Gelatin hollow capsule and its preparation method and application

Abstract

The present application provides a gelatin hollow capsule and a preparation method and application thereof, and relates to the technical field of capsule preparation. The gelatin hollow capsule comprises, by weight fraction, 2400-2600 parts of purified water, 900-1000 parts of acid method gelatin, 80-120 parts of pectin, 5-10 parts of beta-cyclodextrin, 1-5 parts of DL-sodium malate, 15-40 parts of glacial acetic acid and 12-15 parts of titanium dioxide. The hollow capsule provided by the present application is modified by introducing beta-cyclodextrin and DL-sodium malate, so that the anti-fracture brittleness and moisturizing effect of the hollow capsule are improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of capsule preparation, in particular to a gelatin hollow capsule and a preparation method and application thereof. BACKGROUND

[0002] Gelatin capsules are affected by environmental humidity during storage and transportation, which may cause problems such as moisture absorption of drug powder into columns and brittle cracking of capsules. This is because the gelatin molecules in the gelatin capsule mainly form a triple helix structure. When the capsule prepared by drying this system in an environment with a water content of less than 10%, the capsule is prone to brittle cracking. When the environmental humidity is high, the drug powder is prone to moisture absorption into columns, resulting in a shortened product shelf life and unqualified quality. Therefore, it is of great significance to improve the mechanical properties and water retention of gelatin hard capsules for improving the application of gelatin as a capsule auxiliary material.

[0003] Under the conditions of the prior art, plasticizers and humectants are generally introduced to improve the brittle performance of gelatin capsules. For example, the commonly used plasticizer PEG slightly improves the brittle performance of the capsule due to its good compatibility with gelatin. The selection and optimization of raw materials are also key factors affecting the capsule friability. In the article "Progress of polysaccharide-protein composite hydrogel", it is pointed out that a small amount of pectin (crystalline network structure, good flexibility) molecules mixed with gelatin molecules can improve the mechanical strength of the film material. Chinese Patent Publication No. CN114732793A discloses a hollow capsule and a preparation method thereof. In this patent, zinc oxide is used as a light shielding agent to improve the protection of light-sensitive drugs by the capsule, but the capsule does not improve the brittle cracking and moisture retention. Therefore, in order to solve the brittle cracking problem of gelatin capsules, there is an urgent need for a preparation method of a brittle cracking prevention and moisture retention gelatin hollow capsule that is mature in process, simple to prepare, and high in safety.

[0004] It should be noted that the information disclosed in the above background section is only used to strengthen the understanding of the background of the present disclosure, and therefore can include information that does not constitute prior art known to those of ordinary skill in the art. SUMMARY

[0005] Therefore, the present application provides a gelatin hollow capsule and a preparation method and application thereof, which improve the brittle cracking resistance and moisture retention effect of the gelatin hollow capsule by adding an additive.

[0006] The technical scheme of the present application is as follows:

[0007] The present application provides a gelatin hollow capsule, which comprises, by weight, 2400-2600 parts of purified water, 900-1000 parts of acid gelatin, 80-120 parts of pectin, 5-10 parts of beta-cyclodextrin, 1-5 parts of DL-sodium malate, 15-40 parts of glacial acetic acid, and 12-15 parts of titanium dioxide.

[0008] Preferably, the mass ratio of the beta-cyclodextrin to the sodium DL-malate is 8:2 by weight.

[0009] Preferably, the acid gelatin is at least one of acid bone gelatin and acid skin gelatin.

[0010] The application further provides a preparation method of the gelatin hollow capsule.

[0011] S10, adding the acid gelatin into purified water at 60-75°C, and stirring at 600-900 r / min for 10-20 min to obtain a gelatin glue solution;

[0012] S20, adding the pectin and the sodium DL-malate into the gelatin glue solution, heating to 80-85°C, and stirring at 600-900 r / min for 25-35 min to obtain a first mixed glue solution;

[0013] S30, obtaining a beta-cyclodextrin water solution, adding the beta-cyclodextrin water solution into the first mixed glue solution in step S20, and stirring at 600-900 r / min for 50-75 min in a 50-60°C water bath to obtain a second mixed glue solution;

[0014] S40, adjusting the pH value of the second mixed glue solution to be acidic to obtain a capsule precursor solution; and sequentially performing glue nourishing, blank making, drying, and assembling on the capsule precursor solution to obtain the gelatin hollow capsule.

