Use of a gel composition for the preparation of soft vegetable capsules for pharmaceutical use

Abstract

The application discloses application of a gel composition in preparation of a medical pressed plant source soft capsule, and the gel composition is composed of a gelling agent and a gelling accelerator, wherein the gelling agent is composed of agar and carrageenan, the carrageenan is kappa-carrageenan and / or iota-carrageenan, and the gelling accelerator is composed of a soluble potassium salt and a soluble sodium salt. The medical pressed plant source soft capsule prepared by the application can avoid problems of a gelatin soft capsule, avoid safety hazards of the gelatin, and improve stability and safety of the plant soft capsule, and therefore has good application value in the medical industry and the health product industry.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, specifically relating to the application of gel compositions in the preparation of medical compressed plant-derived soft capsules. Background Technology

[0002] Capsules are a traditional oral dosage form, used to encapsulate poorly soluble drugs, mask unpleasant odors, and improve drug bioavailability. Unlike hard capsules, soft capsules are generally used to encapsulate liquid drugs. Solid drugs can be prepared as solutions or semi-solids and then encapsulated into spherical or elliptical soft capsules. Currently, most capsules on the market are gelatin-based, with plant-derived soft capsules accounting for a small percentage. Due to its molecular structure, gelatin soft capsules have several drawbacks. These include hygroscopicity leading to drug deterioration, susceptibility to cross-linking and solidification reactions with various drugs, prolonged disintegration time, and reduced drug bioavailability. The U.S. Food and Drug Administration (FDA) believes gelatin should be removed from its list of basically safe drugs. Therefore, there is an urgent need to find new capsule formulations to replace gelatin soft capsules.

[0003] With changing consumer attitudes towards health and increased regulatory oversight of pharmaceutical companies, plant-based soft capsules are gradually becoming a market trend. Plant-based soft capsules can overcome many of the drawbacks of gelatin soft capsules while retaining some of their advantages. They offer higher stability and safety, do not undergo cross-linking reactions with drugs, and effectively improve bioavailability and shelf life. However, the technology for plant-based soft capsules is still not mature, and the mechanical properties of the prepared soft capsules still lag behind those of gelatin soft capsules. Therefore, developing plant-based soft capsules with excellent mechanical properties and rapid disintegration by adding blending gelling agents and coagulants has significant practical implications for the high-value utilization of marine resources and high-quality discovery in the pharmaceutical industry. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of the prior art and provide the application of gel composition in the preparation of medical compressed plant-derived soft capsules.

[0005] The technical solution of the present invention is as follows:

[0006] The application of the gel composition in the preparation of medical compressed plant-derived soft capsules is characterized in that: the gel composition comprises a gelling agent and a coagulating accelerator, wherein,

[0007] The gelling agent consists of agar and carrageenan, with carrageenan being... κ - Carrageenan and / or ι - Carrageenan, and the mass of carrageenan is greater than the mass of agar.

[0008] The coagulant is composed of soluble potassium salt and soluble sodium salt.

[0009] In a preferred embodiment of the invention, the gelling agent is composed of agar and κ-carrageenan in a mass ratio of 1:10.

[0010] In a preferred embodiment of the invention, the gelling agent is composed of agar and 1-carrageenan in a mass ratio of 1:10.

[0011] In a preferred embodiment of the invention, the gelling agent is composed of agar, κ-carrageenan and ι-carrageenan in a mass ratio of 0.5-1.5:4-10:1.

[0012] In a preferred embodiment of the present invention, the soluble potassium salt is potassium citrate and the soluble sodium salt is sodium chloride.

[0013] More preferably, the mass ratio of potassium citrate to sodium chloride is 1-4:1-4.

[0014] In a preferred embodiment of the present invention, the mass ratio of the gelling agent to the coagulant is 11-12.5:3.

[0015] In a preferred embodiment of the present invention, the raw materials of the medical compressed plant-derived soft capsules further include plant-derived film-forming agents and glycerin.

