CN106913556B - Rifapentine capsule and preparation method thereof - Google Patents
Rifapentine capsule and preparation method thereof Download PDFInfo
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- CN106913556B CN106913556B CN201710269004.3A CN201710269004A CN106913556B CN 106913556 B CN106913556 B CN 106913556B CN 201710269004 A CN201710269004 A CN 201710269004A CN 106913556 B CN106913556 B CN 106913556B
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- rifapentine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5015—Organic compounds, e.g. fats, sugars
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
- A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
Abstract
The invention discloses a rifapentine capsule and a preparation method thereof, wherein Tween 80, HPMC and K are added12Adding pure ethanol to dissolve into a binder, and spraying the rifapentine by using the binder to prepare rifapentine particles; dissolving HPMC, BHA and vitamin C in pure ethanol to obtain coating solution, and spray coating the rifapentine granules with the coating solution to obtain rifapentine coated granules; and finally, mixing the rifapentine coated particles with pregelatinized starch, and filling to obtain the rifapentine capsule. The rifapentine capsule prepared by the method solves the problem of the fluidity of the intermediate powder of the original rifapentine capsule, thereby solving the problems of overproof related substances and large difference of loading capacity, and simultaneously greatly improving the dissolution rate.
Description
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to a rifapentine capsule and a preparation method thereof.
Background
The traditional preparation process of the rifapentine capsule is that powder is directly mixed, and the process is that raw and auxiliary materials are sieved and then mixed for minutes by a multidirectional motion mixer. The characteristic factors (brick red or dark red crystalline powder, fine powder and certain specific viscosity) of the main drug in the product increase the production difficulty of the filling process, so the physical and chemical properties of the main drug influence the loading difference and the dissolution rate, the original process cannot effectively improve the fluidity of the powder, and the phenomena of overproof capsule loading difference and large pill weight difference are easily caused during the production of the filling process. Meanwhile, rifapentine is unstable to water, raw materials are not treated by the original process, and the raw materials are easily degraded in a storage period, so that related substances exceed standards.
Disclosure of Invention
The invention provides a rifapentine capsule and a preparation method thereof, aiming at solving the problem of large difference of the loading capacity of the rifapentine capsule generated by directly mixing and granulating original powder in the prior art.
In order to achieve the purpose, the invention adopts the following technical scheme:
the first aspect of the present invention provides a preparation method of rifapentine capsule, which is prepared from tween 80, HPMC and K12Adding pure ethanol to dissolve into a binder, and spraying the rifapentine raw material by using the binder to prepare rifapentine particles; dissolving HPMC, BHA and vitamin C in pure ethanol to obtain coating solution, and spray coating the rifapentine granules with the coating solution to obtain rifapentine coated granules; and finally, mixing the rifapentine coated particles with pregelatinized starch, and filling to obtain the rifapentine capsule.
Further, the preparation method of the rifapentine capsule specifically comprises the following steps:
1) mixing Tween 80, HPMC and K12Adding pure ethanol to dissolve into adhesive, and sieving with 100 mesh sieve;
2) putting the rifapentine in a prescription amount into a granulating and coating pot, starting top spraying granulation when the temperature of materials in the granulating and coating pot reaches 35 ℃, controlling the temperature of the materials to be below 40 ℃ in the whole granulating process until the materials are completely sprayed, and sieving the materials by a 20-mesh sieve to remove particles larger than 20 meshes to obtain the rifapentine particles;
3) dissolving HPMC, BHA and vitamin C in pure ethanol to obtain coating solution, and sieving with 100 mesh sieve;
4) bottom-spraying coating is carried out on the rifapentine granules prepared in the step 2) by adopting the coating solution prepared in the step 3), the temperature of materials is controlled below 40 ℃ in the whole coating process until the materials are completely sprayed, the materials pass through a 20-mesh screen, and granules larger than 20 meshes are removed to prepare the rifapentine coated granules;
5) finally, the rifapentine coated particles coated in the step 4) are mixed with pregelatinized starch for total mixing and then are refilled to obtain the product.
