starch hollow capsules.

[0033] The beneficial effects of this invention are:

[0034] 1. The hydroxypropyl starch hollow capsules prepared by this invention have certain stability and water resistance. The esterification reaction by introducing lactic acid into hydroxypropyl starch can improve the stability and solubility of hydroxypropyl starch, thereby improving the dissolution rate and stability in the capsule. The esterification reaction can form new ester bonds between lactic acid and hydroxypropyl starch, improving the solubility and bioavailability of the product, which helps the release and absorption of the components in the capsule. At the same time, it has a good disintegration rate and can also reduce brittleness.

[0035] 2. The hydroxypropyl starch empty capsules prepared by this invention open up a green channel for product export and are suitable for various product types and formulations. They have a high filling rate and, compared with tablet products, require significantly fewer excipients and additives. This not only helps to create green food but also saves production costs and improves production efficiency.

[0036] 3. The hydroxypropyl starch hollow capsules prepared by this invention have a uniform surface, good gloss, good uniformity and stability, and good light-blocking properties, which meet market demands and can be applied in the fields of pharmaceuticals and health products. Attached Figure Description

[0037] Figure 1 A photograph of the product prepared in Example 1;

[0038] Figure 2 The product test report prepared in Example 5. Detailed Implementation

[0039] The invention will now be described in further detail with reference to specific embodiments, but it should not be construed as limiting the scope of the invention to the following embodiments.

[0040] Example 1: A hydroxypropyl starch empty 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.

[0041] The pigment is iron oxide red.

[0042] The preparation process of the modified hydroxypropyl starch includes the following steps:

[0043] N1 Take 20 parts by weight of corn starch and add it to 80 parts by weight of purified water. Stir well to obtain starch emulsion. Then add 4 wt% of the starch weight of swelling agent. Heat the mixture at 90°C for 2 hours. Cool to room temperature, filter and wash to obtain pre-swollen starch. The swelling agent is sodium hydroxide.

[0044] N2 mixes all of the above pre-swollen starch, 80 parts by weight of purified water and 2 parts by weight of propylene oxide, adjusts the pH to 11.5 with 2 mol / L sodium hydroxide aqueous solution, heats the reaction at 40°C for 16 h, cools to room temperature, neutralizes the system with 1 mol / L hydrochloric acid until the system is neutral, filters, washes and dries to obtain hydroxypropyl starch.

[0045] N3 mixed all of the above hydroxypropyl starch with 60 parts by weight of purified water and stirred at 75°C and 400 rpm for 45 min to obtain gelatinized hydroxypropyl starch.

[0046] 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 gelatinized hydroxypropyl starch. The pH was adjusted to 6, and the mixture was stirred at 55℃ and 400 rpm for 1.5 h. After cooling to room temperature, the starch was washed, filtered, and dried to obtain modified hydroxypropyl starch.

[0047] The method for preparing the hydroxypropyl starch empty capsules includes the following steps:

[0048] S1 Weigh each raw material according to the weight parts;

[0049] S2 heated purified water to 78°C, added modified hydroxypropyl starch, stirred at 600 rpm for 25 min, added carrageenan and continued stirring for 15 min, then added potassium chloride, pullulan, glycerol and nano titanium dioxide and continued stirring for 30 min, and gelled at 70°C for 5 h to obtain sol.

[0050] S3 dips the above sol into the sol at 40°C to form a shape, dries it, places it at room temperature for 0.5 hours, and finally demolds it. After passing quality inspection, it is cut and assembled to obtain hydroxypropyl starch hollow capsules.

[0051] Example 2: A hydroxypropyl starch empty 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.

[0052] The pigment is iron oxide red.

[0053] The preparation process of the modified hydroxypropyl starch includes the following steps:

[0054] N1. Take 15 parts by weight of corn starch and add it to 60 parts by weight of purified water. Stir well to obtain starch emulsion. Then add 2 wt% of starch weight of swelling agent. Heat the mixture at 80°C for 1.5 hours. Cool to room temperature, filter and wash to obtain pre-swollen starch. The swelling agent is sodium hydroxide.

[0055] N2 mixes all of the above pre-swollen starch, 60 parts by weight of purified water and 0.5 parts by weight of propylene oxide, adjusts the pH to 11 with 1 mol / L sodium hydroxide aqueous solution, heats and reacts at 35°C for 10 h, cools to room temperature, neutralizes the system with 0.5 mol / L hydrochloric acid to neutral, filters, washes and dries to obtain hydroxypropyl starch.

