CN101085761A - Febuxotat microcrystal and compositions thereof - Google Patents
Febuxotat microcrystal and compositions thereof Download PDFInfo
- Publication number
- CN101085761A CN101085761A CN 200710043178 CN200710043178A CN101085761A CN 101085761 A CN101085761 A CN 101085761A CN 200710043178 CN200710043178 CN 200710043178 CN 200710043178 A CN200710043178 A CN 200710043178A CN 101085761 A CN101085761 A CN 101085761A
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- Prior art keywords
- febuxotat
- microcrystal
- composition
- fei
- butate
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- 239000000203 mixture Substances 0.000 title claims description 20
- 239000013081 microcrystal Substances 0.000 title claims description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 27
- 238000002360 preparation method Methods 0.000 claims abstract description 27
- 239000007787 solid Substances 0.000 claims description 12
- 239000002775 capsule Substances 0.000 claims description 8
- 239000002245 particle Substances 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 238000009472 formulation Methods 0.000 claims description 6
- 239000000843 powder Substances 0.000 claims description 6
- 238000002050 diffraction method Methods 0.000 claims description 5
- 238000001228 spectrum Methods 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 4
- 238000001953 recrystallisation Methods 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 229910002483 Cu Ka Inorganic materials 0.000 claims 1
- 238000002425 crystallisation Methods 0.000 abstract description 15
- 230000008025 crystallization Effects 0.000 abstract description 14
- 238000000034 method Methods 0.000 abstract description 3
- 231100000252 nontoxic Toxicity 0.000 abstract description 2
- 230000003000 nontoxic effect Effects 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract 1
- 235000019439 ethyl acetate Nutrition 0.000 abstract 1
- 229940126589 solid medicine Drugs 0.000 abstract 1
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
- 238000004090 dissolution Methods 0.000 description 12
- 239000013078 crystal Substances 0.000 description 7
- 235000019359 magnesium stearate Nutrition 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000009826 distribution Methods 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000000113 differential scanning calorimetry Methods 0.000 description 3
- 239000010419 fine particle Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 229910017488 Cu K Inorganic materials 0.000 description 2
- 229910017541 Cu-K Inorganic materials 0.000 description 2
- 239000004278 EU approved seasoning Substances 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 235000011194 food seasoning agent Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 239000011122 softwood Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000002798 spectrophotometry method Methods 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 229940032147 starch Drugs 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000002411 thermogravimetry Methods 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 229920003081 Povidone K 30 Polymers 0.000 description 1
- 229940123769 Xanthine oxidase inhibitor Drugs 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 238000004455 differential thermal analysis Methods 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- BQSJTQLCZDPROO-UHFFFAOYSA-N febuxostat Chemical group C1=C(C#N)C(OCC(C)C)=CC=C1C1=NC(C)=C(C(O)=O)S1 BQSJTQLCZDPROO-UHFFFAOYSA-N 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical class OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000008201 pharmaceutical excipient composition Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000007962 solid dispersion Substances 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 235000020985 whole grains Nutrition 0.000 description 1
- 239000003064 xanthine oxidase inhibitor Substances 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The invention discloses a natural non-buta crystallite which is characterized by fine grain size and good dissloving degree and its compound. Said crystallite is prepared through disslovant crystallization, and said disslovatn is non- toxic acetic ester. The invention is characterized in that the product is safe, the preparation method is more environment- friendly, and the micronizing or other extra treatment for process preparing solid medicine and turbid liquor are avoided.
Description
Technical field
The present invention relates to specific a kind of polymorphous medicinal compositions of Fei Butate (febuxotat), more specifically be meant a kind of crystal type of Fei Butate, this crystal type is natural to have fine particle size, be fit to form composition, be used to make oral solid formulation with good dissolution rate with conventional pharmaceutical excipient.
Background technology
The chemical structure of Fei Butate is 2-(3-cyano-4-isobutoxy phenyl)-4-methyl-5-thiazole carboxylic acid, is a kind of xanthine oxidase inhibitor, is used for the treatment of gout.
Because the solubleness of Fei Butate in water is little, there is the problem of dissolution rate difference in the oral solid formulation that contains this activeconstituents.And the granularity of activeconstituents and polymorphic are the important factors that influences the solid preparation dissolution rate.As document 1[Chinese invention patent publication number CN 1275126A] disclosed, Fei Butate has polymorphic.Document 2[Chinese invention patent publication number CN 1642546A for another example] further specify Fei Butate different crystal types when being prepared into solid preparation such as tablet, the dissolution rate of crystal formation and granularity remarkably influenced preparation.This invention is pointed out, needs elite wherein a kind of crystal form A that crystallizes out from methyl alcohol, carries out the solid preparation that micronization processing just can be prepared into good dissolution rate afterwards.Perhaps as document 3[Chinese invention patent publication number CN 1785182A] take solid dispersion technology, with the polyvinylpyrrolidone vitreous state sosoloid of preparing carriers Fei Butate, be used to make solid preparation, to obtain suitable dissolution rate.