[0015] Preferably, in step S40, glacial acetic acid is used to adjust the pH value of the capsule precursor solution to 5.2-5.7.

[0016] Preferably, in step S30, the obtaining of the beta-cyclodextrin water solution comprises mixing the beta-cyclodextrin with purified water.

[0017] Preferably, the mass ratio of the beta-cyclodextrin to the purified water is 1:(16-22).

[0018] The temperature of the purified water is 50-70°C.

[0019] Preferably, in step S40, the glue nourishing comprises placing the capsule precursor solution at a temperature of 45-65°C and keeping still for at least 5 h.

[0020] Preferably, in step S40, the drying comprises drying the shaped capsule obtained by the blank making at a relative humidity of 58%-60% and a temperature of 20-30°C for 70-90 min.

[0021] On the basis of the above technical scheme, preferably, in the step S40, before the gelatin is maintained, the capsule precursor liquid further comprises adding titanium dioxide for color adjustment.

[0022] The application further provides application of the above gelatin hollow capsule in preparation of capsule.

[0023] The gelatin hollow capsule and the preparation method thereof have the following beneficial effects compared with the prior art:

[0024] 1. By adding pectin as a compound base material, the pectin and acid gelatin are combined to improve the toughness and elasticity of the gelatin hollow capsule and improve the anti-fracture brittleness of the gelatin hollow capsule.

[0025] 2. The gelatin hollow capsule provided by the disclosure adds β-cyclodextrin as a plasticizing aid and DL-sodium malate as a moisturizing aid, which synergistically improves the anti-fracture brittleness of the gelatin hollow capsule and improves the moisturizing effect of the gelatin hollow capsule. Within the mass fraction range of the β-cyclodextrin and DL-sodium malate provided by the disclosure, a gelatin hollow capsule with balanced anti-fracture brittleness and moisturizing property is obtained, which widens the application scenarios of the gelatin hollow capsule and improves the stability during storage and transportation.

[0026] 3. The preparation method of the gelatin hollow capsule provided by the disclosure simplifies the preparation process of the capsule and reduces the cost of preparing the hollow capsule. BRIEF DESCRIPTION OF DRAWINGS

[0027] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed to be used in the embodiments or prior art description will be briefly introduced. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative labor.

[0028] Figure 1 The flow chart of the preparation method of the gelatin hollow capsule of the present application. DETAILED DESCRIPTION

[0029] The technical solutions in the embodiments of the present application will be described in detail below. Obviously, the described embodiments are only some of the embodiments of the present application, not all. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.

[0030] In one embodiment of the present disclosure, a gelatin hollow capsule is provided, which comprises, by weight fraction, 2400-2600 parts of purified water, 900-1000 parts of acid gelatin, 80-120 parts of pectin, 5-10 parts of β-cyclodextrin, 1-5 parts of DL-sodium malate, 15-40 parts of glacial acetic acid, and 12-15 parts of titanium white.

[0031] In this embodiment, acid gelatin is used as the base material, and pectin is added as a compound base material. The addition of pectin can cooperate with acid gelatin to form a tough and elastic capsule shell, thereby enhancing the strength and toughness of the gelatin capsule shell, making the capsule more durable and less prone to breakage. In this embodiment, β-cyclodextrin can be used as a plasticizing aid. β-cyclodextrin is a crown-shaped molecule containing seven glucose-based pyran rings, which is lipophilic (hydrophobic) inside and hydrophilic outside, forming a hollow molecular microcapsule structure. On the one hand, it can prevent the drug in the hollow capsule from being affected by moisture and deteriorating. On the other hand, it can improve the toughness of the formed hollow capsule and reduce its brittleness, thereby improving the stability of the capsule during storage and transportation. DL-sodium malate can be used as a humectant. During the preparation of the hollow capsule, DL-sodium malate can absorb and maintain a certain amount of water, forming a moist protective film that helps prevent the capsule shell from drying out and losing water. This moisture absorption and retention can help maintain the appropriate humidity of the capsule during storage and use, thereby improving its stability and service life. On the one hand, the DL-sodium malate humectant can regulate the water balance, keeping the moisture inside and outside the capsule shell at a relatively stable level. When the external environment is relatively humid, DL-sodium malate can absorb excess moisture to prevent the capsule from becoming too wet. When the external environment is relatively dry, it can release the stored water to maintain the moisture of the capsule shell. This ability to regulate water balance helps maintain the physical properties and stability of the hollow capsule. On the other hand, the moisturizing effect of DL-sodium malate can also enhance the flexibility of the capsule shell. By maintaining the moisture of the capsule shell, DL-sodium malate can prevent the shell from becoming brittle due to drying, thereby improving its resistance to breakage and wear. This enhanced flexibility helps ensure the integrity of the capsule during storage, transportation, and use, preventing drug leakage or failure.

