Gelatin empty capsule as well as preparation method and application thereof

Abstract

The invention provides a gelatin hollow capsule as well as a preparation method and application thereof, and relates to the technical field of capsule preparations. The gelatin hollow capsule is prepared from the following components in parts by weight: 2400 to 2600 parts of purified water, 900 to 1000 parts of acid gelatin, 80 to 120 parts of pectin, 5 to 10 parts of beta-cyclodextrin, 1 to 5 parts of DL-sodium malate, 15 to 40 parts of glacial acetic acid and 12 to 15 parts of titanium dioxide. According to the hollow capsule provided by the invention, beta-cyclodextrin and DL-sodium malate are introduced for synergistic modification, so that the breakage and brittleness resistance and the moisturizing effect of the hollow capsule are improved.

Description

Technical Field

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

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

[0003] Under the conditions of the prior art, plasticizers and moisturizers are generally introduced to improve the brittleness of gelatin capsules. For example, the common plasticizer PEG slightly improves the brittleness of the capsule due to its good compatibility with gelatin. The screening and optimization of raw materials are also key factors affecting the brittleness of capsules. In the "Progress in Research on Polysaccharide-Protein Composite Hydrogels", it is outlined that a small amount of pectin (crystalline network structure, with good flexibility) molecules and gelatin molecules will improve the mechanical strength of the film material. The Chinese patent with publication number CN114732793A discloses a hollow capsule and a method for preparing the same. In this patent, zinc oxide is used as a sunscreen to improve the protective effect of the capsule on photosensitive drugs, but the capsule is not improved in terms of anti-brittleness and moisture retention. Therefore, in order to solve the brittleness problem of gelatin capsules, there is an urgent need for a method for preparing anti-brittle moisture-retaining gelatin hollow capsules with mature technology, simple preparation, and high safety.

[0004] It should be noted that the information disclosed in the above background technology section is only used to enhance the understanding of the background of the present disclosure, and therefore may include information that does not constitute the prior art known to ordinary technicians in the field. Summary of the invention

[0005] In view of this, the present invention provides a hollow gelatin capsule and a preparation method and application thereof, and improves the anti-fragility and moisturizing effect of the hollow gelatin capsule by adding an auxiliary agent.

[0006] The technical solution of the present invention is achieved in this way:

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

[0008] On the basis of the above technical solution, preferably, the mass ratio of the β-cyclodextrin to DL-sodium malate is 8:2 in parts by weight.

[0009] On the basis of the above technical solution, preferably, the acid-processed gelatin is at least one of acid-processed bone glue and acid-processed hide glue.

[0010] The present invention also provides a method for preparing the above-mentioned hollow gelatin capsule, comprising the following steps:

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

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

[0013] S30, obtaining a β-cyclodextrin aqueous solution, adding the β-cyclodextrin aqueous solution to 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;

[0014] 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 gelatin curing, blank making, drying, and assembly to obtain a gelatin hollow capsule.

[0015] On the basis of the above technical solution, 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] On the basis of the above technical solution, preferably, in step S30, obtaining the β-cyclodextrin aqueous solution comprises: mixing β-cyclodextrin with purified water;

[0017] Wherein, the mass ratio of the β-cyclodextrin to purified water is 1:(16-22);

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

[0019] On the basis of the above technical solution, it is preferably characterized in that, in step S40, the curing of the gel is to place the capsule precursor liquid at a temperature of 45 to 65° C. and keep it still for at least 5 hours.

[0020] On the basis of the above technical solution, preferably, in step S40, the drying is to dry the shaped capsules obtained by the blank making at a relative humidity of 58% to 60% and 20 to 30° C. for 70 to 90 minutes.

[0021] On the basis of the above technical solution, preferably, in step S40, the capsule precursor solution further includes adding titanium dioxide for color adjustment before curing the gelatin.

[0022] The present invention also provides an application of the above-mentioned empty gelatin capsule in preparing capsules.

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

[0024] 1. By adding pectin as a compound base material, pectin and acid-processed gelatin are combined to improve the toughness and elasticity of the empty gelatin capsules, and improve the anti-fragility of the empty gelatin capsules.