[0016] More preferably, the plant-derived film-forming agent is pullulan, hydroxypropyl methylcellulose, or carboxymethyl starch.

[0017] More preferably, the mass ratio of the gelling agent, coagulant, plant-derived film-forming agent and glycerin is 11-12.5:3:60:60.

[0018] The beneficial effects of this invention are:

[0019] 1. The gel composition of the present invention can be used to prepare plant soft capsules with different film-forming agents and plasticizers, and produce plant soft capsules of different materials.

[0020] 2. The medical compressed plant-derived soft capsules prepared by this invention have the characteristic of rapid disintegration in hydrochloric acid solution with pH=1.2, which can improve the bioavailability of the capsules;

[0021] 3. The gel composition in this invention can regulate the mechanical properties of special membrane materials, solving the problems of poor mechanical strength and easy brittleness of plant soft capsules;

[0022] 4. The combination of soluble potassium salt and soluble sodium salt in the gel composition of the present invention can regulate the disintegration performance of the special membrane material, thus solving the problems of long disintegration time and slow dissolution rate of plant soft capsules.

[0023] 5. The medical-grade compressed plant-derived soft capsules prepared by this invention can avoid the problems and safety hazards of gelatin soft capsules, and improve the stability and safety of plant-derived soft capsules. This invention has good application value for the pharmaceutical and health product industries. Detailed Implementation

[0024] The technical solution of the present invention will be further explained and described below through specific embodiments.

[0025] Comparative Examples 1 to 3

[0026] The allocation of comparative examples 1 to 3 is shown in Table 1:

[0027] Table 1

[0028]

[0029] Preparation methods of Comparative Examples 1-3:

[0030] (1) Add water to a vacuum gelling tank and heat to 90°C. Add gelling agent (agar, κ-carrageenan, and / or ι-carrageenan), and stir until completely dissolved. Add the remaining components and stir for 2 hours to fully dissolve the raw materials. Cool to 85°C and maintain the temperature for 18 hours to obtain a clear and transparent gel solution with a viscosity of 17000-21000 mPa·s.

[0031] (2) The gelatinous solution prepared in step (1) is fed into a pelletizing machine for pelletizing. After shaping and drying, medical-grade pressed plant-derived soft capsules are obtained. Among them:

[0032] The operating parameters for the pelleting process are as follows: pelleting machine spray temperature is 85℃, glue box temperature is 90℃, water cooler temperature is 15℃, rolling speed is 2rpm, and glue thickness is 1mm; the operating parameters for the drying process are as follows: the ambient temperature is controlled at 32℃, the relative humidity is 45%, and the drying time is 2h, then the ambient temperature is increased to 45℃, the relative humidity is 45%, and the drying time is 20h, resulting in medical-grade pressed plant-derived soft capsules.

[0033] (3) The medical pressed plant-derived soft capsules obtained in step (2) are inspected with a light inspection table to remove soft capsules that do not meet the quality requirements, such as those with bubbles, deformities, leakage, or bulging. The qualified pullulan polysaccharide plant soft capsules are collected and sealed for preservation.

[0034] (4) The mechanical properties, moisture content, disintegration time, and friability of the medical compressed plant-derived soft capsules were measured, and the results are shown in Table 2:

[0035] Table 2

[0036]

[0037]

[0038] The results of Comparative Examples 1 to 3 show that blended gelling agents can compensate for the shortcomings of single gelling agents.

[0039] Examples 1 to 7

[0040] The allocation examples for groups 1-7 in Examples are shown in Table 3.

[0041] Table 3

[0042]

[0043] Preparation methods of Examples 1 to 7:

[0044] (1) Add water to a vacuum gelling tank and heat to 85°C. Add gelling agent (agar, κ-carrageenan, and / or ι-carrageenan), and stir until completely dissolved. Add the remaining components and stir for 2 hours to fully dissolve the raw materials. Cool to 75°C and maintain the temperature for 16 hours to obtain a clear and transparent gel solution with a viscosity of 14000-18000 mPa·s.

