CN115068437B - Preparation method of benzbromarone capsules - Google Patents
Preparation method of benzbromarone capsules Download PDFInfo
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- CN115068437B CN115068437B CN202210927909.6A CN202210927909A CN115068437B CN 115068437 B CN115068437 B CN 115068437B CN 202210927909 A CN202210927909 A CN 202210927909A CN 115068437 B CN115068437 B CN 115068437B
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- benzbromarone
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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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1611—Inorganic compounds
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention discloses a preparation method of a benzbromarone capsule, which comprises the steps of premixing, primary dry-wet granulation, primary granule finishing, secondary dry granulation, secondary granule finishing, sieving, final mixing, capsule filling and the like. The invention adopts secondary dry granulation, so that the capsule is more compact, the drug release effect is consistent with that of a tablet, and the dissolution quantity can reach the same quality as that of a reference preparation. In addition, the invention adopts dry granulation, so that a plurality of steps of wet granulation are omitted, the process is simple, and the cost is saved.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a preparation method of a benzbromarone capsule.
Background
The benzbromarone is also called bromobenzoyl benzfuran, is a strong uric acid-removing benzofuran derivative, and has the effect of strong uric acid removal. The tribromoron not only can effectively inhibit reabsorption of renal tubules on uric acid, but also can promote excretion of uric acid, and has dual functions of reducing blood uric acid concentration.
The tribromoron is white or almost white crystal powder, is insoluble in water and slightly soluble in ethanol, and is generally prepared by a traditional method of crushing a tribromoron raw material and granulating and tabletting, and has the defects that the tribromoron raw material is crushed, the particle size is reduced, static electricity is easily generated, and therefore, a lump is easily formed due to the action of static electricity in subsequent granulation, the dissolution effect is poor, and the product quality is affected.
Disclosure of Invention
Aiming at the prior art, the invention provides a preparation method of a benzbromarone capsule, wherein the capsule is filled by a secondary dry granulation process, and the dissolution curve is consistent with that of a reference preparation.
In order to achieve the above purpose, the invention adopts the following technical scheme: a preparation method of benzbromarone capsules comprises the following steps:
1) Premixing
Sieving the tribromone and the corn starch together, and adding the sieved tribromone and the sieved corn starch into a hopper mixer for mixing;
2) Dry granulation
2.1 First dry granulation
Carrying out primary dry granulation on the premixed material by using a dry granulator;
2.2 First granule finishing
Granulating the materials after the first granulation by a crushing granulator and sieving;
2.3 Secondary dry granulation
Granulating the granulated material according to a second dry method;
2.4 Secondary finishing
Carrying out first grain sizing on the materials subjected to the second grain sizing through a crushing grain sizing machine, sieving the materials with a screen, and carrying out second grain sizing;
calculating the yield of the particles, and converting the consumption of the additional auxiliary materials according to the yield;
3) Sieving
Sieving lactose and low substituted hydroxypropyl cellulose respectively, and sieving pulvis Talci and magnesium stearate respectively;
4) Final mixing
Mixing before lubrication: adding the granules subjected to 2.4) granulation, the lactose subjected to conversion and the low-substituted hydroxypropyl cellulose into a mixer, and mixing;
lubrication: adding the converted talcum powder and magnesium stearate into a mixer, and mixing;
5) Capsule filling
Filling is performed using a capsule mould.
Wherein, in the step 1), the benzbromarone and the corn starch are screened by a 20-mesh screen; mixing time after sieving was 30min at 10rpm.
Wherein, the first granule finishing in the step 2.2) is carried out, and the screen is selected to be 250Q.
In the step 2.4), after the material is subjected to first grain sizing, the material is screened by a 250Q screen, and the material after passing through the 250Q screen is screened by an 040G screen, and then second grain sizing is performed.
In the step 3), lactose and low-substituted hydroxypropyl cellulose are respectively sieved by a 40-mesh sieve, and talcum powder and magnesium stearate are respectively sieved by a 60-mesh sieve.
Wherein, in the step 4), the mixing time of the mixing before lubrication is 45min, and the rotating speed is 10rpm;
the mixing time of the lubrication is 6min, and the rotating speed is 8rpm.
In the step 5), the capsule filling is performed by using a 3# capsule mold.
Wherein each of the benzbromarone capsules contains 50mg of benzbromarone, 10-50mg of corn starch, 20-90mg of lactose, 1-10mg of low-substituted hydroxypropyl cellulose, 0.5-5mg of talcum powder and 0.5-5mg of magnesium stearate.