The present invention discloses a kind of natural Fei Butatexin crystalline form with fine particle size, do not need micronization processing during as the manufacturing oral solid formulation, do not need to be prepared into vitreous state sosoloid yet, but directly add auxiliary material routinely technology can make the match in excellence or beauty dissolution rate of document 2 defined micronization A crystalline substances of dissolution rate.Therefore the composition of this crystallite and pharmaceutical excipient composition has in the medicament manufacturing and is easy to the advantage of processing significantly.
Summary of the invention
The object of the invention provides a kind of natural fine particle size that has, and has the Fei Butate crystallization of good dissolution rate, is called Febuxotat microcrystal.This crystallite does not need micronization processing or other extra processing in preparation medical solid preparation and suspensoid process, make conventional manufacturing process can make the good preparation of dissolution rate.The present invention also provides the composition of being made up of above-mentioned Febuxotat microcrystal and conventional pharmaceutical excipient.
The preparation of solvent crystallization method is adopted in crystallization of the present invention, does not need to make solvent with toxic compounds such as methyl alcohol, only needs nontoxic a kind of solvent of ethyl acetate to get final product.The product that makes is safer, and the preparation method is friendly more to environment simultaneously.
Crystallization of the present invention by using the x-ray diffractogram of powder spectrum of Cu-K α radiation detection, when representing with reflection angle 2 θ, locates to have characteristic peak being about 5.78 °, 7.94 °, 11.60 °, 12.72 °, 20.50 °, 25.88 °.Reasonably can be characterized by: crystallization of the present invention, by using the x-ray diffractogram of powder spectrum of Cu-K α radiation detection, when representing, has characteristic peak at the powder X-ray RD spectrum place of the combination of 5.8 ° ± 0.1 °, 7.9 ° ± 0.1 °, 11.6 ° ± 0.1 °, 12.7 ° ± 0.1 °, 20.5 ° ± 0.1 °, 25.9 ° ± 0.1 ° and/or wherein any or they with reflection angle 2 θ.
Crystallization of the present invention has basically the infrared spectrophotometric determination absorption spectrum of Fourier Tranform as shown in Figure 2.Adopt the KBr compressing tablet during mensuration.
Crystallization of the present invention is measured size-grade distribution with laser diffractometry, and each is added up particle diameter and has following feature: average diameter is less than 20 μ m, D
90Less than 40 μ m.
The hot analytical characteristic of crystalline of the present invention, when the differential scanning calorimetry, can characterize by near near two endothermic transition peaks that are characterized as 201 ℃ and 210 ℃, shown in the heat culvert-temperature variation curve of differential scanning calorimetry in the accompanying drawing 3, two endotherm(ic)peaks of 201.4 ℃ and 210.3 ℃.Weight-temperature variation curve is measured when carrying out thermogravimetric analysis in the accompanying drawing 3, and showing does not have recrystallisation solvent to exist.
Crystalline preparation method of the present invention: any crystal formation or armorphous Fei Butate, with ethyl acetate is solvent, heating makes dissolving, naturally cool to room temperature, or the temperature that reduces solution rapidly to room temperature or lower temperature such as 0 ℃, promptly separate out crystallization, filter, drying promptly gets the crystal type that the present invention discloses.Crystalline preparation method characteristic of the present invention is to use ethyl acetate to be solvent.
The conventional required pharmaceutical excipient of solid preparation is added in crystallization of the present invention, is prepared into tablet, pill, powder, capsule or dry suspensoid, and containing crystalline amount of the present invention in the unit preparation is 40mg, 80mg or 120mg.With the weight percent meter of crystallization of the present invention in unit formulation, be 1～50%, be 10～30% more specifically.Auxiliary material can be weighting agent lactose, N.F,USP MANNITOL, starch etc., disintegrating agent low-substituted hydroxypropyl cellulose, Microcrystalline Cellulose, sodium starch glycolate, polyvinylpolypyrrolidone, croscarmellose sodium, dry starch etc., tamanori polyvidone, Vltra tears, being prepared into the aqueous solution and using, also can be water; Lubricant is a Magnesium Stearate.
Because the granularity that this crystallite possesses itself makes it have good dissolution rate in aqueous systems.
Description of drawings
The crystalline x-ray diffractogram of powder spectrum of Fig. 1, embodiment 1 preparation.
The infrared IR collection of illustrative plates of the crystalline Fourier Tranform of Fig. 2, embodiment 1 preparation.
