CN101862326B - Medicine compound containing febuxostat - Google Patents
Medicine compound containing febuxostat Download PDFInfo
- Publication number
- CN101862326B CN101862326B CN2009100822522A CN200910082252A CN101862326B CN 101862326 B CN101862326 B CN 101862326B CN 2009100822522 A CN2009100822522 A CN 2009100822522A CN 200910082252 A CN200910082252 A CN 200910082252A CN 101862326 B CN101862326 B CN 101862326B
- Authority
- CN
- China
- Prior art keywords
- febuxostat
- pharmaceutical composition
- preparation
- binding agent
- surfactant
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Abstract
The invention discloses a medicine compound containing febuxostat; and containing the febuxostat and surfactant, the medicine compound can be stably and quickly dissolved out and is applicable to arthrolithiasis curing.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition that contains Febuxostat, be applicable to treat the too high disease of uric acid.Especially the preparation that utilizes the special additive enhanced stability and prepare with short grained Febuxostat, have stable, good dissolution, can guarantee that active component discharges fast fully.
Background technology
Gout is too much to reach the decline of kidney removing ability owing to producing uric acid in body, and uric acid is accumulated in vivo, causes urate crystal in joint and each internal organs precipitation.Clinical treatment gout medicine mainly is divided into the promotion urate excretion and suppresses uricopoiesis at present, and adopts adequate measure to improve related symptoms.Along with the raising of living standards of the people, be mainly that the proportion of various animal foods in dietary structure increases gradually, make original rare prevalence of gout was grow with each passing day.How to develop a kind of effectively, the medicine of safety and taking convenience become to continue the problem solved.In decades, allopurinol be clinically unique one for suppressing the medicine of uricopoiesis, and be widely used in clinical as the gold medicine of gout, but need to repeat heavy dose of administration and maintain higher levels of drugs, cause the serious even fatal untoward reaction due to drug accumulation simultaneously.
Febuxostat (Febuxostat) is novel non-purines XOR enzyme inhibitor, it has the selectivity of height to XOR, can reduce uricopoiesis, the patient who the overwhelming majority is suffered to gout and hyperuricemia is effective, can make serum uric acid level descend and be stabilized in below 6.0mg/dl, reducing gouty attack,acute.Febuxostat, than allopurinol, has very high selectivity, safety and stronger activity.
Yet Febuxostat is insoluble drug, provide a kind of stable, the preparation that improves bioavailability is most important.The patent of CN03806919 discloses a kind of solid preparation that contains single crystal form, mentions the most stable crystal formation of use and also can't obtain the preparation that the stripping curve deviation is little.Difference on dissolution rate directly causes the time of active component onset.
Therefore, find effective approach, provide a kind of stable, stripping Febuxostat preparation rapidly is very urgent.
Summary of the invention
The applicant finds by reducing the particle diameter of Febuxostat unexpectedly, can improve its dissolution bioavailability, and obtain good dissolving out capability.The applicant finds can make by adding a small amount of surfactant the rapid stripping of Febuxostat preparation stabilization simultaneously.
A kind of pharmaceutical composition that contains Febuxostat, contain Febuxostat and surfactant.
In pharmaceutical composition disclosed by the invention, Febuxostat is crystal form, its X-ray powder diffraction pattern is 6.80 ± 0.2,10.04 ± 0.2,11.00 ± 0.2 at 2 θ, 13.56 ± 0.2,15.72 ± 0.2,17.60 ± 0.2,20.34 ± 0.2,22.08 ± 0.2,23.72 ± 0.2,24.72 ± 0.2,25.34 ± 0.2.
Pharmaceutical composition disclosed by the invention, the particle diameter of Febuxostat (D90) is less than 150 microns.
Pharmaceutical composition disclosed by the invention, containing Febuxostat 80mg or 120mg.
Pharmaceutical composition disclosed by the invention, further contain one or more pharmaceutically acceptable carriers that are selected from filler, diluent, disintegrating agent, lubricant, binding agent, fluidizer and chelating agen.
Pharmaceutical composition disclosed by the invention, surfactant contains one or more in tween 80, sodium lauryl sulphate, Myrj 52, polyoxyethylene castor oil glycerin ether.
Pharmaceutical composition disclosed by the invention, surfactant is that the mode with binding agent or wetting agent adds.
