One-step formed enteric gelatin empty capsule and preparation method thereof

Abstract

The invention belongs to the technical field of enteric capsule preparations, and particularly relates to a one-step formed enteric gelatin hollow capsule and a preparation method thereof.The enteric gelatin hollow capsule is prepared from, by weight, 80-150 parts of gelatin, 5-20 parts of plasticizer, 0.1-2 parts of opacifying agent, 0.01-2 parts of pigment and 150-300 parts of enteric material solution, the enteric-coated material is selected from a composition of at least two of cellulose acetate titanate, cellulose acetate ester, hydroxypropyl methylcellulose acetate succinate, low-methoxy pectin, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, lac, acrylic resin, and a copolymer of methyl methacrylate and methyl acrylate. According to the invention, through innovation in enteric-coated materials and preparation methods, organic solvents are not needed in preparation, the problems of waste liquid pollution and drug safety in the production and preparation process can be greatly reduced, and the prepared hollow capsule is safe and pollution-free and can be used for treatment of intestinal drugs.

Description

Technical Field

[0001] The invention belongs to the technical field of enteric-coated capsule preparations, and particularly relates to a one-step formed enteric-coated gelatin hollow capsule and a preparation method thereof. Background Art

[0002] Enteric-coated capsules refer to hollow hard capsules made of film-forming materials, excipients and suitable enteric-coated materials. They are insoluble in gastric juice but can disintegrate in intestinal juice to release active ingredients. They are suitable for filling drugs that are highly irritating to the stomach, degrade under acidic conditions or need to be released in the intestine. Enteric-coated capsules are currently widely used in clinical practice.

[0003] The market mainly focuses on double-coated enteric hollow capsules, that is, a layer of enteric coating material is coated on the surface of gastric-soluble hollow capsules. Under this process, enteric materials need to be dissolved using a large amount of organic solvents, such as acetone, ethanol or a mixture of the two. During the production process, most of the organic solvents evaporate into the environment, a small part is discharged into sewage through cleaning, and very little remains in the enteric capsule products. The use of a large amount of organic solvents will bring great safety hazards to fire safety and personnel health during the storage and manufacturing process. The capsules prepared at the same time not only have the problem of organic solvent residues, but also have problems such as uneven and rough capsule surfaces, which affect the filling and use of capsules. Summary of the invention

[0004] In view of the problem of residual organic solvent in current enteric-coated capsules mentioned in the background technology, the present invention provides a one-step formed enteric-coated gelatin hollow capsule and a preparation method thereof. The specific technical scheme is as follows:

[0005] First, the present invention provides an enteric gelatin hollow capsule formed at one time, which comprises the following components by weight: 80-150 parts of gelatin, 5-20 parts of plasticizer, 0.1-2 parts of sunscreen, 0.01-2 parts of pigment, and 150-300 parts of enteric material solution, wherein the enteric material is selected from at least two combinations of cellulose acetate titanate, cellulose acetate ester, hydroxypropyl methylcellulose acetate succinate, low-methoxy pectin, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, shellac, acrylic resin, methyl methacrylate and a copolymer of methyl acrylate.

[0006] Furthermore, the gelatin is prepared from pig or cattle skin and bone by acid method, alkali method or enzyme method, and the gelatin has a freezing strength greater than 250 bloom g and a viscosity greater than 4.5 mPa·s.

[0007] Furthermore, the enteric material is cellulose acetate titanate, hydroxypropyl methylcellulose acetate succinate and cellulose acetate phthalate in a weight ratio of 1-2:1-2:1-2 or cellulose acetate titanate and cellulose acetate phthalate in a weight ratio of 1:1.

[0008] Furthermore, the mass fraction of the enteric material in the enteric material solution is 10-30%, and the pH is 4-6.

[0009] Furthermore, the compound is at least one selected from glycerol, polyethylene glycol, triethyl citrate, polysorbate 80, castor oil, poloxamer, sorbitol, maltitol, mannitol, erythritol, propylene glycol, inositol, maltitol, triacetin, sorbic acid, triethyl glycerol, and polyvinyl alcohol.