The crystalline thermogravimetric analysis and the differential scanning calorimetry figure of Fig. 3, embodiment 1 preparation.
The size distribution curve that the crystallization of Fig. 4, embodiment 1 preparation is measured with laser diffractometry.
The size distribution curve that the crystallization of Fig. 5, embodiment 2 preparations is measured with laser diffractometry.
Embodiment
Only the present invention will be described for example of the present invention, do not limit the invention.
Embodiment 1:
The extraordinarily thick product 100g of Fei Buta, ethyl acetate 1400ml are added in the 3L round-bottomed flask, be warming up to backflow, be stirred to complete molten after, filtered while hot, filtrate placement naturally cools to room temperature, crystallization filters, and filter cake washs with a spot of ethyl acetate, in 80 ℃ of vacuum-dryings 4 hours, get solid 82.6g, mp198.7～201.4 ℃ (differential thermal analysis is measured, and sees Fig. 3).
Powder x-ray diffraction analysis: collection of illustrative plates is seen Fig. 1; Locate to have characteristic peak at 5.78 °, 7.94 °, 11.60 °, 12.72 °, 20.50 °, 25.88 °.
IR analyzes: the infrared IR collection of illustrative plates of Fourier Tranform is seen Fig. 2.
Sreen analysis: particle size distribution figure is seen Fig. 4; Statistics particle diameter D
102.779 μ m, D
5011.24 μ m, D
9038.14 μ m, average diameter 16.73 μ m.
Embodiment 2:
The extraordinarily thick product 100g of Fei Buta, ethyl acetate 2000ml are added in the 5L round-bottomed flask, be warming up to backflow, be stirred to complete molten after, filtered while hot, filtrate are positioned in 0 ℃ the ice-water bath cools off crystallization, filter, filter cake washs with a spot of ethyl acetate, in 80 ℃ of vacuum-dryings 4 hours, gets solid 88.4g.
Sreen analysis: adopt laser diffractometry to measure particle size distribution figure and see Fig. 5; Statistics particle diameter D
101.160 μ m, D
5010.36 μ m, D
9036.03 μ m, average diameter 15.07 μ m.
Embodiment 3:
The capsule preparation.
The crystallite 40g of embodiment 1 preparation
Pharmaceutical lactose 90g
Pregelatinized Starch 30g
Carboxymethylstach sodium 12g
Magnesium Stearate 1g
Make 1000 altogether
Preparation technology: the component in will writing out a prescription beyond the Magnesium Stearate mixes, with the aqueous solution that contains 3% (w/w) 30 POVIDONE K 30 BP/USP 29/31 in right amount is tackiness agent, make softwood, extruding becomes wet granular with crossing 14 mesh sieves, puts 80 ℃ of air seasonings 2 hours, and dried particle is by the whole grain of 14 mesh sieves, add remaining Magnesium Stearate, mix, be filled in gelatine capsule No. 2, promptly.
Embodiment 4:
The preparation of tablet.
The crystallite 40g of embodiment 2 preparations
Pharmaceutical lactose 160g
Microcrystalline Cellulose PH101 45g
Low-substituted hydroxypropyl methylcellulose 15g
Carboxymethylstach sodium 15g
Magnesium Stearate 2g
Make 500 altogether
Preparation technology: get carboxymethylstach sodium and Magnesium Stearate component in addition and mix, water is that tackiness agent is made softwood, promptly presses by 14 mesh sieves to become wet granular, put 80 ℃ of air seasonings 2 hours, make dried particle after, add carboxymethylstach sodium and Magnesium Stearate and mix, compressing tablet, promptly.Record hardness 5-7kg with tablet four-function instrument.
Embodiment 5:
Determination of dissolution rate: get each 6 or 6 of capsule that embodiment 3 and 4 makes and sheets respectively, measure respectively according to dissolution method [Chinese Pharmacopoeia version in 2005 two appendix X C (second method)].With pH5.5 McIlvaine buffered soln 1000ml is solvent (getting 0.1M citric acid solution 435.5ml mixes promptly with 0.2M disodium phosphate soln 564.5ml), and rotating speed is 50rpm, in accordance with the law operation.Respectively at 5,10,15,30,45, the 60min sampling, adopt ultraviolet spectrophotometry to measure at 317nm, the results are shown in following table:
The average stripping quantity of sheet and capsule (%) (N=6)
| Formulation | Sampling time (min) | |||||
| 5 | 10 | 15 | 30 | 45 | 60 | |
| Tablet | 37.6 | 65.1 | 81.2 | 91.1 | 94.6 | 95.9 |
| Capsule | 26.5 | 60.9 | 82.1 | 92.8 | 95.7 | 96.3 |
The result shows, reaches 80% through the solubility rate of 15 fens time-cards and capsule, through 45 minutes near all strippings.