[0032] In this embodiment, the synergistic effect of β-cyclodextrin and DL-sodium malate can be used to adjust the brittleness resistance and moisture retention of the hollow capsule by adjusting the ratio of β-cyclodextrin to DL-sodium malate, thereby improving the stability of the hollow capsule.

[0033] In one example, the mass ratio of β-cyclodextrin to DL-sodium malate can be 5:5, 6:4, 7:3, 8:2, or 9:1, by weight fraction.

[0034] Further, the mass ratio of the β-cyclodextrin to the sodium DL-malate is 8:2 by weight. In this ratio, the brittleness of the empty gelatin capsule is improved more obviously.

[0035] In an example, the acid method gelatin is at least one of acid method bone glue and acid method skin glue.

[0036] The disclosure also provides a preparation method of the above-mentioned gelatin empty capsule, as shown in the accompanying drawings, comprising the following steps: Figure 1

[0037] S10, adding the acid method gelatin into purified water at 60-75°C, stirring at 600-900 r / min for 10-20 min to obtain a gelatin glue solution;

[0038] S20, adding the pectin and the sodium DL-malate into the gelatin glue solution, heating to 80-85°C, and stirring at 600-900 r / min for 25-35 min to obtain a first mixed glue solution;

[0039] S30, obtaining a β-cyclodextrin water solution, adding the β-cyclodextrin water solution into the first mixed glue solution in step S20, stirring at 600-900 r / min for 50-75 min in a 50-60°C water bath to obtain a second mixed glue solution;

[0040] S40, adjusting the pH value of the second mixed glue solution to be acidic to obtain a capsule precursor solution; and sequentially performing glue conditioning, capsule making, drying, and assembling on the capsule precursor solution to obtain the gelatin empty capsule.

[0041] In this embodiment, by controlling the sol process, the brittleness and moisture retention of the gelatin empty capsule are improved, the capsule making process is simplified, and the production cost is effectively controlled.

[0042] In one embodiment of the disclosure, in step S40, the pH value of the capsule precursor solution is adjusted to 5.2-5.7 by using glacial acetic acid. The acid method gelatin has higher stability under weakly acidic conditions.

[0043] In one embodiment of the disclosure, in step S30, the obtaining of the β-cyclodextrin water solution comprises: mixing the β-cyclodextrin with purified water.

[0044] The mass ratio of the β-cyclodextrin to the purified water is 1:(16-22).

[0045] The temperature of the purified water is 50-70°C.

[0046] In an example, in step S40, the glue conditioning is placing the capsule precursor solution at a temperature of 45-65°C and keeping it stationary for at least 5 h.​

[0047] In one example, in step S40, the drying is drying the shaped capsule obtained by the making-up at 58% to 60% relative humidity and 20 to 30°C for 70 to 90 min.

[0048] The present disclosure also provides the use of the above-mentioned gelatin hollow capsule in the preparation of a capsule. Correspondingly, the capsule has the above-mentioned high anti-fragility and high moisturizing effect, and the details are not repeated here.

[0049] The gelatin hollow capsule provided by the present disclosure is further described below in combination with specific examples.

[0050] Example 1

[0051] The formula components are, by mass, acid bone glue: acid skin glue: pectin: purified water: β-cyclodextrin: DL-sodium malate = 700: 200: 100: 2500: 6: 4.

[0052] The preparation method of the gelatin hollow capsule of the present example includes the following steps:

[0053] S10, adding acid bone glue and acid skin glue into 70°C purified water, stirring at 750 r / min for 15 min to obtain a gelatin glue solution.