[0010] Furthermore, the sunscreen is any one of titanium dioxide, zinc oxide and talcum powder, and the pigment is a synthetic pigment or a natural pigment.

[0011] The present invention also provides a method for preparing a one-step formed enteric-coated gelatin hollow capsule, comprising the following steps:

[0012] Step 1, adding plasticizer to purified water, heating the purified water until the plasticizer is dissolved, then adding gelatin and enteric material or enteric material solution thereto, stirring and vacuumizing to dissolve, and obtaining a mixed gelatin solution, keeping it warm for later use;

[0013] Step 2: pour the mixed glue into the mold, glue the mold, put it into a drying oven to dry it to obtain a blank, demould the blank, cut it, and put it together to obtain an enteric-coated gelatin hollow capsule.

[0014] Furthermore, the step 1 of preparing the enteric material comprises the following preparation steps: adding water to the enteric material, adding a pH adjuster thereto to adjust the pH to 4-6, and stirring to dissolve.

[0015] Furthermore, in the step 1, the heating temperature of the purified water is 50-90° C., the stirring time is 30-60 min, the vacuum degree of the vacuum pumping is 0.01 MPa, the vacuum pumping time is 15-30 min, and the insulation temperature is 40-60° C.

[0016] Furthermore, in step 2, the temperature of the drying oven is 20-50° C., the relative humidity is 50-70%, and the drying time is 1-2 hours.

[0017] Compared with the prior art, the present invention has the following beneficial effects:

[0018] The present invention is innovative in enteric materials and preparation methods. Compared with the prior art which mostly uses organic solvents as dissolving agents, the enteric materials used in the present invention can be dissolved without the participation of organic solvents, which can greatly reduce waste liquid pollution and drug safety issues in the production and preparation process. The prepared hollow capsules are safe and pollution-free and can be used for the treatment of intestinal drugs. At the same time, the enteric hollow capsules prepared by the present invention meet the pharmacopoeia standards in terms of technical indicators such as disintegration time, friability and drying loss, especially in the disintegration time, no cracks and disintegration will occur in simulated gastric juice, and only 30 minutes are required to completely disintegrate in artificial intestinal juice, which is conducive to the delivery and release of drugs.

[0019] Attached photos

[0020] Figure 1 This is a physical picture of the one-step formed enteric-coated gelatin hollow capsule of the present invention. DETAILED DESCRIPTION

[0021] In order to make the purpose, technical solution and advantages of the present invention more clear, the technical solution of the present invention will be clearly and completely described below in conjunction with embodiments.

[0022] Example 1

[0023] This embodiment provides a method for preparing a one-step formed enteric-coated gelatin hollow capsule, comprising the following steps:

[0024] Step 1, adding plasticizer to purified water, heating the purified water until the plasticizer is dissolved, then adding gelatin and enteric material solution thereto, stirring and vacuumizing to dissolve to obtain a mixed glue solution, adding a sunscreen and a pigment to the mixed glue solution, and then keeping it warm for use;

[0025] Specifically, 300 parts of purified water are taken, 5 parts of glycerol and 5 parts of polysorbate 80 are added thereto, and the mixture is heated to 70°C to dissolve. Then 100 parts of 280 bloom g gelatin and 300 parts of enteric material solution are added thereto in sequence. The enteric material solution includes cellulose acetate phthalate and cellulose acetate phthalate in a mass ratio of 1:1, water is added thereto, the pH is adjusted to 5 with a pH adjuster, and the cellulose acetate phthalate and cellulose acetate phthalate are dissolved by stirring to prepare an enteric material solution, and the mass fraction of cellulose acetate phthalate and cellulose acetate phthalate in the solution is 20%. Stir for 30 minutes, and vacuumize for 30 minutes under a vacuum degree of 0.01 MPa to obtain a mixed glue solution. 0.5 parts of pigment and 0.5 parts of talcum powder are added to the mixed glue solution, and the mixture is naturally cooled to 50°C and kept warm for standby use.