Further preferably, in the preparation method of the rifapentine capsule, the rifapentine granules are prepared from the following components in parts by weight:
further preferably, in the preparation method of the rifapentine capsule, the rifapentine granules are prepared from the following components in parts by weight:
more preferably, in the preparation method of the rifapentine capsule, the rifapentine granules are prepared from the following components in parts by weight:
further preferably, in the preparation method of the rifapentine capsule, the rifapentine coated particles are prepared from the following components in parts by weight:
more preferably, in the preparation method of the rifapentine capsule, the rifapentine coated particles are prepared from the following components in parts by weight:
more preferably, in the preparation method of the rifapentine capsule, the rifapentine coated particles are prepared from the following components in parts by weight:
further preferably, in the preparation method of the rifapentine capsule, the temperature of the material in the step 2) is controlled to be 30-40 ℃.
More preferably, in the preparation method of the rifapentine capsule, the material temperature in the step 2) is controlled to be 32-35 ℃.
Further preferably, in the preparation method of the rifapentine capsule, the material temperature in the step 3) is controlled to be 25-35 ℃.
More preferably, in the preparation method of the rifapentine capsule, the material temperature in the step 3) is controlled to be 28-32 ℃.
In a second aspect of the present invention, there is provided a rifapentine capsule prepared by the above method.
By adopting the technical scheme, compared with the prior art, the invention has the following technical effects:
in the invention, Tween 80, HPMC and K are mixed12The rifapentine raw materials are sprayed into particles by adding pure ethanol to dissolve into a binder, then HPMC, BHA and vitamin C are added into pure ethanol to dissolve into a coating solution to spray liquid for coating the rifapentine particles, and finally the rifapentine particles are mixed with pregelatinized starch and then refilled, so that the problem of fluidity of the intermediate powder for preparing the rifapentine capsules in the prior art is solved, the problems of excessive substances and large difference of loading amount are solved, and the dissolution rate is greatly improved.
Detailed Description
The preparation method of the rifapentine capsule provided by the invention is to produce the rifapentine capsule by a fluidized bed granulation method, and the tween 80, the HPMC and the K are added12Adding pure ethanol to dissolve into a binder, and spraying the rifapentine raw material by using the binder to prepare rifapentine particles; dissolving HPMC, BHA and vitamin C in pure ethanol to obtain coating solution, and spray coating the rifapentine granules with the coating solution to obtain rifapentine coated granules; finally, the rifapentine coated particles are mixed with pregelatinized starch and then filled to obtain the rifapentine coated particlesRifapentine capsules. Solves the problem of large difference of the loading capacity of the rifapentine capsule generated by directly mixing and granulating the original powder, and simultaneously improves the dissolution rate and the quality of related substances.
The dosage and the source of each raw material and auxiliary material adopted by the embodiment of the invention are shown in the following table:
table one dosage and source of each raw and auxiliary material
The present invention will be described in detail and specifically with reference to the following examples to facilitate better understanding of the present invention, but the following examples do not limit the scope of the present invention.
Example 1 preparation of rifapentine capsules
(one) raw and auxiliary materials prescription (10000 granules per dose)
The rifapentine granules are prepared from the following components in parts by weight:
the rifapentine coated granule is prepared from the following components in parts by weight:
(II) concrete preparation process
1) Adding tween 80, HPMC and K12 into pure ethanol, dissolving into adhesive, and sieving with 100 mesh sieve;
2) putting the rifapentine in a prescription amount into a granulating and coating pot, starting top spraying granulation when the temperature of materials in the granulating and coating pot reaches 35 ℃, controlling the temperature of the materials to be 40 ℃ in the whole granulating process until the materials are completely sprayed, sieving the materials by a 20-mesh sieve, and removing particles larger than 20 meshes to obtain rifapentine particles;
3) dissolving HPMC, BHA and vitamin C in pure ethanol to obtain coating solution, and sieving with 100 mesh sieve;
4) bottom-spraying coating is carried out on the rifapentine granules prepared in the step 2) by adopting the coating solution prepared in the step 3), the temperature of materials is controlled at 40 ℃ in the whole coating process until the materials are completely sprayed, the materials pass through a 20-mesh screen, and granules larger than 20 meshes are removed to prepare the rifapentine coated granules;
5) finally, the rifapentine coated particles coated in the step 4) are mixed with pregelatinized starch for total mixing and then refilled to prepare the rifapentine capsule X160301.
