CN102836156A - Capsule containing flupirtine maleate and preparation method thereof - Google Patents
Capsule containing flupirtine maleate and preparation method thereof Download PDFInfo
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- CN102836156A CN102836156A CN2012103217340A CN201210321734A CN102836156A CN 102836156 A CN102836156 A CN 102836156A CN 2012103217340 A CN2012103217340 A CN 2012103217340A CN 201210321734 A CN201210321734 A CN 201210321734A CN 102836156 A CN102836156 A CN 102836156A
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- maleic acid
- magnesium stearate
- hydrogen phosphate
- granule
- mix homogeneously
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Abstract
The invention relates to a medicinal composition containing flupirtine maleate and a preparation method of the medicinal composition containing flupirtine maleate. The flupirtine maleate composition provided by the invention contains dried solid particles containing flupirtine maleate and a pharmaceutically acceptable adjuvant which is not contained in the particles. The composition is high in storage stability.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to a kind of capsule that contains the maleic acid Flupirtine and preparation method thereof.
Background of invention
Maleic acid Flupirtine (Katadolon; 2-amino-6-[(4-luorobenzyl) amino] pyridine-3-urethanes) be the nonopioid analgesic of central action.Structure is following:
Flupirtine is with the form of maleate, has been successfully used to treat neuralgia for example, pain, headache and the postoperative pain relevant with degenerative arthritis for many years.According to DE4122166AI, the maleic acid Flupirtine also can be used as the medicament of control disease or pathologic symptom, and said disease or symptom are based on the muscular tone or the result of muscular tone.
The maleic acid Flupirtine is met auroral poles and is prone to degraded, and is difficult for preserving.We are through research for a long time, and the at present commercially available maleic acid Flupirtine capsule shelf-life is short, poor stability, and dissolution is low, and active component content reduces after placing after a while, and impurity increases.
Summary of the invention
The object of the invention is to provide a kind of good stability, and dissolution is high, the pharmaceutical composition of reliable quality maleic acid Flupirtine.
The solid, dry granule that pharmaceutical composition of the present invention comprises the maleic acid Flupirtine reaches pharmaceutically acceptable adjuvant.
Pharmaceutical composition according to the invention, be processed into by following composition:
According to one of embodiment, pharmaceutical composition of the present invention is grouped into by following one-tenth:
According to one of embodiment, pharmaceutical composition of the present invention is grouped into by following one-tenth:
According to one of embodiment, pharmaceutical composition of the present invention is grouped into by following one-tenth:
The amount of maleic acid Flupirtine is the intensity of desired solid preparation and deciding.Preparation intensity can be 50 mg to 200mg, and wherein typical intensity is 50mg, 100mg, 200mg.
Another object of the present invention is to provide the preparation of drug combination that contains maleic acid Flupirtine method.
Method for preparing of the present invention may further comprise the steps:
1) with calcium hydrogen phosphate, cross 100 mesh sieves, subsequent use;
2) the maleic acid Flupirtine was pulverized 600 mesh sieves, subsequent use;
3) with maleic acid Flupirtine and calcium hydrogen phosphate and part silicon dioxide, magnesium stearate mix homogeneously;
4) above-mentioned gained material is put processed dry and hard material in the dry granulation machine, and smash and be dried granule through waving granulator;
5) the dried granule of gained is passed through 24 orders and 60 order stainless steel meshs successively, collect 60 eye mesh screen upper sections, be qualified granule;
6) adding adds the adjuvant polyvinylpolypyrrolidone in above-mentioned material, and remaining silica, magnesium stearate, mix homogeneously;
7) encapsulated;
Preferably, preparation process humidity is controlled at below 40%.
A purpose more of the present invention is to provide the application of pharmaceutical composition in the medicine of preparation treatment neuralgia, pain, headache and the postoperative pain relevant with degenerative arthritis.
Through following experiment, beneficial effect of the present invention is further explained.
Experiment one, prescription screening experiment
The solid, dry granule that pharmaceutical composition of the present invention comprises the maleic acid Flupirtine reaches pharmaceutically acceptable adjuvant.
1, diluent:
Capsule is formed said diluent and is included but not limited to lactose, pre-paying starch, microcrystalline Cellulose, calcium carbonate, calcium hydrogen phosphate, starch, glycine, sucrose, mannitol, preferably phosphoric acid hydrogen calcium.