[0054] S20, adding pectin and DL-sodium malate into the gelatin glue solution, heating to 80°C, and stirring at 750 r / min for 30 min to obtain a first mixed glue solution.

[0055] S30, obtaining a β-cyclodextrin aqueous solution, adding the β-cyclodextrin aqueous solution into the first mixed glue solution in step S20, stirring at 750 r / min for 60 min in a 55°C water bath to obtain a second mixed glue solution. The mass ratio of β-cyclodextrin to purified water is 1:20; the temperature of the purified water is 60°C.

[0056] S40, adjusting the pH value of the second mixed glue solution to 5.5 to obtain a capsule precursor solution; the capsule precursor solution is sequentially subjected to color adjustment, glue conditioning, making-up, drying, and assembly to obtain a gelatin hollow capsule. The color adjustment is adding 1.5% titanium dioxide by mass fraction. The glue conditioning is placing the capsule precursor solution at a temperature of 55°C and keeping it still for 6 h. The drying is drying the shaped capsule obtained by the making-up at 58% to 60% relative humidity and 20 to 30°C (ambient temperature) for 80 min. The gelatin hollow capsule obtained in Example 1 is defined as gelatin hollow capsule 1.

[0057] Example 2

[0058] Example 2 differs from Example 1 in that the formulation components are, by mass, acid bone glue: acid skin glue: pectin: purified water: β-cyclodextrin: DL-sodium malate = 800: 200: 80: 2600: 10: 5.

[0059] The remaining steps are the same as in Example 1, and the gelatin hollow capsules prepared in this example are defined as gelatin hollow capsules 2.

[0060] Example 3

[0061] Example 3 differs from Example 1 in that the formulation components are, by mass, acid bone glue: acid skin glue: pectin: purified water: β-cyclodextrin: DL-sodium malate = 750: 200: 120: 2400: 8: 2.

[0062] The remaining steps are the same as in Example 1, and the gelatin hollow capsules prepared in this example are defined as gelatin hollow capsules 3.

[0063] Example 4

[0064] Example 4 differs from Example 1 in that the formulation components are, by mass, acid bone glue: acid skin glue: pectin: purified water: β-cyclodextrin: DL-sodium malate = 700: 200: 100: 2500: 6: 4.

[0065] In step S40, the pH value of the second mixed glue liquid is adjusted to 6.0, and a capsule precursor liquid is obtained.

[0066] The remaining steps are the same as in Example 1, and the gelatin hollow capsules prepared in this example are defined as gelatin hollow capsules 4.

[0067] Example 5

[0068] Example 5 differs from Example 1 in that the formulation components are, by mass, acid bone glue: acid skin glue: pectin: purified water: β-cyclodextrin: DL-sodium malate = 700: 200: 100: 2500: 7: 3.

[0069] In step S40, the pH value of the second mixed glue liquid is adjusted to 6.0, and a capsule precursor liquid is obtained.

[0070] The remaining steps are the same as in Example 1, and the gelatin hollow capsules prepared in this example are defined as gelatin hollow capsules 5.

[0071] Example 6

[0072] Example 6 differs from Example 1 in that the formulation components are, by mass, acid bone glue: acid skin glue: pectin: purified water: β-cyclodextrin: DL-sodium malate = 700: 200: 100: 2500: 8: 2.

[0073] In step S40, the pH value of the second mixed glue solution is adjusted to 6.0 to obtain a capsule precursor solution.

[0074] The remaining steps are the same as those of Example 1, and the obtained gelatin hollow capsule prepared in this example is defined as gelatin hollow capsule 6.

[0075] Example 7

[0076] Example 7 differs from Example 1 in that the formula components are, by mass, acid method bone glue: acid method skin glue: pectin: purified water: β-cyclodextrin: DL-sodium malate = 700: 200: 100: 2500: 6: 4.

[0077] In step S40, the pH value of the second mixed glue solution is adjusted to 6.5 to obtain a capsule precursor solution.

[0078] The remaining steps are the same as those of Example 1, and the obtained gelatin hollow capsule prepared in this example is defined as gelatin hollow capsule 7.

[0079] Example 8

[0080] Example 8 differs from Example 1 in that the formula components are, by mass, acid method bone glue: acid method skin glue: pectin: purified water: β-cyclodextrin: DL-sodium malate = 700: 200: 100: 2500: 7: 3.

