Empty capsule formula and preparation method thereof

Abstract

The invention discloses an empty capsule formula and a preparation method thereof, and belongs to the field of biological medicine manufacturing, and the empty capsule formula comprises the following components by weight: 20-50 parts of a membrane material; 1-15 parts of a chelating agent; 1 to 20 parts of colloidal silicon dioxide; 0.1 to 13 parts of a surfactant; 1 to 15 parts of gel; the invention also discloses a preparation method of the empty capsule. According to the invention, the colloidal silicon dioxide is added, so that the produced hollow capsules made of different materials have the characteristic of quick dissolution, and the requirements of capsule preparations with strict control on the dissolution rate can be met; according to the empty capsule formula, the dissolution property can be kept stable under four PH conditions (PH is 1.2, PH is 4.0, PH is 6.8 and water), and the dissolution rate is close to the dissolution rate of a gelatin empty capsule formula within the time period of 300-60 min.

Description

Technical Field

[0001] The invention relates to the field of biomedicine manufacturing, and in particular to a hollow capsule formula and a preparation method thereof. Background Art

[0002] In recent years, with the development and listing of plant hollow capsules, on the one hand, plant-derived materials reduce the risk of animal-derived materials, and the low moisture content of plant materials is not brittle, and the characteristics of good stability avoid the problem of cross-linking reaction and brittle risk of similar gelatin hollow capsules, so that plant hollow capsules have received more and more attention. The hollow capsule prescription obtained by plant membrane materials on the market is relatively complicated, and some gelling agents need to be added, such as gum arabic, carrageenan (alginate), xanthan gum, gellan gum, konjac gum, agar, locust bean gum, sodium alginate, konjac mannan, etc., so that the hollow capsule shell will dissolve and slow down. In addition, the existing hollow capsule cannot reach the technical effect of dissolution properties and gelatin, so that the hollow capsule application range of plant-derived materials is limited, and it is impossible to be applied in the capsule preparation with strict requirements on dissolution. Summary of the invention

[0003] Technical problem to be solved: In view of the problems existing in the prior art, the present invention provides a hollow capsule and a preparation method thereof, which can maintain stable dissolution properties under four pH conditions (pH 1.2, pH 4.0, pH 6.8 and water) and has a hollow capsule close to that of gelatin.

[0004] Technical solution: The hollow capsule formula of the present invention comprises the following components by weight: 20~50 parts of membrane material; 1-15 parts of chelating agent; 1-20 parts of colloidal silicon dioxide; Surfactant 0.1~13 parts; 1~15 parts of gelling agent; 100 parts of water.

[0005] Preferably, the membrane material is one of HPMC, pullulan, starch and carboxymethyl chitosan.

[0006] Preferably, the chelating agent is one or a combination of anhydrous citric acid, sodium citrate, potassium citrate, sodium malate, potassium acetate, ethylenediaminetetraacetic acid (EDTA), and phytic acid.

[0007] Preferably, the surfactant is one or a combination of sodium lauryl sulfate, poloxamer, Tween 80, Span 20, sucrose fatty acid ester, sucrose monolaurate, sucrose palmitate, and glycerol fatty acid ester.

[0008] Preferably, the gelling agent is one or a combination of xanthan gum, gellan gum, carrageenan, gum arabic, konjac gum, agar, locust bean gum, sodium alginate, and konjac mannan.

[0009] Preferably, the water is purified water or distilled water.

[0010] The present invention also discloses a method for preparing a hollow capsule, comprising the following steps: Step 1: Weigh the corresponding amount of gelling agent and add it into water heated to 80-90°C to dissolve; Step 2: After the gelling agent is completely dissolved, add the weighed colloidal silica and surfactant, and stir and mix at a stirring speed of 600-1400 rpm for 8-10 minutes; Step 3: Add a proportion of membrane material to the mixed solution and stir thoroughly until it is completely dispersed and dissolved; Step 4: Add a proportion of chelating agent and stir evenly at a stirring speed of 500-800 rpm; Step 5: injecting the mixed raw materials into a capsule mold of the required size to prepare a hollow capsule; Step 6: After the capsules are completely dry, perform the dissolution test.