2, disintegrating agent:
The dissolution contrast test of these article disintegrating agent capsule when investigating polyvinylpolypyrrolidone, corn starch, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose as disintegrating agent, preferred polyvinylpolypyrrolidone.
| Prescription | Dissolution |
| Low-substituted hydroxypropyl cellulose | 90.2%/91.2% |
| Carboxymethyl starch sodium | 90.3%/91.2% |
| Corn starch | 93.1%/92.3% |
| Polyvinylpolypyrrolidone | 99.7%/99.5% |
Can know that by table select the prescription polyvinylpolypyrrolidone, dissolution is good.
3, the selection of lubricant and fluidizer:
As preferred magnesium stearate is hydrophobic lubricant, is prone to and the granule mixing, adds silicon dioxide and reaches recess with particle surface and fill up and mend flatly, lowers the roughening of particle surface, is easy to and blank adjuvant mix homogeneously.Lubricant is to add before the tabletting, in order to reduce the adjuvant of frictional force between the granule punch die.Because of it has reduced the friction with punch die, can increase particulate flowability, make fill good.
Magnesium stearate: be white powder, fine and smooth loose, there is good tack after granule mixes, to be evenly distributed and should not separates, lubrication is good, has block resistance and unilateral smooth and beautiful appearance, is widely used.
Silicon dioxide: small particle diameter and bigger serface make it have the flowability of expectation, and these characteristics can be used for improving the flowability of dry powder in many processes, use mainly as fluidizer.
Through above-mentioned prescription screening, obtain the most preferred prescription of the present invention and form:
Experiment two, stability experiment
Experimental group: the embodiment of the invention 1
Matched group: the maleic acid Flupirtine capsule of selling on the market
Experimental result shows that maleic acid Flupirtine capsule of the present invention is at 25 ℃, and humidity is to preserve after 12 months under 60% condition still can keep very high content, and far above matched group, explains that the present invention has extraordinary stability compared with similar products.
Experiment three, dissolution experiment:
The capsule sample that removes photoresist takes by weighing calculated weight difference, and RSD is less, and stripping is more satisfactory.
RSD dissolution (30 minutes)
Preparation technology's characteristics of the present invention are, the maleic acid Flupirtine is processed the solid, dry granule, then with blank adjuvant parcel solid, dry granule; Make granule and ambient light according to isolating fully; And adopt the opaque capsule shell encapsulated, and solved the difficult problem of maleic acid Flupirtine illumination degrading well, make the stability of maleic acid Flupirtine obtain great enhancing; Be convenient to the product storage, transportation and use.Particularly, the particle diameter of composition and does not make the water equal solvent so that it has relative homogeneity in the control granule in the preparation process, makes it possible to produce the maleic acid Flupirtine solid preparation with very ideal storage stability.
The specific embodiment
Through following specific embodiment the present invention is further explained, but not as restriction.
Embodiment 1, maleic acid Flupirtine capsule prescription:
Technology:
1) with calcium hydrogen phosphate, cross 100 mesh sieves, subsequent use;
2) the maleic acid Flupirtine was pulverized 600 mesh sieves, subsequent use;
3) with maleic acid Flupirtine and calcium hydrogen phosphate and 10g silicon dioxide, 10g magnesium stearate mix homogeneously;
4) above-mentioned gained material is put processed dry and hard material in the dry granulation machine, and smash and be dried granule through waving granulator;
5) the dried granule of gained is passed through 24 orders and 80 order stainless steel meshs successively, collect 80 eye mesh screen upper sections, be qualified granule;
6) adding adds the adjuvant polyvinylpolypyrrolidone, 10g silicon dioxide, 3g magnesium stearate, mix homogeneously in above-mentioned material;
7) encapsulated.
Embodiment 2, maleic acid Flupirtine capsule prescription:
Technology:
1) with calcium hydrogen phosphate, cross 100 mesh sieves, subsequent use;
2) the maleic acid Flupirtine was pulverized 600 mesh sieves, subsequent use;
3) with maleic acid Flupirtine and calcium hydrogen phosphate and 10g silicon dioxide, 10g magnesium stearate mix homogeneously;
4) above-mentioned gained material is put processed dry and hard material in the dry granulation machine, and smash and be dried granule through waving granulator;
5) the dried granule of gained is passed through 24 orders and 80 order stainless steel meshs successively, collect 80 eye mesh screen upper sections, be qualified granule;
6) adding adds the adjuvant polyvinylpolypyrrolidone, 10g silicon dioxide, 3g magnesium stearate, mix homogeneously in above-mentioned material;
7) encapsulated.