[0081] In step S40, the pH value of the second mixed glue solution is adjusted to 6.5 to obtain a capsule precursor solution.

[0082] The remaining steps are the same as those of Example 1, and the obtained gelatin hollow capsule prepared in this example is defined as gelatin hollow capsule 8.

[0083] Example 9

[0084] Example 9 differs from Example 1 in that the formula components are, by mass, acid method bone glue: acid method skin glue: pectin: purified water: β-cyclodextrin: DL-sodium malate = 700: 200: 100: 2500: 8: 2.

[0085] In step S40, the pH value of the second mixed glue solution is adjusted to 6.5 to obtain a capsule precursor solution.

[0086] The remaining steps are the same as those of Example 1, and the obtained gelatin hollow capsule prepared in this example is defined as gelatin hollow capsule 9.

[0087] Comparative Example 1

[0088] Comparative Example 1 differs from Example 1 in that β-cyclodextrin is absent, as follows:

[0089] Formulation components: by mass, acid bone glue: acid skin glue: pectin: purified water: DL-sodium malate = 700: 200: 100: 2500: 4.

[0090] The preparation method of the gelatin empty capsule of Comparative Example 1 comprises the following steps:

[0091] S10, the acid bone glue and the acid skin glue are added into the purified water at 70℃, stirred at 750r / min for 15min, and a gelatin glue solution is obtained.

[0092] S20, the pectin and the DL-sodium malate are added into the gelatin glue solution, heated to 80℃, and stirred at 750r / min for 30min, and a capsule precursor solution is obtained.

[0093] S30, the pH value of the capsule precursor solution is adjusted to 5.5, and the capsule precursor solution is sequentially subjected to color adjustment, glue conditioning, blank making, drying, and assembly, and a gelatin empty capsule is obtained. The color adjustment is the addition of titanium dioxide with a mass fraction of 1.5%. The glue conditioning is that the capsule precursor solution is placed at a temperature of 55℃, and is kept at the temperature for 6h. The drying is that the formed capsule obtained by blank making is dried at a relative humidity of 58-60% and a temperature of 20-30℃ (ambient temperature) for 80min. The gelatin empty capsule obtained by Comparative Example 1 is defined as gelatin empty capsule 10.

[0094] Comparative Example 2

[0095] Comparative Example 2 is compared with Example 1, and the DL-sodium malate is absent, and the details are as follows:

[0096] Formulation components: by mass, acid bone glue: acid skin glue: pectin: purified water: β-cyclodextrin = 700: 200: 100: 2500: 6.

[0097] The preparation method of the gelatin empty capsule of Comparative Example 2 comprises the following steps:

[0098] S10, the acid bone glue and the acid skin glue are added into the purified water at 70℃, stirred at 750r / min for 15min, and a gelatin glue solution is obtained.

[0099] S20, the pectin is added into the gelatin glue solution, heated to 80℃, and stirred at 750r / min for 30min, and a first mixed glue solution is obtained.

[0100] S30, a β-cyclodextrin aqueous solution is obtained, the β-cyclodextrin aqueous solution is added into the first mixed glue solution in step S20, stirred at 750r / min for 60min in a 55℃ water bath, and a second mixed glue solution is obtained. The mass ratio of β-cyclodextrin to purified water is 1:20; and the temperature of the purified water is 60℃.

[0101] S40, adjusting the pH value of the second mixed glue solution to 5.5 to obtain a capsule precursor solution; the capsule precursor solution is sequentially subjected to color adjustment, glue conditioning, blank making, drying, and assembly to obtain a gelatin hollow capsule. The color adjustment is the addition of 1.5% by mass of titanium dioxide. The glue conditioning is the placement of the capsule precursor solution at a temperature of 55°C for 6 hours of heat preservation and standing. The drying is the drying of the formed capsule obtained by blank making at a relative humidity of 58%-60% and a temperature of 20-30°C (ambient temperature) for 80 minutes. The gelatin hollow capsule obtained by Comparative Example 2 is defined as gelatin hollow capsule 11.

[0102] Comparative Example 3

[0103] Comparative Example 3 is compared with Example 1 in that it lacks DL-sodium malate and β-cyclodextrin, and is as follows:

[0104] The formula components are, by mass, acid-process bone glue: acid-process skin glue: pectin: purified water = 700: 200: 100: 2500.