[0026] Step 2: pour the mixed glue into the mold, glue the mold, put it into a drying oven to dry it to obtain a blank, demould the blank, cut it, and put it together to obtain an enteric-coated gelatin hollow capsule.

[0027] Specifically, the mixed glue liquid is poured into the mold, and after the mold is glued, it is automatically pushed into a drying oven at 30°C and 60% relative humidity for drying for 1 hour to obtain a blank, and the blank is demoulded, cut, and fitted to obtain an enteric-coated gelatin hollow capsule.

[0028] The present embodiment also provides a one-time formed enteric-coated gelatin hollow capsule, which comprises the following components by weight: 100 parts of gelatin, 10 parts of plasticizer, 0.5 parts of sunscreen, 0.5 parts of pigment, and 300 parts of enteric-coated material solution.

[0029] Example 2

[0030] The difference between this embodiment and embodiment 1 is that the plasticizer is 10 parts of triethyl citrate and 5 parts of polysorbate 80. The number of parts of the enteric material solution is 200 parts, and the enteric material is a mixture of cellulose acetate titanate, hydroxypropyl methylcellulose acetate succinate and cellulose acetate phthalate in a weight ratio of 1:1:1.

[0031] Example 3

[0032] The difference between this embodiment and embodiment 1 is that the plasticizer is 5 parts of poloxamer, 2 parts of polysorbate 80 and 5 parts of castor oil. The number of parts of the enteric material solution is 300 parts, and the enteric material is low methoxyl pectin and shellac in a weight ratio of 1:2.

[0033] Comparative Example 1

[0034] The difference between this comparative example and Example 1 is that the plasticizer is 5 parts of poloxamer, 2 parts of polysorbate 80 and 5 parts of castor oil. The number of parts of the enteric material solution is 300 parts, and the enteric material is low-methoxy pectin.

[0035] Comparative Example 2

[0036] The difference between this comparative example and Example 1 is that the plasticizer is 10 parts of triethyl citrate and 5 parts of polysorbate 80. The number of parts of the enteric material is 200 parts, and the enteric material is cellulose acetate phthalate.

[0037] According to the test method of the Chinese Pharmacopoeia, various properties of the above embodiments and comparative examples were tested, and the data are shown in the following Table 1:

[0038] Table 1: Test results of examples and comparative examples

[0039]

[0040] From the above experimental results, it can be seen that the hollow capsules prepared by the embodiment of the technical solution of the present invention fully meet the pharmacopoeia standards and can be used as qualified drugs. At the same time, the enteric-coated hollow capsules prepared in the embodiment of the present invention do not need to use organic solvents in the preparation, which can greatly reduce the environmental pollution and drug safety generated in the preparation process.

[0041] Compared with the embodiment, only one enteric material was used in Comparative Examples 1 and 2, and the prepared hollow capsules had obvious defects in the disintegration time limit. Among them, the hollow capsules prepared by using only low-methoxyl pectin had cracks in simulated gastric juice, and it took 55 minutes to completely disintegrate in artificial intestinal juice, which did not meet the pharmacopoeia standard. The same was true for the hollow capsules prepared by using only cellulose acetate phthalate, which had cracks in simulated gastric juice, and it took nearly 70 minutes to completely disintegrate in artificial intestinal juice, which did not meet the pharmacopoeia standard.

[0042] In summary, the present invention is innovative in enteric materials and preparation methods. Compared with the prior art, which mostly uses organic solvents as dissolving agents, the enteric materials used in the present invention do not need to be dissolved in the presence of organic solvents, which can greatly reduce waste liquid pollution and drug safety issues in the production and preparation process. The prepared hollow capsules are safe and pollution-free and can be used for the treatment of intestinal drugs. At the same time, the enteric hollow capsules prepared by the present invention meet the pharmacopoeia standards in terms of technical indicators such as disintegration time, friability and loss on drying, especially in the disintegration time, no cracks and disintegration will occur in simulated gastric juice, and only 30 minutes are required to completely disintegrate in artificial intestinal juice, which is conducive to the delivery and release of drugs.