Example 2 preparation of rifapentine capsules
(one) raw and auxiliary materials prescription (10000 granules per dose)
The rifapentine granules are prepared from the following components in parts by weight:
the rifapentine coated granule is prepared from the following components in parts by weight:
(II) concrete preparation process
1) Adding tween 80, HPMC and K12 into pure ethanol, dissolving into adhesive, and sieving with 100 mesh sieve;
2) putting the rifapentine in a prescription amount into a granulating and coating pot, starting top spraying granulation when the temperature of materials in the granulating and coating pot reaches 35 ℃, controlling the temperature of the materials to be 30-35 ℃ in the whole granulating process until the materials are completely sprayed, and sieving the materials by a 20-mesh sieve to remove particles larger than 20 meshes to obtain the rifapentine particles;
3) dissolving HPMC, BHA and vitamin C in pure ethanol to obtain coating solution, and sieving with 100 mesh sieve;
4) bottom-spraying coating is carried out on the rifapentine granules prepared in the step 2) by adopting the coating solution prepared in the step 3), the temperature of materials is controlled to be 30-35 ℃ in the whole coating process until the materials are completely sprayed, the materials pass through a 20-mesh screen, and granules larger than 20 meshes are removed to prepare the rifapentine coated granules;
5) finally, the rifapentine coated particles coated in the step 4) are mixed with pregelatinized starch for total mixing and then refilled to prepare the rifapentine capsule X160302.
EXAMPLE 3 preparation of Rifapentine capsules
(one) raw and auxiliary materials prescription (10000 granules per dose)
The rifapentine granules are prepared from the following components in parts by weight:
the rifapentine coated granule is prepared from the following components in parts by weight:
(II) concrete preparation process
1) Adding tween 80, HPMC and K12 into pure ethanol, dissolving into adhesive, and sieving with 100 mesh sieve;
2) putting the rifapentine in a prescription amount into a granulating and coating pot, starting top spraying granulation when the temperature of materials in the granulating and coating pot reaches 35 ℃, controlling the temperature of the materials to be 35-40 ℃ in the whole granulating process until the materials are completely sprayed, and sieving the materials by a 20-mesh sieve to remove particles larger than 20 meshes to obtain the rifapentine particles;
3) dissolving HPMC, BHA and vitamin C in pure ethanol to obtain coating solution, and sieving with 100 mesh sieve;
4) bottom-spraying coating is carried out on the rifapentine granules prepared in the step 2) by adopting the coating solution prepared in the step 3), the temperature of materials is controlled to be 25-30 ℃ in the whole coating process until the materials are completely sprayed, the materials pass through a 20-mesh screen, and granules larger than 20 meshes are removed to prepare the rifapentine coated granules;
5) finally, the rifapentine coated particles coated in the step 4) are mixed with pregelatinized starch for total mixing and then refilled to prepare the rifapentine capsule X160303.
Performance investigation: preparing rifapentine capsules by a traditional original process powder direct mixing method, and randomly selecting three batches of samples 150501, 150502 and 150503 as control samples; three batches of rifapentine capsules X160301, X160302 and X160303 prepared in examples 1-3 of the invention are taken as test samples, accelerated tests are respectively carried out, and the test results are shown in the following table two:
table two control sample and test sample accelerated test each test item test result
And (4) qualified standard: the loading difference is less than or equal to 10 percent, the content is 90-110 percent, the dissolution is more than or equal to 70 percent, the single impurity is less than or equal to 1.0 percent, and the total impurity is less than or equal to 3.0 percent.
As shown in the data of the table two, compared with the original process, the new process product has great improvement on the loading difference, and the problem of unstable loading in the prior art is completely solved; meanwhile, after the process is accelerated for 6 months, no matter single impurities or total impurities are in the allowable range of pharmacopoeia, and the stability is greatly improved compared with the prior art; in addition, the dissolution data show that the new process is also improved to a certain extent compared with the original process.