Pharmaceutical composition disclosed by the invention is tablet form.
The specific embodiment
Below in conjunction with embodiment, the present invention is described in further detail, but be not limited to following embodiment.
Embodiment 1
Preparation method:
PVP K30, tween 80 are dissolved in to a certain amount of ethanol, as binding agent; By the Febuxostat of recipe quantity and lactose, microcrystalline Cellulose hyprolose, add above-mentioned binding agent after mixing, stir preparation; Dryly under 40-60 ℃ of temperature conditions must do granule; By dry granule, use the pelletizing machine granulate, and add magnesium stearate, tabletting, 15% Opadry aqueous dispersion coating, packing, obtain.
Embodiment 2
Preparation method:
SDS is dissolved in to a certain amount of hot water, adds starch, make 10% starch slurry, as binding agent; By the Febuxostat of recipe quantity and lactose, microcrystalline Cellulose, hyprolose, add above-mentioned binding agent after mixing, stir preparation; Dryly under 40-60 ℃ of temperature conditions must do granule; By dry granule granulate, and add magnesium stearate, tabletting, 15% Opadry aqueous dispersion coating, packing, obtain.
Embodiment 3
Preparation method:
Polyoxyethylene castor oil glycerin ether (Cremophore EL) is dissolved in to a certain amount of purified water, as wetting agent; By the Febuxostat of recipe quantity and lactose, microcrystalline Cellulose, cross-linked carboxymethyl cellulose sodium, add above-mentioned wetting agent after mixing, stir preparation; Dryly under 40-60 ℃ of temperature conditions must do granule; By dry granule granulate, and add magnesium stearate, tabletting, 15% Opadry aqueous dispersion coating, packing, obtain.
Embodiment 4
Preparation method:
Myrj 52 is dissolved in to a certain amount of purified water, as wetting agent; By the Febuxostat of recipe quantity and lactose, microcrystalline Cellulose, cross-linked carboxymethyl cellulose sodium, add above-mentioned wetting agent after mixing, stir preparation; Dryly under 40-60 ℃ of temperature conditions must do granule; By dry granule, use the pelletizing machine granulate, and add magnesium stearate, tabletting, 15% Opadry aqueous dispersion coating, packing, obtain.
Annotate: the Febuxostat used in embodiment 1-4 example is the X crystal formation, and through micronization processes, D90 is less than 150 microns.
Embodiment 5
Preparation method:
SDS is dissolved in to a certain amount of hot water, adds starch, make 10% starch slurry, as binding agent; By the Febuxostat of recipe quantity and lactose, microcrystalline Cellulose, hyprolose, add above-mentioned binding agent after mixing, stir and granulate; Dryly under 40-60 ℃ of temperature conditions must do granule; By dry granule granulate, and add magnesium stearate, tabletting, 15% Opadry aqueous dispersion coating, packing, obtain.
Embodiment 6
Preparation method:
Prepare 10% starch slurry, as binding agent; By the Febuxostat of recipe quantity and lactose, microcrystalline Cellulose, hyprolose, SDS, add above-mentioned binding agent after mixing, stir and granulate; Dryly under 40-60 ℃ of temperature conditions must do granule; By dry granule granulate, and add magnesium stearate, tabletting, 15% Opadry aqueous dispersion coating, packing, obtain.
Embodiment 7
Preparation method:
Prepare 10% starch slurry, as binding agent; By the Febuxostat of recipe quantity and lactose, microcrystalline Cellulose, hyprolose, add above-mentioned binding agent after mixing, stir and granulate; Dryly under 40-60 ℃ of temperature conditions must do granule; By dry granule granulate, and add magnesium stearate, tabletting, 15% Opadry aqueous dispersion coating, packing, obtain.