[0011] Preferably, the specific steps of step 3 are: Step 31: stirring at a stirring speed of 750-4500 rpm for 40-60 min, cooling the glue solution to 25-35°C; Step 32: Heat the stirred glue solution to 40-50°C, stir evenly after the temperature reaches the preset insulation temperature, and let it stand for 45-100 minutes after stirring.

[0012] Compared with the prior art, the present invention has at least the following beneficial effects: 1. The addition of colloidal silicon dioxide in the present invention can make the hollow capsules of different materials have the characteristic of rapid dissolution, and can meet the requirements of capsule preparations with strict control of dissolution; the hollow capsule formula can maintain stable dissolution properties under four pH conditions (PH1.2, PH4.0, PH6.8 and water), and the dissolution rate in the time period of 300-60 minutes is close to that of the gelatin hollow capsule formula; 2. The hollow capsule formula makes the capsules more transparent in appearance, which is comparable to gelatin capsules in appearance. The formula expands the application range of hollow capsules. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 It is a schematic diagram of the preparation process structure of the hollow capsule of the present invention. DETAILED DESCRIPTION

[0014] In order to make the purpose, technical solution and advantages of the embodiment of the present invention clearer, the technical solution of the embodiment of the present invention is clearly and completely described below. Obviously, the described embodiment is a part of the embodiment of the present invention, not all the embodiments. Based on the described embodiment of the present invention, all other embodiments obtained by ordinary technicians in this field belong to the scope of protection of the present invention.

[0015] The hollow capsule formula of the present invention comprises the following components by weight: 20-50 parts of membrane material, wherein the membrane material is one of HPMC, pullulan, starch and carboxymethyl chitosan; 1-15 parts of a chelating agent, wherein the chelating agent is one or a combination of anhydrous citric acid, sodium citrate, potassium citrate, sodium malate, potassium acetate, ethylenediaminetetraacetic acid EDTA, and phytic acid; 1-20 parts of colloidal silicon dioxide; 0.1-13 parts of surfactant, wherein the surfactant is one or a combination of sodium lauryl sulfate, poloxamer, Tween 80, Span 20, sucrose fatty acid ester, sucrose monolaurate, sucrose palmitate, and glycerol fatty acid ester; 1-15 parts of a gelling agent, wherein the gelling agent is one or a combination of xanthan gum, gellan gum, carrageenan, gum arabic, konjac gum, agar, locust bean gum, sodium alginate, and konjac mannan; 100 parts of water, the water is purified water or distilled water.

[0016] like Figure 1 As shown, the present invention also discloses a method for preparing a hollow capsule, comprising the following steps: Step 1: Weigh the corresponding amount of gelling agent and add it into water heated to 80-90°C to dissolve; Step 2: After the gelling agent is completely dissolved, add the weighed colloidal silica and surfactant, and stir and mix at a stirring speed of 600-1400 rpm for 8-10 minutes; Step 3: Add a proportion of membrane material to the mixed solution, stir for 40-60 minutes at a stirring speed of 750-4500 rpm, and cool the glue solution to 25-35°C; then heat the stirred glue solution to 40-50°C, and stir until the temperature reaches the preset insulation temperature until it is completely dispersed and dissolved, and let it stand for 45-100 minutes after stirring. Step 4: Add a proportion of chelating agent and stir evenly at a stirring speed of 500-800 rpm; Step 5: injecting the mixed raw materials into a capsule mold of the required size to prepare a hollow capsule; Step 6: After the capsules are completely dry, perform the dissolution test.

[0017] Embodiment 1: A hollow capsule formula of the present invention comprises the following components by weight: HPMC 35 parts, anhydrous citric acid 10 parts, colloidal silicon dioxide 10 parts, sodium lauryl sulfate 5 parts, carrageenan 10 parts, purified water 100 parts.