[0056] N3 mixed all of the above hydroxypropyl starch with 40 parts by weight of purified water and stirred at 70°C and 300 rpm for 30 min to obtain gelatinized hydroxypropyl starch.

[0057] 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 gelatinized hydroxypropyl starch. The pH was adjusted to 5.8, and the mixture was stirred at 50°C and 200 rpm for 1 hour. After cooling to room temperature, the starch was washed, filtered, and dried to obtain modified hydroxypropyl starch.

[0058] The method for preparing the hydroxypropyl starch empty capsules includes the following steps:

[0059] S1 Weigh each raw material according to the weight parts;

[0060] S2 heated purified water to 70°C, added modified hydroxypropyl starch, stirred at 400 rpm for 15 min, added carrageenan and continued stirring for 10 min, then added potassium chloride, pullulan, glycerol and nano titanium dioxide and continued stirring for 20 min, and gelled at 60°C for 3 h to obtain sol.

[0061] S3 dips the above sol into the sol at 35°C to form a shape, dries it, places it at room temperature for 0.2 hours, and finally demolds it. After passing quality inspection, it is cut and assembled to obtain hydroxypropyl starch hollow capsules.

[0062] Example 3: A hydroxypropyl starch empty 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.

[0063] The pigment is iron oxide red.

[0064] The preparation process of the pregelatinized hydroxypropyl starch includes the following steps:

[0065] N1. Take 25 parts by weight of corn starch and add it to 90 parts by weight of purified water. Stir well to obtain starch emulsion. Then add 6 wt% of starch weight of swelling agent. Heat the mixture at 100°C for 2.5 hours. Cool to room temperature, filter and wash to obtain pre-swollen starch. The swelling agent is sodium hydroxide.

[0066] N2 mixes all of the above pre-swollen starch, 90 parts by weight of purified water and 3 parts by weight of propylene oxide, adjusts the pH to 12 with 3 mol / L sodium hydroxide aqueous solution, heats the reaction at 45°C for 24 h, cools to room temperature, neutralizes the system with 2 mol / L hydrochloric acid to neutral, filters, washes and dries to obtain hydroxypropyl starch.

[0067] N3 mixed all of the above hydroxypropyl starch with 70 parts by weight of purified water and stirred at 85°C and 600 rpm for 70 min to obtain gelatinized hydroxypropyl starch.

[0068] 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 gelatinized hydroxypropyl starch. The pH was adjusted to 6.5, and the mixture was stirred at 60℃ and 600 rpm for 3 hours. After cooling to room temperature, the starch was washed, filtered, and dried to obtain modified hydroxypropyl starch.

[0069] The method for preparing the hydroxypropyl starch empty capsules includes the following steps:

[0070] S1 Weigh each raw material according to the weight parts;

[0071] S2 heated purified water to 85°C, added modified hydroxypropyl starch, stirred at 800 rpm for 40 min, added carrageenan and continued stirring for 20 min, then added potassium chloride, pullulan, glycerol and nano titanium dioxide and continued stirring for 40 min, and gelled at 80°C for 7 h to obtain sol.

[0072] S3 dips the above sol into the sol at 45°C to form a shape, dries it, places it at room temperature for 1 hour, and finally demolds it. After passing quality inspection, it is cut and assembled to obtain hydroxypropyl starch hollow capsules.

[0073] Example 4: A hydroxypropyl starch empty 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.

[0074] The pigment is iron oxide red.

[0075] The preparation process of the hydroxypropyl starch includes the following steps:

[0076] N1 Take 20 parts by weight of corn starch and add it to 80 parts by weight of purified water. Stir well to obtain starch emulsion. Then add 4 wt% of the starch weight of swelling agent. Heat the mixture at 90°C for 2 hours. Cool to room temperature, filter and wash to obtain pre-swollen starch. The swelling agent is sodium hydroxide.

[0077] N2 mixed all of the above pre-swollen starch, 80 parts by weight of purified water and 2 parts by weight of propylene oxide, adjusted the pH to 11.5 with 2 mol / L sodium hydroxide aqueous solution, heated the reaction at 40°C for 16 h, cooled to room temperature, neutralized the system with 1 mol / L hydrochloric acid until the system was neutral, filtered, washed and dried to obtain hydroxypropyl starch.

[0078] The method for preparing the hydroxypropyl starch empty capsules includes the following steps:

[0079] S1 Weigh each raw material according to the weight parts;

[0080] S2 heated purified water to 78°C, added hydroxypropyl starch, stirred at 600 rpm for 25 min, added carrageenan and continued stirring for 15 min, then added potassium chloride, pullulan, glycerol and nano titanium dioxide and continued stirring for 30 min, and gelled at 70°C for 5 h to obtain sol.