[0045] (2) The gelatin solution prepared in step (1) is transported to a pelletizing machine for pelleting. After shaping and drying, medical-grade pressed plant-derived soft capsules are obtained. The operating parameters of the pelletizing process are as follows: the temperature of the pelletizing machine spray is 80℃, the temperature of the gel box is 85℃, the temperature of the water cooler is 18℃, the rolling speed is 1.5 rpm, and the thickness of the gel is 1.1-1.3 mm. The operating parameters of the drying process are as follows: the ambient temperature is controlled at 35℃, the relative humidity is 35%, and the drying time is 2 hours. Then, the ambient temperature is increased to 50℃, the relative humidity is 35%, and the drying time is 18 hours to obtain medical-grade pressed plant-derived soft capsules.

[0046] (3) The medical pressed plant-derived soft capsules obtained in step (2) are inspected with a light inspection table to remove soft capsules that do not meet the quality requirements, such as those with bubbles, deformities, leakage, or bulging. The qualified pullulan polysaccharide plant soft capsules are collected and sealed for preservation.

[0047] (4) The mechanical properties, moisture content, disintegration time and friability of the medical compressed plant-derived soft capsule samples were measured, and the results are shown in Table 4.

[0048] Table 4

[0049] serial number Elongation at break (%) Tensile strength (MPa) Moisture content (%) Disintegration timeout (min) Crispness (particle size) Example 1 273 2.3 16.6 23 18 Example 2 172 5.6 12.6 27 3 Example 3 208 3.3 14.4 21 1 Example 4 227 3.7 14.9 19 0 Example 5 218 3.2 15.7 18 0 Example 6 197 4.1 10.5 15 3 Example 7 215 3.4 14.3 21 2

[0050] The above results indicate that agar and carrageenan have good compatibility, and their single helices can form an agar-carrageenan double helix structure, improving the compactness of the polysaccharide network structure and thus enhancing the tensile strength and elongation at break of medical compressed plant-derived soft capsules. Therefore, adding agar to the κ-carrageenan / ι-carrageenan binary plant capsule system can improve capsule performance; the disintegration time of the prepared samples was <1 h, meeting the requirements of the Chinese Pharmacopoeia.

[0051] Comparative Examples 4 to 5 and Examples 8 to 9

[0052] The component ratios of Comparative Examples 4 to 5 and Examples 8 to 9 are shown in Table 5:

[0053] Table 5

[0054]

[0055] Preparation methods of Comparative Examples 4 and 5 and Examples 8 and 9:

[0056] (1) Add water to a vacuum gelling tank and heat to 85°C. Add gelling agent (agar, κ-carrageenan, and / or ι-carrageenan), and stir until completely dissolved. Add the remaining components and stir for 2 hours to fully dissolve the raw materials. Cool to 80°C and maintain the temperature for 12 hours to obtain a clear and transparent gel solution with a viscosity of 16000-19000 mPa·s.

[0057] (2) The gelatin solution prepared in step (1) is transported to a pelletizing machine for pelleting. After shaping and drying, medical-grade pressed plant-derived soft capsules are obtained. The operating parameters of the pelletizing process are as follows: the temperature of the pelletizing machine spray is 82℃, the temperature of the gel box is 87℃, the temperature of the water cooler is 20℃, the rolling speed is 1.5 rpm, and the thickness of the gel is 0.9 mm. The operating parameters of the drying process are as follows: the ambient temperature is controlled at 25℃, the relative humidity is 40%, and the drying time is 2 hours. Then, the ambient temperature is increased to 40℃, the relative humidity is 25%, and the drying time is 16 hours to obtain medical-grade pressed plant-derived soft capsules.

[0058] (3) The medical pressed plant-derived soft capsules obtained in step (2) are inspected with a light inspection table to remove soft capsules that do not meet the quality requirements, such as those with bubbles, deformities, leakage, or bulging. The qualified pullulan polysaccharide plant soft capsules are collected and sealed for preservation.