Embodiment 3, maleic acid Flupirtine capsule prescription:
1) with calcium hydrogen phosphate, cross 100 mesh sieves, subsequent use;
2) the maleic acid Flupirtine was pulverized 600 mesh sieves, subsequent use;
3) with maleic acid Flupirtine and calcium hydrogen phosphate and 20g silicon dioxide, 20g magnesium stearate mix homogeneously;
4) above-mentioned gained material is put processed dry and hard material in the dry granulation machine, and smash and be dried granule through waving granulator;
5) the dried granule of gained is passed through 24 orders and 80 order stainless steel meshs successively, collect 80 eye mesh screen upper sections, be qualified granule;
6) adding adds the adjuvant polyvinylpolypyrrolidone, 20g silicon dioxide, 6g magnesium stearate, mix homogeneously in above-mentioned material;
7) encapsulated.
Embodiment 4, maleic acid Flupirtine capsule prescription:
Method for preparing is with embodiment 1.
Embodiment 5, maleic acid Flupirtine capsule prescription:
Method for preparing is with embodiment 1.
Claims (9)
1. a pharmaceutical composition that contains the maleic acid Flupirtine is characterized in that, is grouped into by following one-tenth:
2. pharmaceutical composition according to claim 1 is characterized in that, is grouped into by following one-tenth:
3. pharmaceutical composition according to claim 1 is characterized in that, is grouped into by following one-tenth:
4. pharmaceutical composition according to claim 1 is characterized in that, is grouped into by following one-tenth:
5. the arbitrary described pharmaceutical composition of claim 1-4 is a capsule.
6. the described preparation of drug combination method of claim 1 is characterized in that not may further comprise the steps:,
1) with calcium hydrogen phosphate, cross 100 mesh sieves, subsequent use;
2) the maleic acid Flupirtine was pulverized 600 mesh sieves, subsequent use;
3) with maleic acid Flupirtine and calcium hydrogen phosphate and part silicon dioxide, magnesium stearate mix homogeneously;
4) above-mentioned gained material is put processed dry and hard material in the dry granulation machine, and smash and be dried granule through waving granulator;
5) the dried granule of gained is passed through 24 orders and 60 order stainless steel meshs successively, collect 60 eye mesh screen upper sections, be qualified granule;
6) adding adds the adjuvant polyvinylpolypyrrolidone in above-mentioned material, and remaining silica, magnesium stearate, mix homogeneously;
7) encapsulated.
7. the described preparation of drug combination method of claim 2 is characterized in that step is following:
Prescription:
Technology:
1) with calcium hydrogen phosphate, cross 100 mesh sieves, subsequent use;
2) the maleic acid Flupirtine was pulverized 600 mesh sieves, subsequent use;
3) with maleic acid Flupirtine and calcium hydrogen phosphate and 10g silicon dioxide, 10g magnesium stearate mix homogeneously;
4) above-mentioned gained material is put processed dry and hard material in the dry granulation machine, and smash and be dried granule through waving granulator;
5) the dried granule of gained is passed through 24 orders and 80 order stainless steel meshs successively, collect 80 eye mesh screen upper sections, be qualified granule;
6) adding adds the adjuvant polyvinylpolypyrrolidone, 10g silicon dioxide, 3g magnesium stearate, mix homogeneously in above-mentioned material;
7) encapsulated.
8. the described preparation of drug combination method of claim 3 is characterized in that step is following:
Prescription:
Technology:
1) with calcium hydrogen phosphate, cross 100 mesh sieves, subsequent use;
2) the maleic acid Flupirtine was pulverized 600 mesh sieves, subsequent use;
3) with maleic acid Flupirtine and calcium hydrogen phosphate and 10g silicon dioxide, 10g magnesium stearate mix homogeneously;
4) above-mentioned gained material is put processed dry and hard material in the dry granulation machine, and smash and be dried granule through waving granulator;
5) the dried granule of gained is passed through 24 orders and 80 order stainless steel meshs successively, collect 80 eye mesh screen upper sections, be qualified granule;
6) adding adds the adjuvant polyvinylpolypyrrolidone, 10g silicon dioxide, 3g magnesium stearate, mix homogeneously in above-mentioned material;
7) encapsulated.