[0025] 2. The hollow gelatin capsules provided by the present disclosure add β-cyclodextrin as a plasticizer and DL-sodium malate as a moisturizing agent, and the two act synergistically to improve the anti-fragility of the hollow gelatin capsules while improving the moisturizing effect of the hollow gelatin capsules. Within the mass fraction range of β-cyclodextrin and DL-sodium malate provided by the present disclosure, hollow gelatin capsules with balanced anti-fragility and moisturizing properties are obtained, which broadens the application scenarios of hollow gelatin capsules and the stability during storage and transportation.

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

[0027] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

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

[0029] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

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

[0031] In this embodiment, acid gelatin is used as a base material, and pectin is added as a composite base material. By adding pectin, a tough and elastic capsule shell can be formed in combination with acid gelatin to enhance 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 plasticizer; β-cyclodextrin is a crown molecule containing 7 glucosylpyran 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 damp and deteriorating, and on the other hand, it can improve the toughness of the hollow capsule formed, reduce its brittleness, and improve the stability of the capsule during storage and transportation. DL-sodium malate can be used as a moisturizing aid; during the preparation of the hollow capsule, DL-sodium malate can absorb and maintain a certain amount of moisture, forming a moist protective film, which helps prevent the capsule shell from drying and losing water. This hygroscopicity and moisture retention can keep the capsule at an appropriate humidity during storage and use, thereby improving its stability and service life. On the one hand, the DL-sodium malate moisturizer can regulate the moisture balance and keep the moisture inside and outside the capsule shell at a relatively stable level. When the external environment humidity is high, DL-sodium malate can absorb excess moisture to prevent the capsule from being over-moistened; when the external environment humidity is low, it can release the stored moisture to maintain the moisture of the capsule shell. This ability to regulate moisture 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 cracking and wear. This enhanced flexibility helps ensure that the capsule maintains its integrity during storage, transportation and use, preventing drug leakage or failure.

[0032] Thus, in this embodiment, under the synergistic effect of β-cyclodextrin and DL-sodium malate, the anti-brittleness and moisture retention of the hollow capsule can be adjusted by adjusting the ratio of β-cyclodextrin and DL-sodium malate, thereby improving the stability of the hollow capsule.

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

[0034] Furthermore, in terms of weight, the mass ratio of the β-cyclodextrin to the DL-sodium malate is 8:2. Under this ratio, the β-cyclodextrin has a more obvious improvement on the brittleness of the empty capsule.

[0035] In one example, the acid-processed gelatin is at least one of acid-processed bone glue and acid-processed hide glue.

[0036] The present disclosure also provides a method for preparing the above-mentioned hollow gelatin capsule. Figure 1 As shown, the following steps are included:

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

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

[0039] S30, obtaining a β-cyclodextrin aqueous solution, adding the β-cyclodextrin aqueous solution to 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; the capsule precursor solution is sequentially subjected to gelatin curing, blank making, drying, and assembly to obtain a gelatin hollow capsule.

[0041] In this embodiment, by controlling the sol process, the anti-brittleness and moisture retention of the hollow gelatin capsules are improved, the complexity of the capsule making process is reduced, and the production cost can be effectively controlled.

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

[0043] In one embodiment of the present disclosure, in step S30, obtaining the β-cyclodextrin aqueous solution includes: mixing β-cyclodextrin with purified water;

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

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

[0046] In one example, in step S40, curing the gel is to place the capsule precursor solution at a temperature of 45 to 65° C. and keep it still for at least 5 hours.

[0047] In one example, in step S40, the drying is to dry the shaped capsules obtained by the blank making at a relative humidity of 58% to 60% and 20 to 30° C. for 70 to 90 minutes.

[0048] The disclosed embodiment also provides the use of the above-mentioned hollow gelatin capsule in preparing capsules. Accordingly, the capsules have the above-mentioned hollow capsules with high resistance to brittleness and excellent moisturizing effect, which will not be described in detail here.