[0105] The method for preparing the gelatin hollow capsule of Comparative Example 3 includes the following steps:

[0106] S10, adding acid-process bone glue and acid-process skin glue to purified water at 70°C and stirring at 750 r / min for 15 minutes to obtain a gelatin glue solution.

[0107] S20, adding pectin to the gelatin glue solution, heating to 80°C, and stirring at 750 r / min for 30 minutes to obtain a first mixed glue solution.

[0108] S30, adjusting the pH value of the first mixed glue solution to 5.5 to obtain a capsule precursor solution; the capsule precursor solution is sequentially subjected to color adjustment, glue conditioning, blank making, drying, and assembly to obtain a gelatin hollow capsule. The color adjustment is the addition of 1.5% by mass of titanium dioxide. The glue conditioning is the placement of the capsule precursor solution at a temperature of 55°C for 6 hours of heat preservation and standing. The drying is the drying of the formed capsule obtained by blank making at a relative humidity of 58%-60% and a temperature of 20-30°C (ambient temperature) for 80 minutes. The gelatin hollow capsule obtained by Comparative Example 3 is defined as gelatin hollow capsule 12.

[0109] Comparative Example 4

[0110] Comparative Example 4 is compared with Example 1 in that it lacks DL-sodium malate, β-cyclodextrin, and pectin, and is as follows:

[0111] The formula components are, by mass, acid-process bone glue: acid-process skin glue: purified water = 700: 200: 2500.

[0112] The method for preparing the gelatin hollow capsule of Comparative Example 4 includes the following steps:

[0113] S10, add acid bone glue and acid skin glue into purified water at 70°C, stir at 750 r / min for 15 min, and obtain gelatin glue solution.

[0114] S20, adjust the pH value of the gelatin glue solution to 5.5, and obtain capsule precursor solution; the capsule precursor solution is sequentially subjected to color adjustment, gelatinizing, blank making, drying, and assembling, and gelatin hollow capsules are obtained. The color adjustment is adding titanium dioxide with a mass fraction of 1.5%. The gelatinizing is placing the capsule precursor solution at a temperature of 55°C, and standing for 6 h. The drying is drying the formed capsules obtained by blank making at a relative humidity of 58%-60% and a temperature of 20-30°C (ambient temperature) for 80 min. The gelatin hollow capsules obtained in Comparative Example 4 are defined as gelatin hollow capsules 13.

[0115] The gelatin hollow capsules 1-13 are subjected to friability test (see Table 1) and stability test (see Table 2).

[0116] Table 1. Results of friability test of gelatin hollow capsules 1-13

[0117]

[0118] (1) Friability test

[0119] Step 1, take 1 kg of blue silica gel, take it out after drying in a 105°C drying oven for 3 h, and immediately place it in a glass desiccator; place the desiccator in a constant temperature and humidity room at 20°C and 60% for 45 min, and record the actual temperature and humidity in the desiccator after balancing (20.5°C, 10%).

[0120] Step 2, take 400 capsules of each sample prepared in different examples or comparative examples each time, place them in a surface dish, evenly distribute 8 surface dishes containing the samples (50 capsules of each sample in each surface dish) in the silica gel desiccator, and then seal the desiccator for 24 h of moisture constant weight treatment.

[0121] Step 3, after completing the moisture constant weight, perform the friability test in a constant temperature and humidity room at 20°C and 60% ambient temperature and humidity. Take out one surface dish (50 capsules) at a time, and place them one by one into a glass tube (24 mm in inner diameter and 200 mm in length) standing on a wooden board (2 cm in thickness), drop a cylindrical weight (made of polytetrafluoroethylene, 22 mm in diameter, and 25 g±0.1 g in weight) from the mouth of the glass tube, observe whether the hollow capsules are broken, and record the number of broken capsules. The results are shown in Table 1.

[0122] As shown in Table 1, the friability results of gelatin hollow capsules 13 (comparative example 4) and gelatin hollow capsules 10-12 (comparative examples 1-3) are compared, and the addition of pectin can improve the flexibility of gelatin molecules to a certain extent, thereby improving the friability; after mixing pectin with acid gelatin, the friability of the capsule can be significantly improved.