Wherein each of the benzbromarone capsules contains 50mg of benzbromarone, 25mg of corn starch, 80mg of lactose, 5mg of low-substituted hydroxypropyl cellulose, 1mg of talcum powder and 1mg of magnesium stearate.
The existing tribromone on the market is mostly a tablet, and the tablet can release the slow-release drug through granulation or coating, but has the problems of poor dissolution and low bioavailability. The tribromone preparation rarely adopts capsules, because once the capsules are broken, contained medicinal powder leaks out to act immediately, and the capsules are broken in 2 and 3 minutes generally. The invention adopts secondary dry granulation, so that the capsule is more compact, the drug release effect is consistent with that of a tablet, and the dissolution quantity can reach the same quality as that of a reference preparation. In addition, the conventional capsules are wet-granulating, namely dry granules are prepared by a wet method and then are packaged into the capsules, water is added first and then the dry granules are dried in the wet-granulating process, the process is multiple, time and labor are wasted, and the cost is increased.
Detailed Description
The invention will be further illustrated with reference to specific examples. It is to be understood that these examples are illustrative of the present invention and are not intended to limit the scope of the present invention. Further, it is understood that various changes and modifications of the invention may be made by those skilled in the art after reading the disclosure of the invention, and such equivalents are intended to fall within the scope of the invention as defined by the claims.
Example 1:
table 1 shows the amounts of the raw materials of the components used for preparing the benzbromarone capsules.
TABLE 1
1. Premixing
Sieving tribromone and corn starch together with a 20-mesh screen, adding the sieved tribromone and corn starch into a hopper mixer, mixing for 30min at 10rpm;
2. dry granulation
2.1. First dry granulation
Carrying out primary dry granulation on the premixed material by using a dry granulator, wherein the granulation parameters are as follows:
| dry granulation parameters | Range |
| Feeder speed | 60～80rpm |
| Nip roll | 0.5～1.5mm |
| Rotation speed of press roller | 5～20rpm |
| Pressure of press roller | 60～100Bar |
2.2. First finishing
Granulating the granulated material by a crushing and granulating machine, and selecting a screen to be 250Q;
2.3. second dry granulation
Granulating the granulated material according to a second dry granulating method, wherein the granulating parameters are as follows:
| dry granulation parameters | Range |
| Feeder speed | 40～80rpm |
| Nip roll | 0.5～4.5mm |
| Rotation speed of press roller | 5～20rpm |
| Pressure of press roller | 60～100Bar |
2.4. Second finishing
Carrying out first granulation on the materials subjected to secondary granulation by a crushing granulator, sieving by a 250Q screen, and carrying out second granulation on the materials subjected to the 250Q pass through an 040G screen;
calculating the yield of the particles, and converting the consumption of the additional auxiliary materials according to the yield;
3. sieving
Sieving lactose and low substituted hydroxypropyl cellulose with 40 mesh sieve, respectively sieving pulvis Talci and magnesium stearate with 60 mesh sieve;
4. final mixing
Mixing before lubrication: adding the granulated particles, the lactose after conversion and the low-substituted hydroxypropyl cellulose into a mixer, and mixing for 45min at a rotating speed of 10rpm;
lubrication: adding the converted talcum powder and magnesium stearate into a mixer, and mixing for 6min at 8rpm;
5. capsule filling
Filling was performed using a 3# capsule mold.
| Theoretical loading per grain: | 162mg |
| theoretical net weight of 20 grains | 3.24g |
| Time limit of disintegration | Not more than 30min |
Example 2: dissolution Performance test
The comparison results of the dissolution curves of the benzbromarone capsule preparation, the reference preparation and the comparative preparation (wet granulation process capsule) prepared by the invention are shown in table 2. The tribromone capsule imitated preparation (specification: 50mg, lot: BEC211103, BEC211104, BEC 211105) and the reference preparation (trade name: URINORM, specification: 50mg, lot: NIC081, morphology: tablet) of the comparative preparation were compared in terms of average elution amount of 12 tablets in pH7.5 phosphate buffer (containing 0.25% sodium dodecyl sulfate) in wet granulation process capsules (specification: 50mg, lot: 200422, 200723, 200906). As can be seen from table 2, the dissolution profiles (5 minutes, 10 minutes, 15 minutes, 20 minutes and 30 minutes) of the capsule samples prepared by the secondary dry granulation of the present invention are similar to the tablets of the reference formulation. The in vitro dissolution behavior of each batch of the capsule preparation prepared by the invention is consistent with that of the tablets of the reference preparation, and the quality of the capsule preparation is the same as that of the original ground product.