[0049] The hollow gelatin capsules provided by the present disclosure are further described below in conjunction with specific embodiments.

[0050] Example 1

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

[0052] The preparation method of the hollow gelatin capsule of the present embodiment comprises the following steps:

[0053] S10. Add acid-processed bone glue and acid-processed hide glue into purified water at 70° C., stir at 750 r / min for 15 min, and obtain gelatin solution.

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

[0055] S30, obtaining a β-cyclodextrin aqueous solution, adding the β-cyclodextrin aqueous solution to 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, wherein the mass ratio of β-cyclodextrin to purified water is 1:20; and 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 coloring, glue curing, blanking, drying, and assembly to obtain a gelatin hollow capsule. Among them, the coloring is to add titanium dioxide with a mass fraction of 1.5%. Curing is to place the capsule precursor solution at a temperature of 55°C and keep it warm for 6 hours. Drying is to dry the shaped capsule obtained by blanking at a relative humidity of 58% to 60% and 20 to 30°C (ambient temperature) for 80 minutes. The gelatin hollow capsule obtained in Example 1 is defined as gelatin hollow capsule 1.

[0057] Example 2

[0058] The difference between Example 2 and Example 1 is that the formula components are calculated by mass as follows: acid-process bone glue: acid-process hide glue: pectin: purified water: β-cyclodextrin: DL-sodium malate = 800:200:80:2600:10:5.

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

[0060] Example 3

[0061] The difference between Example 3 and Example 1 is that the formula components are calculated by mass as follows: acid-process bone glue: acid-process hide glue: pectin: purified water: β-cyclodextrin: DL-sodium malate = 750:200:120:2400:8:2.

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

[0063] Example 4

[0064] The difference between Example 4 and Example 1 is that the formula components are calculated by mass as follows: acid-process bone glue: acid-process hide 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 gel solution is adjusted to 6.0 to obtain a capsule precursor solution.

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

[0067] Example 5

[0068] The difference between Example 5 and Example 1 is that the formula components are calculated by mass as follows: acid-process bone glue: acid-process hide 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 gel solution is adjusted to 6.0 to obtain a capsule precursor solution.

[0070] The remaining steps are the same as those in Example 1. The hollow gelatin capsule prepared in this example is defined as hollow gelatin capsule 5.

[0071] Example 6

[0072] The difference between Example 6 and Example 1 is that the formula components are calculated by mass as follows: acid-process bone glue: acid-process hide 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 gel solution is adjusted to 6.0 to obtain a capsule precursor solution.

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

[0075] Example 7

[0076] The difference between Example 7 and Example 1 is that the formula components are calculated by mass as follows: acid-process bone glue: acid-process hide 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 gel solution is adjusted to 6.5 to obtain a capsule precursor solution.

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

[0079] Example 8

[0080] The difference between Example 8 and Example 1 is that the formula components are calculated by mass as follows: acid-process bone glue: acid-process hide 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 gel solution is adjusted to 6.5 to obtain a capsule precursor solution.

[0082] The remaining steps are the same as those in Example 1. The hollow gelatin capsules prepared in this example are defined as hollow gelatin capsules 8.

[0083] Example 9

[0084] The difference between Example 9 and Example 1 is that the formula components are calculated by mass as follows: acid-process bone glue: acid-process hide 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 gel solution is adjusted to 6.5 to obtain a capsule precursor solution.

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

[0087] Comparative Example 1

[0088] Compared with Example 1, Comparative Example 1 lacks β-cyclodextrin, as follows:

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

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

[0091] S10. Add acid-processed bone glue and acid-processed hide glue into purified water at 70° C., stir at 750 r / min for 15 min, and obtain gelatin solution.

[0092] S20, adding pectin and sodium DL-malate to the gelatin solution, heating to 80°C, stirring at 750 r / min for 30 min, to obtain a capsule precursor solution.