[0043] It is obvious to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the present invention can be implemented in other specific forms without departing from the spirit or essential features of the present invention. Therefore, the embodiments should be regarded as exemplary and non-restrictive from any point of view. In addition, it should be understood that although this specification is described in accordance with the embodiments, it does not contain only one technical solution. This narrative of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole, and the technical solutions in the embodiments can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A one-time formed enteric-coated gelatin hollow capsule, characterized in that: The invention comprises the following ingredients by weight: 80 to 150 parts of gelatin, 5 to 20 parts of plasticizer, 0.1 to 2 parts of sunscreen, 0.01 to 2 parts of pigment, and 150 to 300 parts of enteric material solution, wherein the enteric material is selected from at least two combinations of cellulose acetate titanate, cellulose acetate ester, hydroxypropyl methylcellulose acetate succinate, low-methoxy pectin, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, shellac, acrylic resin, methyl methacrylate and copolymer of methyl acrylate.

2. The one-step formed enteric-coated gelatin hollow capsule according to claim 1, characterized in that: The gelatin is prepared from pig or cattle skin and bone by acid method, alkali method or enzyme method, and the gelatin has a freezing strength greater than 250 bloom g and a viscosity greater than 4.5 mPa·s.

3. The one-step formed enteric-coated gelatin hollow capsule according to claim 1, characterized in that: The enteric material is cellulose acetate titanate, hydroxypropyl methylcellulose acetate succinate and cellulose acetate phthalate in a weight ratio of 1-2:1-2:1-2 or cellulose acetate titanate and cellulose acetate phthalate in a weight ratio of 1:

1.

4. The one-step formed enteric-coated gelatin hollow capsule according to claim 3, characterized in that: The mass fraction of the enteric material in the enteric material solution is 10-30%, and the pH is 4-6.

5. The one-step formed enteric-coated gelatin hollow capsule according to claim 1, characterized in that: The plasticizer is selected from at least one of glycerol, polyethylene glycol, triethyl citrate, polysorbate 80, castor oil, poloxamer, sorbitol, maltitol, mannitol, erythritol, propylene glycol, inositol, maltitol, triacetin, sorbic acid, triethyl glycerol, and polyvinyl alcohol.

6. The one-step formed enteric-coated gelatin hollow capsule according to claim 1, characterized in that: The sunscreen is any one of titanium dioxide, zinc oxide and talcum powder, and the pigment is a synthetic pigment or a natural pigment.

7. The method for preparing a one-step formed enteric-coated gelatin empty capsule according to any one of claims 1 to 6, characterized in that: The following steps are involved: Step 1, adding plasticizer to purified water, heating the purified water until the plasticizer is dissolved, then adding gelatin and enteric material solution thereto, stirring and vacuumizing to dissolve to obtain a mixed glue solution, adding a sunscreen and a pigment to the mixed glue solution, and then keeping it warm for use; Step 2: pour the mixed glue into the mold, glue the mold, put it into a drying oven to dry it to obtain a blank, demould the blank, cut it, and put it together to obtain an enteric-coated gelatin hollow capsule.

8. The method for preparing a one-step formed enteric-coated gelatin hollow capsule according to claim 7, characterized in that: The step 1 of preparing the enteric material comprises the following steps: adding water to the enteric material, adding a pH adjuster thereto to adjust the pH to 4-6, and stirring to dissolve.

9. The method for preparing a one-step formed enteric-coated gelatin hollow capsule according to claim 7, characterized in that: In the step 1, the heating temperature of the purified water is 50-90° C., the stirring time is 30-60 min, the vacuum degree of the vacuum pumping is 0.01 MPa, the vacuum pumping time is 15-30 min, and the insulation temperature is 40-60° C.

10. The method for preparing a one-step formed enteric-coated gelatin hollow capsule according to claim 7, characterized in that: In the step 2, the temperature of the drying oven is 20-50° C., the relative humidity is 50-70%, and the drying time is 1-2 hours.

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