[0081] S3 dips the above sol into the sol at 40°C to form a shape, dries it, places it at room temperature for 0.5 hours, and finally demolds it. After passing quality inspection, it is cut and assembled to obtain hydroxypropyl starch hollow capsules.

[0082] Example 5: A hydroxypropyl starch empty 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.

[0083] The pigment is iron oxide red.

[0084] The preparation process of the pregelatinized hydroxypropyl starch includes the following steps:

[0085] N1 Take 20 parts by weight of corn starch and add it to 80 parts by weight of purified water. Stir well to obtain starch emulsion. Then add 4 wt% of the starch weight of swelling agent. Heat the mixture at 90°C for 2 hours. Cool to room temperature, filter and wash to obtain pre-swollen starch. The swelling agent is sodium hydroxide.

[0086] N2 mixes all of the above pre-swollen starch, 80 parts by weight of purified water and 2 parts by weight of propylene oxide, adjusts the pH to 11.5 with 2 mol / L sodium hydroxide aqueous solution, heats the reaction at 40°C for 16 h, cools to room temperature, neutralizes the system with 1 mol / L hydrochloric acid until the system is neutral, filters, washes and dries to obtain hydroxypropyl starch.

[0087] N3 mixed all of the above hydroxypropyl starch with 60 parts by weight of purified water and stirred at 75°C and 400 rpm for 45 min to obtain pregelatinized hydroxypropyl starch.

[0088] The method for preparing the hydroxypropyl starch empty capsules includes the following steps:

[0089] S1 Weigh each raw material according to the weight parts;

[0090] S2 heated purified water to 78°C, added pregelatinized hydroxypropyl starch, stirred at 600 rpm for 25 min, added carrageenan and continued stirring for 15 min, then added potassium chloride, pullulan, glycerol and nano titanium dioxide and continued stirring for 30 min, gelled at 70°C for 5 h to obtain sol;

[0091] S3 dips the above sol into the sol at 40°C to form a shape, dries it, places it at room temperature for 0.5 hours, and finally demolds it. After passing quality inspection, it is cut and assembled to obtain hydroxypropyl starch hollow capsules.

[0092] Example 6: A hydroxypropyl starch empty 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.

[0093] The pigment is iron oxide red.

[0094] The preparation process of the modified starch includes the following steps:

[0095] N1 Take 20 parts by weight of corn starch and add it to 80 parts by weight of purified water. Stir well to obtain starch emulsion. Then add 4 wt% of the starch weight of swelling agent. Heat the mixture at 90°C for 2 hours. Cool to room temperature, filter and wash to obtain pre-swollen starch. The swelling agent is sodium hydroxide.

[0096] 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 was adjusted to 6, and the mixture was stirred at 55°C and 400 rpm for 1.5 h. After cooling to room temperature, the starch was washed, filtered, and dried to obtain modified starch.

[0097] The method for preparing the hydroxypropyl starch empty capsules includes the following steps:

[0098] S1 Weigh each raw material according to the weight parts;

[0099] S2 heated purified water to 78°C, added modified starch, stirred at 600 rpm for 25 min, added carrageenan and continued stirring for 15 min, then added potassium chloride, pullulan, glycerol and nano titanium dioxide and continued stirring for 30 min, and gelled at 70°C for 5 h to obtain sol.

[0100] S3 dips the above sol into the sol at 40°C to form a shape, dries it, places it at room temperature for 0.5 hours, and finally demolds it. After passing quality inspection, it is cut and assembled to obtain hydroxypropyl starch hollow capsules.

[0101] Test Example 1: Disintegration performance test of hydroxypropyl starch empty capsules: The disintegration time was tested according to the method in the appendix of the 2020 edition of the Chinese Pharmacopoeia. The hydroxypropyl starch empty capsules prepared in Examples 1-6 were tested for initial disintegration time in an artificial gastric fluid environment. Then, the compound soft capsule shells were placed in an intelligent disintegration apparatus and accelerated aging was carried out at a temperature of 40°C and a relative humidity of 75%. Samples were taken out at 60 days and 120 days for disintegration time and stability tests, respectively. The results are shown in Tables 1 and 2.

[0102] Table 1 Results of the determination of disintegration time of hydroxypropyl starch empty capsules

[0103]

[0104] Test Example 2, Friability Test: 200 hydroxypropyl starch empty capsules prepared in Examples 1 and 4-3 were taken each time, placed in a petri dish, dried in an oven at 40°C for 24 hours, and then placed one capsule at a time into a glass tube standing upright on a 2cm thick wooden board. A cylindrical weight of 20g was dropped freely from the glass opening, and the capsules were observed to see if they broke. The number of brittle capsules was calculated, and the results are shown in Table 2.