The invention adopts secondary dry granulation, so that the capsule is more compact, the drug release effect is consistent with that of a tablet, and the dissolution quantity can reach the same quality as that of a reference preparation. In addition, the invention adopts dry granulation, so that a plurality of steps of wet granulation are omitted, the process is simple, and the cost is saved.
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (8)
1. The preparation method of the benzbromarone capsule is characterized by comprising the following steps of:
1) Premixing
Sieving the tribromone and the corn starch together, and adding the sieved tribromone and the sieved corn starch into a hopper mixer for mixing;
2) Dry granulation
2.1 First dry granulation
Carrying out primary dry granulation on the premixed material by using a dry granulator;
2.2 First granule finishing
Granulating the materials after the first granulation by a crushing granulator and sieving;
2.3 Secondary dry granulation
Granulating the granulated material according to a second dry method;
2.4 Secondary finishing
The materials after the second granulation are subjected to first granulation by a crushing granulator, and are sieved by a screen, and then subjected to second granulation;
calculating the yield of the particles, and converting the consumption of the additional auxiliary materials according to the yield;
3) Sieving
Sieving lactose and low substituted hydroxypropyl cellulose respectively, and sieving pulvis Talci and magnesium stearate respectively;
4) Final mixing
Mixing before lubrication: adding the granules subjected to 2.4) granulation, the lactose subjected to conversion and the low-substituted hydroxypropyl cellulose into a mixer, and mixing;
lubrication: adding the converted talcum powder and magnesium stearate into a mixer, and mixing;
5) Capsule filling
Filling with a capsule mould;
each of the benzbromarone capsules contains 50mg of benzbromarone, 10-50mg of corn starch, 20-90mg of lactose, 1-10mg of low-substituted hydroxypropyl cellulose, 0.5-5mg of talcum powder and 0.5-5mg of magnesium stearate.
2. The method for preparing the tribromone capsules according to claim 1, wherein in the step 1), the tribromone and the corn starch are screened together through a 20-mesh screen; mixing time after sieving was 30min at 10rpm.
3. The method for preparing the benzbromarone capsule according to claim 1, wherein the first granule finishing in the step 2.2) is performed with a screen mesh of 250Q.
4. The method for preparing the benzbromarone capsule according to claim 1, wherein in the step 2.4), after the material is granulated for the first time, the material is sieved by a 250Q sieve, and the material passing through the 250Q sieve is sieved by a 040G sieve, and then the second time of granulating is performed.
5. The method for preparing the benzbromarone capsule according to claim 1, wherein in the step 3), lactose and low-substituted hydroxypropyl cellulose are respectively sieved by a 40-mesh sieve, and talcum powder and magnesium stearate are respectively sieved by a 60-mesh sieve.
6. The method for preparing a benzbromarone capsule according to claim 1, characterized in that in said step 4), said mixing time of mixing before lubrication is 45min, and the rotation speed is 10rpm;
the mixing time of the lubrication is 6min, and the rotating speed is 8rpm.
7. The method for preparing a tribromone capsule according to claim 1, wherein in the step 5), the capsule filling is performed using a 3# capsule mold.
8. The preparation method of the benzbromarone capsule according to claim 1, wherein each benzbromarone capsule contains 50mg of benzbromarone, 25mg of corn starch, 80mg of lactose, 5mg of low-substituted hydroxypropyl cellulose, 1mg of talcum powder and 1mg of magnesium stearate.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202210927909.6A CN115068437B (en) | 2022-08-03 | 2022-08-03 | Preparation method of benzbromarone capsules |
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| CN202210927909.6A CN115068437B (en) | 2022-08-03 | 2022-08-03 | Preparation method of benzbromarone capsules |
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| CN115068437A CN115068437A (en) | 2022-09-20 |
| CN115068437B true CN115068437B (en) | 2023-06-06 |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102429881A (en) * | 2011-12-01 | 2012-05-02 | 常州康普药业有限公司 | Method for preparing benzbromarone tablets |
| CN113425718A (en) * | 2021-05-13 | 2021-09-24 | 浙江歌文达生物医药科技有限公司 | Compound preparation for treating hyperuricemia and gout |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3639822A1 (en) * | 2018-10-15 | 2020-04-22 | Universität Regensburg | Compound for use in the treatment of a disease characterized by dysregulated mucus production and/or secretion |
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- 2022-08-03 CN CN202210927909.6A patent/CN115068437B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102429881A (en) * | 2011-12-01 | 2012-05-02 | 常州康普药业有限公司 | Method for preparing benzbromarone tablets |
| CN113425718A (en) * | 2021-05-13 | 2021-09-24 | 浙江歌文达生物医药科技有限公司 | Compound preparation for treating hyperuricemia and gout |
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