[0093] S30, adjusting the pH value of the capsule precursor solution to 5.5, and the capsule precursor solution is sequentially subjected to coloring, curing, blanking, drying, and assembly to obtain a hollow gelatin capsule. Wherein, the coloring is to add 1.5% by mass of titanium dioxide. Curing is to place the capsule precursor solution at a temperature of 55°C and keep it warm for 6 hours. Drying is to dry the shaped capsule obtained by blanking at a relative humidity of 58-60% and 20-30°C (ambient temperature) for 80 minutes. The hollow gelatin capsule obtained in Comparative Example 1 is defined as hollow gelatin capsule 10.

[0094] Comparative Example 2

[0095] Compared with Example 1, Comparative Example 2 lacks DL-sodium malate, as follows:

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

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

[0098] S10. Add acid-processed bone glue and acid-processed hide glue into purified water at 70° C., stir at 750 r / min for 15 min, and obtain gelatin solution.

[0099] S20, adding pectin to the gelatin solution, heating to 80°C, stirring at 750 r / min for 30 min, to obtain a first mixed gelatin solution.

[0100] S30, obtaining a β-cyclodextrin aqueous solution, adding the β-cyclodextrin aqueous solution to 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, wherein the mass ratio of β-cyclodextrin to purified water is 1:20; and the temperature of the purified water is 60°C.

[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 coloring, glue curing, blanking, drying, and assembly to obtain a gelatin hollow capsule. Among them, the coloring is to add titanium dioxide with a mass fraction of 1.5%. Curing is to place the capsule precursor solution at a temperature of 55°C and keep it warm for 6 hours. Drying is to dry the shaped capsule obtained by blanking at a relative humidity of 58% to 60% and 20 to 30°C (ambient temperature) for 80 minutes. The gelatin hollow capsule obtained in Comparative Example 2 is defined as gelatin hollow capsule 11.

[0102] Comparative Example 3

[0103] Compared with Example 1, Comparative Example 3 lacks DL-sodium malate and β-cyclodextrin, as follows:

[0104] Formula components: by mass, acid-process bone glue: acid-process hide glue: pectin: purified water = 700:200:100:2500.

[0105] The preparation method of the hollow gelatin capsule of Comparative Example 3 comprises the following steps:

[0106] S10. Add acid-processed bone glue and acid-processed hide glue into purified water at 70° C., stir at 750 r / min for 15 min, and obtain gelatin solution.

[0107] S20, adding pectin to the gelatin solution, heating to 80°C, stirring at 750 r / min for 30 min, to obtain a first mixed gelatin 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 coloring, glue curing, blanking, drying, and assembly to obtain a gelatin hollow capsule. Among them, the coloring is to add titanium dioxide with a mass fraction of 1.5%. Curing is to place the capsule precursor solution at a temperature of 55°C and keep it warm for 6 hours. Drying is to dry the shaped capsule obtained by blanking at a relative humidity of 58% to 60% and 20 to 30°C (ambient temperature) for 80 minutes. The gelatin hollow capsule obtained in Comparative Example 3 is defined as gelatin hollow capsule 12.

[0109] Comparative Example 4

[0110] Compared with Example 1, Comparative Example 4 lacks DL-sodium malate, β-cyclodextrin and pectin, as follows:

[0111] Formula components: by mass, acid-based bone glue: acid-based hide glue: purified water = 700:200:2500.

[0112] The preparation method of the hollow gelatin capsule of Comparative Example 4 comprises the following steps:

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

[0114] S20, adjusting the pH value of the gelatin solution to 5.5 to obtain a capsule precursor solution; the capsule precursor solution is sequentially subjected to coloring, curing, blanking, drying, and assembly to obtain a gelatin hollow capsule. Among them, the coloring is to add titanium dioxide with a mass fraction of 1.5%. Curing is to place the capsule precursor solution at a temperature of 55°C and keep it warm for 6 hours. Drying is to dry the shaped capsule obtained by blanking at a relative humidity of 58% to 60% and 20 to 30°C (ambient temperature) for 80 minutes. The gelatin hollow capsule obtained in Comparative Example 4 is defined as gelatin hollow capsule 13.

[0115] The above-mentioned empty gelatin capsules 1-13 were tested for brittleness (see Table 1) and stability (see Table 2).