[0105] Table 2. Results of caloric starch empty capsule brittleness determination

[0106]

[0107] The results above show that the hydroxypropyl starch hollow capsules prepared by this invention have good disintegration time and low friability, exhibiting good stability and disintegration performance. Examples 1 and 5 demonstrate that pregelatinized hydroxypropyl starch has better disintegration performance and lower friability compared to ungelatinized capsules. This is because the hydroxyl groups on the starch molecular chain react with propylene oxide, introducing hydroxypropoxy groups. These hydroxypropoxy groups increase the hydrophilicity of the starch molecules, improving their water absorption and swelling properties. Physically destroying some or all of the starch granules makes the starch granule structure looser, resulting in a more uniform and tougher capsule wall. This uniformity helps improve the mechanical strength of the capsules and reduces the risk of breakage during storage and transportation. Simultaneously, it provides better freeze-thaw stability and solubility in cold water, enhancing its water absorption and swelling capacity. This enhanced water absorption facilitates rapid disintegration of the capsules in vivo, increasing the drug release rate. Further comparing Examples 1, 4, and 6, the hollow capsules prepared from modified hydroxypropyl starch exhibited better disintegration properties and lower friability. The addition of lactic acid and carboxymethyl cellulose improved the water absorption and swelling properties of hydroxypropyl starch, which facilitated rapid water absorption and swelling of the capsules in vivo, thereby increasing the disintegration rate. Furthermore, carboxymethyl cellulose, as a water-soluble polymer, rapidly absorbs water and swells, promoting rapid disintegration of the capsule wall and thus increasing the disintegration rate. Simultaneously, the addition of carboxymethyl cellulose also improved the flexibility and rupture resistance of the capsule wall, further reducing friability. The addition of lactic acid allowed for esterification with hydroxypropyl starch, forming a more stable network structure, increasing the mechanical strength of the capsule wall, and reducing friability.

[0108] In summary, using lactic acid and carboxymethyl cellulose-modified hydroxypropyl starch as the raw material for empty capsules can improve the overall performance of the capsules by enhancing hydrophilicity, increasing mechanical strength, optimizing disintegration performance, and improving water absorption and swelling properties, thereby achieving a higher disintegration rate and lower brittleness compared to pregelatinized hydroxypropyl starch.

Claims

1. A hydroxypropyl starch empty capsule, comprising 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; The pigment is iron oxide red; The preparation process of the modified hydroxypropyl starch includes the following steps: N1 Take 20 parts by weight of corn starch and add it to 80 parts by weight of purified water. Stir well to obtain starch emulsion. Then add 4 wt% of the starch weight of swelling agent. Heat the mixture at 90°C for 2 hours. Cool to room temperature, filter and wash to obtain pre-swollen starch. The swelling agent is sodium hydroxide. N2 mixes all of the above pre-swollen starch, 80 parts by weight of purified water and 2 parts by weight of propylene oxide, adjusts the pH to 11.5 with 2 mol / L sodium hydroxide aqueous solution, heats the reaction at 40°C for 16 h, cools to room temperature, neutralizes the system with 1 mol / L hydrochloric acid until the system is neutral, filters, washes and dries to obtain hydroxypropyl starch. N3 mixed all of the above hydroxypropyl starch with 60 parts by weight of purified water and stirred at 75°C and 400 rpm for 45 min to obtain gelatinized hydroxypropyl starch. 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 were added to the above gelatinized hydroxypropyl starch. The pH was adjusted to 6, and the mixture was stirred at 55°C and 400 rpm for 1.5 hours. After cooling to room temperature, the starch was washed, filtered, and dried to obtain modified hydroxypropyl starch. The amylase activity was 200,000 U / g. The method for preparing the hydroxypropyl starch empty capsules includes the following steps: S1 Weigh each raw material according to the weight parts; S2 heated purified water to 78°C, added modified hydroxypropyl starch, stirred at 600 rpm for 25 min, added carrageenan and continued stirring for 15 min, then added potassium chloride, pullulan, glycerol and nano titanium dioxide and continued stirring for 30 min, and gelled at 70°C for 5 h to obtain sol. S3 dips the above sol into the sol at 40°C to form a shape, dries it, places it at room temperature for 0.5 hours, and finally demolds it. After passing quality inspection, it is cut and assembled to obtain hydroxypropyl starch hollow capsules.

Images