[0018] Embodiment 2: A hollow capsule formula of the present invention comprises the following components by weight: 30 parts of pullulan, 11 parts of sodium citrate, 13 parts of colloidal silicon dioxide, 8 parts of poloxamer, 10 parts of gellan gum, and 100 parts of purified water.

[0019] Embodiment 3: A hollow capsule formula of the present invention comprises the following components by weight: HPMC 40 parts, potassium citrate 7 parts, colloidal silicon dioxide 13 parts, Tween 80 9 parts, gum arabic 10 parts, distilled water 100 parts.

[0020] Embodiment 4: The present invention also discloses a method for preparing a hollow capsule, comprising the following steps: (1) Weigh the corresponding amount of gelling agent and add it into water heated to 85℃ to dissolve.

[0021] (2) After the gelling agent is completely dissolved, add the weighed colloidal silica and surfactant, and stir at a stirring speed of 1000 rpm for 10 minutes.

[0022] (3) Add a proportion of membrane material to the mixed solution, stir at a stirring speed of 2000 rpm for 60 min, and cool the glue solution to 35°C; then raise the temperature of the stirred glue solution to 40°C, wait until the temperature reaches the preset insulation temperature, and stir it thoroughly until it is completely dispersed and dissolved. After stirring, let it stand for 45 min.

[0023] (4) Add a proportion of chelating agent and stir evenly at a stirring speed of 500 rpm.

[0024] (5) The mixed raw materials are injected into a capsule mold of the required size to prepare hollow capsules.

[0025] (6) After the capsules are completely dry, perform a dissolution test.

[0026] Embodiment 5: The present invention also discloses a method for preparing a hollow capsule, comprising the following steps: (1) Weigh the corresponding amount of gelling agent and add it into water heated to 90℃ to dissolve.

[0027] (2) After the gelling agent is completely dissolved, add the weighed colloidal silica and surfactant, and stir at a stirring speed of 600 rpm for 8 minutes.

[0028] (3) Add a proportion of membrane material to the mixed solution, stir at a stirring speed of 750 rpm for 50 min, and cool the glue solution to 35°C; then heat the stirred glue solution to 45°C, wait until the temperature reaches the preset insulation temperature, and stir it thoroughly until it is completely dispersed and dissolved. After stirring, let it stand for 90 min.

[0029] (4) Add a proportion of chelating agent and stir evenly at a stirring speed of 500 rpm.

[0030] (5) The mixed raw materials are injected into a capsule mold of the required size to prepare hollow capsules.

[0031] (6) After the capsules are completely dry, perform a dissolution test.

[0032] Embodiment 6: The present invention also discloses a method for preparing a hollow capsule, comprising the following steps: (1) Weigh the corresponding amount of gelling agent and add it into water heated to 80℃ to dissolve.

[0033] (2) After the gelling agent is completely dissolved, add the weighed colloidal silica and surfactant, and stir at a stirring speed of 1400 rpm for 10 minutes.

[0034] (3) Add a proportion of membrane material to the mixed solution, stir at a stirring speed of 4500 rpm for 40 min, and cool the glue solution to 25°C; then heat the stirred glue solution to 50°C, wait until the temperature reaches the preset insulation temperature, and stir it thoroughly until it is completely dispersed and dissolved. After stirring, let it stand for 100 min.

[0035] (4) Add a proportion of chelating agent and stir evenly at a stirring speed of 800 rpm.

[0036] (5) The mixed raw materials are injected into a capsule mold of the required size to prepare hollow capsules.

[0037] (6) After the capsules are completely dry, perform a dissolution test.

[0038] The dissolution test data of the hollow capsules prepared by the hollow capsule formulas of Examples 1 to 3 of the present invention (Examples), the hydroxypropyl methylcellulose hollow capsules without adding colloidal silicon dioxide (Comparative Example 1), and the clear gelatin capsules (Comparative Example 2) under different pH conditions are shown in Table 1.

[0039] Table 1 Dissolution of the hollow capsules of Examples and Comparative Examples 1-2 under different pH conditions (%): .