9. the described preparation of drug combination method of claim 4 is characterized in that step is following:
Prescription:
1) with calcium hydrogen phosphate, cross 100 mesh sieves, subsequent use;
2) the maleic acid Flupirtine was pulverized 600 mesh sieves, subsequent use;
3) with maleic acid Flupirtine and calcium hydrogen phosphate and 20g silicon dioxide, 20g magnesium stearate mix homogeneously;
4) above-mentioned gained material is put processed dry and hard material in the dry granulation machine, and smash and be dried granule through waving granulator;
5) the dried granule of gained is passed through 24 orders and 80 order stainless steel meshs successively, collect 80 eye mesh screen upper sections, be qualified granule;
6) adding adds the adjuvant polyvinylpolypyrrolidone, 20g silicon dioxide, 6g magnesium stearate, mix homogeneously in above-mentioned material;
7) encapsulated.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012103217340A CN102836156A (en) | 2012-09-03 | 2012-09-03 | Capsule containing flupirtine maleate and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012103217340A CN102836156A (en) | 2012-09-03 | 2012-09-03 | Capsule containing flupirtine maleate and preparation method thereof |
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| CN102836156A true CN102836156A (en) | 2012-12-26 |
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| CN2012103217340A Pending CN102836156A (en) | 2012-09-03 | 2012-09-03 | Capsule containing flupirtine maleate and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104083335A (en) * | 2013-07-31 | 2014-10-08 | 成都苑东药业有限公司 | Flupirtine maleate capsule composition and preparation method thereof |
| CN107412186A (en) * | 2017-08-02 | 2017-12-01 | 瑞阳制药有限公司 | composition containing flupirtine maleate and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1838955A (en) * | 2003-06-23 | 2006-09-27 | 卡尔－格奥尔格·施密特 | Flupirtine preparation for treating neurodegenerative disorders of the visual system and diabetes mellitus |
-
2012
- 2012-09-03 CN CN2012103217340A patent/CN102836156A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1838955A (en) * | 2003-06-23 | 2006-09-27 | 卡尔－格奥尔格·施密特 | Flupirtine preparation for treating neurodegenerative disorders of the visual system and diabetes mellitus |
Non-Patent Citations (8)
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| AWD公司: "科达得龙中国包装", 《科达得龙药品包装》, 12 September 2006 (2006-09-12) * |
| AWD公司: "科达得龙产品信息", 《科达得龙产品信息》, 12 September 2006 (2006-09-12) * |
| 周宇宇: "氟吡汀的制备和其晶型转变及三氨基吡啶化合物的合成研究", 《中国优秀硕士学位论文全文数据库（电子期刊）》, no. 8, 15 August 2006 (2006-08-15), pages 014 - 74 * |
| 国家药品食品监督管理总局: "科达得龙产品", 《中国药品注册数据库》, 12 September 2006 (2006-09-12) * |
| 国家食品药品监督管理总局: "科达得龙产品信息", 《国家食品药品监督管理总局-数据查询》, 29 May 2012 (2012-05-29) * |
| 李绍贤等: "马来酸氟吡汀胶囊与进口产品溶出曲线相似性的比较", 《安徽医药》, vol. 15, no. 12, 31 December 2011 (2011-12-31), pages 1493 - 1496 * |
| 毕殿洲: "《药剂学》", 28 February 2003, article "胶囊剂" * |
| 闫晓娟: "科达得龙价格说明书科达得龙功能主治", 《HTTP://WWW.KMFXX.CN/D2327096/》, 11 July 2011 (2011-07-11) * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104083335A (en) * | 2013-07-31 | 2014-10-08 | 成都苑东药业有限公司 | Flupirtine maleate capsule composition and preparation method thereof |
| CN107412186A (en) * | 2017-08-02 | 2017-12-01 | 瑞阳制药有限公司 | composition containing flupirtine maleate and preparation method thereof |
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Application publication date: 20121226 |