[0116] Table 1. Brittleness test results of empty gelatin capsules 1-13

[0117]

[0118] (1) Brittleness test

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

[0120] Step 2: Take 400 capsule samples prepared in different embodiments or comparative examples each time and place them in a watch glass. Evenly distribute 8 watch glasses containing samples (50 capsule samples in each watch glass) and place them in a silica gel desiccator. Then seal the desiccator and perform a 24-hour water constant weight treatment.

[0121] Step 3. After the water content is constant, the friability test is carried out in a constant temperature and humidity room at 20°C and 60% ambient temperature and humidity. Take out one watch glass (50 capsules) at a time, and put them one by one into a glass tube (with an inner diameter of 24 mm and a length of 200 mm) standing on a wooden board (thickness 2 cm). A cylindrical weight (made of polytetrafluoroethylene, with a diameter of 22 mm and a weight of 25 g ± 0.1 g) is freely dropped from the mouth of the glass tube to 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 the hollow gelatin capsule 13 (Comparative Example 4) and the hollow gelatin capsules 10-12 (Comparative Examples 1-3) are compared. The addition of pectin can improve the flexibility of the gelatin molecules to a certain extent, thereby improving the friability; after pectin is mixed with acid-processed gelatin, the friability of the capsule can be significantly improved.

[0123] As shown in Table 1, compared with gelatin hollow capsules 10-13, the blending of β-cyclodextrin and sodium DL-malate can significantly improve the brittleness of the capsules, and the greater the proportion of β-cyclodextrin in the modified additive, the more obvious the improvement effect. In addition, after the introduction of modified additives β-cyclodextrin and sodium DL-malate, the prepared gelatin hollow capsules have lower brittleness under weakly acidic conditions of pH 5.5.

[0124] In Table 1, the disintegration time and ignition residue requirements of the hollow gelatin capsules prepared in each embodiment and comparative example meet the "Pharmacopoeia of the People's Republic of China 2020 Standard"; disintegration time ≦10min, ignition residue ≦5.0%.

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

[0126]

[0127]

[0128] (2) Accelerated stability test

[0129] The capsules were filled and sealed with Jianmin Chinese medicine powder, and then packaged in ordinary packaging and subjected to accelerated testing (25°C ± 2°C, 65% ± 5%) for 12 months. The properties of the powder were observed, and the moisture content of the powder and the capsule shell was tested. The results are shown in Table 2.

[0130] As shown in Table 2, compared with the hollow gelatin capsules prepared in the comparative example, the water retention of the capsule samples modified by blending β-cyclodextrin and DL-sodium malate was improved, and the hygroscopicity problem of the drug powder was significantly improved.

[0131] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A hollow gelatin capsule, characterized in that: Calculated by weight, it includes 2400-2600 parts of purified water, 900-1000 parts of acid-process 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.

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

2.

3. The empty gelatin capsule according to claim 1 or 2, characterized in that: The acid-processed gelatin is at least one of acid-processed bone glue and acid-processed hide glue.

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

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

7.

6. The method for preparing the hollow gelatin capsule according to claim 4, characterized in that: In step S30, obtaining the β-cyclodextrin aqueous solution includes: mixing β-cyclodextrin with purified water; Wherein, the mass ratio of the β-cyclodextrin to purified water is 1:(16-22); The temperature of the purified water is 50-70°C.

7. The method for preparing a hollow gelatin capsule according to any one of claims 4 to 6, characterized in that: In step S40, the curing step is to place the capsule precursor solution at a temperature of 45 to 65° C. and keep it still for at least 5 hours.

8. The method for preparing a hollow gelatin capsule according to any one of claims 4 to 6, characterized in that: In step S40, the drying is to dry the shaped capsules obtained by the blank making at a relative humidity of 58% to 60% and 20 to 30°C for 70 to 90 minutes.

9. The method for preparing a hollow gelatin capsule according to any one of claims 4 to 6, characterized in that: In step S40, the capsule precursor solution further includes adding titanium dioxide for color adjustment before curing the glue.

10. Use of the empty gelatin capsule according to claim 1 in preparing capsules.

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