Embodiment 8
Embodiment 1-4 and comparative example 1-3 are put under (75% ± 5%, 40 ℃ ± 2 ℃) condition, carry out the primary stability investigation, and dissolution while checking 15min (the oar method, 900ml, water, 50 turn).The results are shown in following table.
| Dissolution % | 0 day | Accelerate January | Accelerate February | Accelerate March | Accelerate June |
| Embodiment 1 | ?96.23±1.04 | ?97.96±2.00 | ?98.08±1.35 | ?99.25±1.43 | ?99.07±1.96 |
| Embodiment 2 | ?98.93±1.10 | ?98.51±1.27 | ?98.93±1.70 | ?99.54±1.29 | ?98.53±1.07 |
| Embodiment 3 | ?97.85±1.38 | ?100.3±1.47 | ?98.27±1.66 | ?98.35±1.89 | ?98.12±1.23 |
| Embodiment 4 | ?99.02±1.57 | ?98.44±2.08 | ?100.0±1.09 | ?98.69±1.76 | ?97.99±1.64 |
| The comparative example 1 | ?78.36±3.06 | ?76.48±5.32 | ?71.65±5.35 | ?68.56±4.14 | ?64.34±5.06 |
| The comparative example 2 | ?73.89±2.88 | ?72.36±3.93 | ?70.84±6.36 | ?63.30±6.26 | ?55.89±4.88 |
| The comparative example 3 | ?65.56±3.62 | ?63.15±4.29 | ?60.97±4.42 | ?54.56±4.61 | ?52.56±5.62 |
Therefore, from the result shown in table, can find out, the Febuxostat sheet stripping that compositions of the present invention provides is relatively stable, and rapidly, other every assays also prove that the preparation prepared by said composition is very stable simultaneously, are therefore a kind of good preparations.
Claims (4)
1. a pharmaceutical composition that contains Febuxostat, is characterized in that containing Febuxostat and surfactant; Described Febuxostat is crystal form, and its X-ray powder diffraction pattern is 6.80 ± 0.2,10.04 ± 0.2,11.00 ± 0.2 at 2 θ, 13.56 ± 0.2,15.72 ± 0.2,17.60 ± 0.2,20.34 ± 0.2,22.08 ± 0.2,23.72 ± 0.2,24.72 ± 0.2,25.34 ± 0.2; Its D90 particle diameter is less than 150 microns; Described surfactant is one or more in tween 80, sodium lauryl sulphate, Myrj 52, polyoxyethylene castor oil glycerin ether.
2. pharmaceutical composition as claimed in claim 1, is characterized in that containing Febuxostat 80mg or 120mg.
3. pharmaceutical composition as claimed in claim 1, is characterized in that containing one or more pharmaceutically acceptable carriers that are selected from filler, diluent, disintegrating agent, lubricant, binding agent, fluidizer and chelating agen.
4. pharmaceutical composition as claimed in claim 1, is characterized in that for tablet form.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100822522A CN101862326B (en) | 2009-04-20 | 2009-04-20 | Medicine compound containing febuxostat |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100822522A CN101862326B (en) | 2009-04-20 | 2009-04-20 | Medicine compound containing febuxostat |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101862326A CN101862326A (en) | 2010-10-20 |
| CN101862326B true CN101862326B (en) | 2013-12-04 |
Family
ID=42954387
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009100822522A Active CN101862326B (en) | 2009-04-20 | 2009-04-20 | Medicine compound containing febuxostat |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101862326B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102488665B (en) * | 2011-12-15 | 2013-03-06 | 宁夏康亚药业有限公司 | Febuxostat tablet and preparation method thereof |
| CN102895210B (en) * | 2011-12-15 | 2014-08-06 | 宁夏康亚药业有限公司 | Febuxostat tablet with improved dissolution rate |
| CN102895209B (en) * | 2011-12-15 | 2013-12-25 | 宁夏康亚药业有限公司 | Febuxostat tablet |
| CN102614146B (en) * | 2012-04-28 | 2013-06-12 | 杭州朱养心药业有限公司 | Method for preparing febuxostat tablet and febuxostat tablet |
| CN102614145B (en) * | 2012-04-28 | 2013-05-01 | 杭州朱养心药业有限公司 | Stable febuxostat tablet and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1954814A (en) * | 2005-10-26 | 2007-05-02 | 重庆医药工业研究院有限责任公司 | Medical composite with co-action for treating gout and its preparation method |
| CN1970547A (en) * | 2006-12-07 | 2007-05-30 | 重庆医药工业研究院有限责任公司 | Novel febuxostat crystal form and its preparation method |