[0040] As shown in Table 1, the addition of colloidal silicon dioxide in the present invention can make the hollow capsules of different materials have the characteristics of rapid dissolution, and can meet the requirements of capsule preparations with strict control of dissolution; the hollow capsule formula of the present invention can maintain stable dissolution properties under four pH conditions (PH1.2, PH4.0, PH6.8 and water), and the dissolution rate in the time period of 300-60min is close to that of the hollow gelatin capsule formula. The hollow capsule formula of the present invention has a relatively transparent appearance, and its appearance can be comparable to that of gelatin capsules, and the formula expands the application range of hollow capsules.

[0041] The permeability test data of the hollow capsules prepared by the hollow capsule formulas of Examples 1 to 3 of the present invention (Examples), the hypromellose hollow capsules without adding colloidal silicon dioxide (Comparative Example 1), and the clear gel capsules (Comparative Example 2) are shown in Table 2.

[0042] Table 2 Transmission rate of hollow capsules of Examples and Comparative Examples 1-2 (%): .

[0043] As can be seen from Table 2, the hollow capsules prepared by the formula of the embodiment of the present invention have higher permeability than the hollow capsules of hydroxypropyl methylcellulose without adding colloidal silicon dioxide (Comparative Example 1) and the hollow capsules of Mingjiao (Comparative Example 2), which is conducive to the efficient dissolution of the capsule preparation.

[0044] The above are preferred embodiments of the present invention. It should be pointed out that, for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A hollow capsule formula, characterized in that: The hollow capsule formula includes the following weight components: 20~50 parts of membrane material; 1-15 parts of chelating agent; 1-20 parts of colloidal silicon dioxide; Surfactant 0.1~13 parts; 1~15 parts of gelling agent; 100 parts water.

2. The hollow capsule formulation according to claim 1, characterized in that: The membrane material is one of HPMC, pullulan, starch and carboxymethyl chitosan.

3. The hollow capsule formulation according to claim 1, characterized in that: The chelating agent is one or a combination of anhydrous citric acid, sodium citrate, potassium citrate, sodium malate, potassium acetate, ethylenediaminetetraacetic acid EDTA, and phytic acid.

4. The hollow capsule formulation according to claim 1, characterized in that: The surfactant is one or a combination of sodium lauryl sulfate, poloxamer, Tween 80, Span 20, sucrose fatty acid ester, sucrose monolaurate, sucrose palmitate, and glycerol fatty acid ester.

5. The hollow capsule formulation according to claim 1, characterized in that: The gelling agent is one or a combination of xanthan gum, gellan gum, carrageenan, gum arabic, konjac gum, agar, locust bean gum, sodium alginate and konjac mannan.

6. The hollow capsule formulation according to claim 1, characterized in that: The water is purified water or distilled water.

7. A method for preparing a hollow capsule, characterized in that: The method for preparing any one of claims 1 to 6 hollow capsules comprises the following steps: Step 1: Weigh the corresponding amount of gelling agent and add it into water heated to 80-90°C to dissolve; Step 2: After the gelling agent is completely dissolved, add the weighed colloidal silica and surfactant, and stir and mix at a stirring speed of 600-1400 rpm for 8-10 minutes; Step 3: Add a proportion of membrane material to the mixed solution and stir thoroughly until it is completely dispersed and dissolved; Step 4: Add a proportion of chelating agent and stir evenly at a stirring speed of 500-800 rpm; Step 5: injecting the mixed raw materials into a capsule mold of the required size to prepare a hollow capsule; Step 6: After the capsules are completely dry, perform the dissolution test.

8. The method for preparing hollow capsules according to claim 7, characterized in that: The specific steps of step 3 are: Step 31: stirring at a stirring speed of 750-4500 rpm for 40-60 min, cooling the glue solution to 25-35°C; Step 32: Heat the stirred glue solution to 40-50°C, stir evenly after the temperature reaches the preset insulation temperature, and let it stand for 45-100 minutes after stirring.

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