The embodiments of the present invention have been described in detail, but the embodiments are merely examples, and the present invention is not limited to the embodiments described above. Any equivalent modifications and substitutions to those skilled in the art are also within the scope of the present invention. Accordingly, equivalent changes and modifications made without departing from the spirit and scope of the present invention should be covered by the present invention.
Claims (6)
1. A method for preparing rifapentine capsule is characterized in that Tween 80, HPMC and K are added12Adding pure ethanol to dissolve into a binder, and spraying the rifapentine by using the binder to prepare rifapentine particles; dissolving HPMC, BHA and vitamin C in pure ethanol to obtain coating solution, and spray coating the rifapentine granules with the coating solution to obtain rifapentine coated granules; finally, mixing the rifapentine coated particles with pregelatinized starch, and filling to obtain a rifapentine capsule;
wherein, the rifapentine granules are prepared from the following components in parts by weight:
rifapentine 1500 parts
Polysorbate 8030 parts
Sodium dodecyl sulfate (K)12) 3 portions of
Hydroxypropyl cellulose (HPMC) 10 parts
667 parts of pure ethanol;
the rifapentine coated particle is prepared from the following components in parts by weight:
rifapentine particle 1200-1800 parts
1.2-1.8 parts of tert-butyl-4-hydroxyanisole (BHA)
8-12 parts of hydroxypropyl cellulose (HPMC)
1.2 to 1.8 portions of vitamin C
500 portions of pure ethanol.
2. The method of preparing a rifapentine capsule according to claim 1, comprising the following steps:
1) mixing Tween 80, HPMC and K12Adding pure ethanol to dissolve into adhesive, and sieving with 100 mesh sieve;
2) putting the rifapentine in a prescription amount into a granulating and coating pot, starting top spraying granulation when the temperature of materials in the granulating and coating pot reaches 35 ℃, controlling the temperature of the materials to be below 40 ℃ in the whole granulating process until the materials are completely sprayed, and sieving the materials by a 20-mesh sieve to remove particles larger than 20 meshes to obtain the rifapentine particles;
3) dissolving HPMC, BHA and vitamin C in pure ethanol to obtain coating solution, and sieving with 100 mesh sieve;
4) bottom-spraying coating is carried out on the rifapentine granules prepared in the step 2) by adopting the coating solution prepared in the step 3), the temperature of materials is controlled below 40 ℃ in the whole coating process until the materials are completely sprayed, the materials pass through a 20-mesh screen, and granules larger than 20 meshes are removed to prepare the rifapentine coated granules;
5) finally, the rifapentine coated particles coated in the step 4) are mixed with pregelatinized starch for total mixing and then are refilled to obtain the product.
3. The preparation method of the rifapentine capsule according to claim 1, characterized in that, the rifapentine coated granule is prepared from the following components in parts by weight:
rifapentine granules 1500 parts
1.5 parts of tert-butyl-4-hydroxyanisole (BHA)
Hydroxypropyl cellulose (HPMC) 10 parts
Vitamin C1.5 parts
667 portions of pure ethanol.
4. The method for preparing rifapentine capsules according to claim 2, wherein the temperature of the material in step 2) is controlled to 30-40 ℃.
5. The method for preparing rifapentine capsules according to claim 2, wherein the temperature of the material in step 3) is controlled to 25-35 ℃.
6. A rifapentine capsule prepared according to the process of any one of claims 1 to 5.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201710269004.3A CN106913556B (en) | 2017-04-24 | 2017-04-24 | Rifapentine capsule and preparation method thereof |
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| CN201710269004.3A CN106913556B (en) | 2017-04-24 | 2017-04-24 | Rifapentine capsule and preparation method thereof |
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| CN106913556B true CN106913556B (en) | 2021-03-02 |
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| CN102805740A (en) * | 2011-05-30 | 2012-12-05 | 浙江京新药业股份有限公司 | Rivastigmine capsules and preparation method thereof |
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