| CN101780073A (en) * | 2009-01-21 | 2010-07-21 | 重庆圣华曦药业有限公司 | Febuxostat dispersible tablet drug and preparing method thereof |
-
2009
- 2009-04-20 CN CN2009100822522A patent/CN101862326B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1954814A (en) * | 2005-10-26 | 2007-05-02 | 重庆医药工业研究院有限责任公司 | Medical composite with co-action for treating gout and its preparation method |
| CN1970547A (en) * | 2006-12-07 | 2007-05-30 | 重庆医药工业研究院有限责任公司 | Novel febuxostat crystal form and its preparation method |
| CN101780073A (en) * | 2009-01-21 | 2010-07-21 | 重庆圣华曦药业有限公司 | Febuxostat dispersible tablet drug and preparing method thereof |
Non-Patent Citations (4)
| Title |
|---|
| 《新药快递》;医药快讯;《中国执业药师》;20090401;第54页 * |
| 医药快讯.《新药快递》.《中国执业药师》.2009,第54页. |
| 唐春雷等.新型抗痛风药物非布索坦.《中国新药杂质》.2009,第18卷(第7期),第577-581页. |
| 新型抗痛风药物非布索坦;唐春雷等;《中国新药杂质》;20090415;第18卷(第7期);第577-581页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101862326A (en) | 2010-10-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3417861B1 (en) | Pharmaceutical composition containing jak kinase inhibitor or pharmaceutically acceptable salt thereof | |
| CN102631347B (en) | Gefinitib medicinal composite and method for preparing same | |
| TW492878B (en) | Tablet composition | |
| CN101862326B (en) | Medicine compound containing febuxostat | |
| KR101712524B1 (en) | Combinatory formulation comprising tadalafil and dutasteride and the method for preparing thereof | |
| BRPI0713565B1 (en) | process for making a solid oral dosage form | |
| CN103550165A (en) | Medicinal composition containing rivaroxaban and preparation method thereof | |
| AU2011247642C1 (en) | Orally disintegrating tablet containing acarbose | |
| WO2011160541A1 (en) | Tolvaptan solid dispersion and its preparation method | |
| CN1143908A (en) | Treatment of diabetic nephropathy with valsartan | |
| EP2359816B1 (en) | Aripiprazole formulations | |
| CN101485659A (en) | Medicament composition of amlodipine and simvastatin as well as preparation method and application thereof | |
| EP2515849A1 (en) | Effervescent tablet and granule formulation comprising cefixime | |
| CN102670537B (en) | Trimetazidine dihydrochloride sustained release tablet and preparation method thereof | |
| JP5476782B2 (en) | Method for producing arginine-containing tablets | |
| CN102451171B (en) | Tindazole vaginal effervescent tablet and preparation method thereof | |
| EP2925320B1 (en) | Novel method for improving the bioavailability of low aqueous solubility drugs | |
| RU2007147953A (en) | PHARMACEUTICAL RECIPES OF MICRONIZED (4-CHLOROPHENYL) [4- (4-pyridylmethyl) -phthalazin-1-yl] AND ITS SALTS WITH IMMEDIATE EXCESSION AND HIGH CONTENT | |
| CN1762354A (en) | Stable pharmaceutical composition containing calcium blocker | |
| EP3154525B1 (en) | Pharmaceutical composition comprising a triazole antifungal agent and method for preparation thereof | |
| EP4317156A1 (en) | Injectable lurasidone suspension and preparation method therefor | |
| CN101152142A (en) | Solid pharmaceutical composition containing 2-(3-cyano-4- isobutoxy phenyl)-4-methyl-5-thiazole methanoic acid | |
| WO2000037083A1 (en) | Oral antiestrogen pharmaceutical composition | |
| CN117653608A (en) | Stable quick-release tablet and preparation method thereof | |
| CN117338724A (en) | Phloroglucinol release-regulating preparation and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20210119 Address after: 570314 no.279 Nanhai Avenue, Xiuying District, Haikou City, Hainan Province Patentee after: AVENTIS PHARMA (HAINAN) Co.,Ltd. Address before: 100097, Wanquan mansion, 3 Jin Zhuang, Haidian District, Beijing, Sijiqing Patentee before: BEIJING D-VENTUREPHARM TECHNOLOGY DEVELOPMENT Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| DD01 | Delivery of document by public notice |
Addressee: Song Xuemei Document name: Notice of conformity |
|
| DD01 | Delivery of document by public notice |