[0123] As shown in Table 1, the friability results of gelatin hollow capsules 13 (comparative example 4) and gelatin hollow capsules 10-12 (comparative examples 1-3) are compared, and the addition of pectin can improve the flexibility of gelatin molecules to a certain extent, thereby improving the friability; after mixing pectin with acid gelatin, the friability of the capsule can be significantly improved.

[0124] In Table 1, the disintegration time and ignition residue of the gelatin hollow capsules prepared in each example and comparative example meet the requirements of the “2020 Chinese Pharmacopoeia Standards”; the disintegration time is ≦10 min, and the ignition residue is ≦5.0%.

[0125] Table 2. Stability test results of gelatin hollow capsules 1-13

[0126]

[0127]

[0128] (2) Stability accelerated test

[0129] The capsules were filled and sealed with Jianmin Chinese medicine powder, and the accelerated test (25℃±2℃, 65%±5%) was carried out for 12 months, and the powder properties were observed, and the powder moisture and capsule shell moisture were detected, and the results are shown in Table 2.

[0130] As shown in Table 2, compared with the gelatin hollow capsules prepared in the comparative examples, the water retention of the capsule samples modified by blending β-cyclodextrin and DL-malic acid sodium is improved, and the hygroscopicity of the powder is obviously improved.

[0131] The above only describes the preferred embodiments of the present application and does not limit the present application, and any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. A gelatin hollow capsule, characterized by, The purified water is 2400-2600 parts by weight, the acid gelatin is 900-1000 parts by weight, the pectin is 80-120 parts by weight, the beta-cyclodextrin is 5-10 parts by weight, the DL-sodium malate is 1-5 parts by weight, the glacial acetic acid is 15-40 parts by weight, and the titanium dioxide is 12-15 parts by weight.

2. The gelatin hollow capsule according to claim 1, characterized in that, The mass ratio of the beta-cyclodextrin to the DL-sodium malate is 8:

2.

3. A gelatin hollow capsule according to claim 1 or 2, c h a r a c t e r i z e d in that The acid gelatin is at least one of acid bone glue and acid skin glue.

4. A process for the production of the gelatin hollow capsule according to claim 1, characterized in that, The method comprises the following steps: S10, adding the acid gelatin into the purified water at 60-75°C, and stirring at 600-900 r / min for 10-20 min to obtain a gelatin glue solution; S20, adding the pectin and the DL-sodium malate into the gelatin glue solution, heating to 80-85°C, and stirring at 600-900 r / min for 25-35 min to obtain a first mixed glue solution; S30, obtaining a beta-cyclodextrin aqueous solution, adding the beta-cyclodextrin aqueous solution into the first mixed glue solution in step S20, and stirring at 600-900 r / min for 50-75 min in a 50-60°C water bath to obtain a second mixed glue solution; S40, adjusting the pH value of the second mixed glue solution to be acidic to obtain a capsule precursor solution; The capsule precursor solution is sequentially subjected to glue nourishing, blank making, drying, and assembling to obtain the gelatin hollow capsule.

5. The process for the preparation of gelatin hollow capsules according to claim 4, characterized in that, In step S40, the glacial acetic acid is used to adjust the pH value of the capsule precursor solution to 5.2-5.

7.

6. The process for the preparation of gelatin empty capsules according to claim 4, characterized in that, In step S30, the beta-cyclodextrin is mixed with the purified water to obtain the beta-cyclodextrin aqueous solution. The mass ratio of the beta-cyclodextrin to the purified water is 1:(16-22). The temperature of the purified water is 50-70°C.

7. Process for the production of gelatin hollow capsules according to any one of claims 4 to 6, characterized in that In step S40, the glue nourishing is to place the capsule precursor solution at a temperature of 45-65°C and keep it still for at least 5 h.

8. Process for the production of gelatin hollow capsules according to any one of claims 4 to 6, characterized in that In step S40, the drying is to dry the formed capsule obtained by blank making at a relative humidity of 58%-60% and a temperature of 20-30°C for 70-90 min.

9. Process for the production of gelatin hollow capsules according to any one of claims 4 to 6, characterized in that In step S40, before the glue nourishing, the capsule precursor solution further comprises adding the titanium dioxide for color adjustment.

10. The use of the gelatin hollow capsule in claim 1 in the preparation of a capsule.

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