[0059] (4) The mechanical properties, moisture content, disintegration time and friability of the medical compressed plant-derived soft capsule samples were measured, and the results are shown in Table 6.

[0060] Table 6

[0061] serial number Elongation at break (%) Tensile strength (MPa) Moisture content (%) Disintegration timeout (min) Crispness (particle size) Comparative Example 4 178 4.2 12.1 24 4 Comparative Example 5 236 2.7 15.5 16 9 Example 8 221 3.4 15.1 20 0 Example 9 241 2.9 14.9 18 2

[0062] Experimental results show that ions have a significant impact on blended gelling agents, and a single ion may not be able to meet the response requirements of diverse gelling agents. Blending ions can improve the mechanical properties of blended gelling agent soft capsules, compensating for the low responsiveness of single ions. The disintegration time of all prepared samples was <1 h, meeting the requirements of the Chinese Pharmacopoeia.

[0063] Single gelling agents cannot meet diverse needs due to their inherent properties. For example, while single κ-carrageenan gel has high rigidity, it lacks flexibility; single ι-carrageenan gel has high softness but insufficient rigidity; and single agar gel has high strength but is brittle. Therefore, composite gelling agents can be used to overcome the shortcomings of single gelling agents.

[0064] While binary gelling agents composed of κ-carrageenan and ι-carrageenan can produce plant-based soft capsules with good tensile strength and elongation at break through blending, the addition of large amounts of carrageenan leads to high viscosity and gelation temperature in the soft capsule solution. This presents significant challenges in the production process. For example, air bubbles are difficult to remove during the defoaming process, resulting in high energy consumption and prolonged production cycles; the high spray temperature during production also affects the encapsulation efficiency of the soft capsules. Therefore, it is necessary to reduce the viscosity of the κ-carrageenan / ι-carrageenan binary system.

[0065] Agar has a lower viscosity than both types of carrageenan, and because agar shares a similar molecular structure with κ-carrageenan and ι-carrageenan, agar and carrageenan molecules can first form a single helix in solution and then a double helix structure, exhibiting good compatibility. Adding agar to the κ-carrageenan / ι-carrageenan binary system can reduce the viscosity of the binary system. Without adding other components, adding agar at 80℃ can reduce the viscosity of the binary system from 600 mPa·s to 300-400 mPa·s, indicating that adding agar can effectively reduce the viscosity of the binary system. Since agar itself has good gelling properties and good compatibility with carrageenan, adding agar can improve the mechanical properties and stability of binary plant-based soft capsules.

[0066] The above description is merely a preferred embodiment of the present invention, and therefore should not be construed as limiting the scope of the present invention. All equivalent changes and modifications made in accordance with the scope of the patent and the contents of the specification should still fall within the scope of the present invention.

Claims

1. Use of a gel composition for the preparation of a soft medicinal plant-based capsule under pressure, characterized in that: The gel composition is composed of a gelling agent and a coagulant in a mass ratio of 11-12.5:3, wherein, The gelling agent is composed of agar and carrageenan, the carrageenan is κ-carrageenan and / or ι-carrageenan, and the mass of the carrageenan is greater than the mass of the agar, specifically, composed of agar and κ-carrageenan in a mass ratio of 1:10, or composed of agar and ι-carrageenan in a mass ratio of 1:10, or composed of agar, κ-carrageenan and ι-carrageenan in a mass ratio of 0.5-1.5:4-10:1; The coagulant is composed of potassium citrate and sodium chloride in a mass ratio of 1-4:1-4.

2. Use according to claim 1, characterized in that: The raw material of the medical pressed plant source soft capsule further comprises a plant source film forming agent and glycerol.

3. Use according to claim 2, wherein: The plant source film forming agent is pullulan, hypromellose or carboxymethyl starch.

4. Use according to claim 3, characterized in that: The mass ratio of the gelling agent, the coagulant, the plant source film forming agent and the glycerol is 11-12.5:3:60:60.

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