Claims (6)
1, a kind ofly absorbs feature as characterizing, adopt laser diffractometry to measure statistics particle diameter D with powder X-ray RD spectrum place in the combination of 5.8 ° ± 0.1 °, 7.9 ° ± 0.1 °, 11.6 ° ± 0.1 °, 12.7 ° ± 0.1 °, 20.5 ° ± 0.1 °, 25.9 ° ± 0.1 ° and/or wherein any or they by the Cu-Ka radiating
90＜40 microns, the Febuxotat microcrystal of average diameter＜20 micron sign.
2, Febuxotat microcrystal according to claim 1 is characterized in that described Febuxotat microcrystal is that solvent carries out recrystallization operation acquisition with the ethyl acetate.
3, a kind of Fei Butate composition of forming by described Febuxotat microcrystal of claim 1 and conventional pharmaceutical excipient.
4, the composition of Febuxotat microcrystal according to claim 3 is characterized in that said composition is used to prepare oral solid formulation, tablet and capsule.
5, the composition of Febuxotat microcrystal according to claim 3, the prescription consumption that it is characterized in that Febuxotat microcrystal is by weight 10～30%.
6, the composition of Febuxotat microcrystal according to claim 3, the amount that it is characterized in that containing in the unit preparation of prescription of Fei Butate Fei Butate is 40mg, 80mg or 120mg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2007100431784A CN100546985C (en) | 2007-06-29 | 2007-06-29 | Febbutate microcrystal and its composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2007100431784A CN100546985C (en) | 2007-06-29 | 2007-06-29 | Febbutate microcrystal and its composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101085761A true CN101085761A (en) | 2007-12-12 |
| CN100546985C CN100546985C (en) | 2009-10-07 |
Family
ID=38936952
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2007100431784A Expired - Fee Related CN100546985C (en) | 2007-06-29 | 2007-06-29 | Febbutate microcrystal and its composition |
Country Status (1)
| Country | Link |
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Cited By (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010083752A1 (en) * | 2009-01-20 | 2010-07-29 | 重庆医药工业研究院有限责任公司 | High-purity febuxostat and the method for preparation |
| CN101817801A (en) * | 2009-08-12 | 2010-09-01 | 北京红惠新医药科技有限公司 | Preparation method of new crystal form K of 2-(3-cyano-4-isobutoxy)-4-methyl-5-thiazole formic acid and other crystal forms |
| CN101824005A (en) * | 2010-04-27 | 2010-09-08 | 上海凯米侬医药科技有限公司 | New crystal form Q of Febuxostat and preparation method thereof |
| WO2010144685A1 (en) | 2009-06-10 | 2010-12-16 | Teva Pharmaceutical Industries Ltd. | Crystalline forms of febuxostat |
| WO2011080651A2 (en) | 2009-12-31 | 2011-07-07 | Ranbaxy Laboratories Limited | Polymorphic forms of febuxostat |
| WO2011107911A1 (en) | 2010-03-04 | 2011-09-09 | Ranbaxy Laboratories Limited | Polymorph of 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid |
| CN101716132B (en) * | 2008-10-09 | 2012-01-11 | 北京方策方程医药科技有限公司 | Febuxostat enteric preparation |
| WO2012007487A1 (en) * | 2010-07-13 | 2012-01-19 | Interquim, S.A. | Process for preparing the crystalline form ii of febuxostat |
| CN102070558B (en) * | 2009-11-23 | 2012-08-22 | 欣凯医药化工中间体（上海）有限公司 | New crystal form of febuxostat and preparation method thereof |
| WO2013088449A1 (en) | 2011-12-16 | 2013-06-20 | Natco Pharma Limited | Stable crystal form of febuxostat and process for the preparation thereof |
| CN101780073B (en) * | 2009-01-21 | 2013-07-03 | 重庆圣华曦药业股份有限公司 | Febuxostat dispersible tablet drug and preparing method thereof |
| EP2619191A2 (en) | 2010-09-24 | 2013-07-31 | Hetero Research Foundation | Novel polymorphs of febuxostat |
| JP2013531020A (en) * | 2010-07-13 | 2013-08-01 | インテルキム、ソシエダッド アノニマ | Method for preparing crystalline form A of 2- [3-cyano-4- (2-i-butoxy) phenyl] -4-methyl-5-thiazole-carboxylic acid (febuxostat) |
| EP2692342A1 (en) | 2012-07-30 | 2014-02-05 | Interquim, S.A. | Process for the preparation of pharmaceutical compositions comprising febuxostat in the form of tablets |
| EP2718272A2 (en) | 2011-06-06 | 2014-04-16 | Hetero Research Foundation | Process for febuxostat |
| CN103936689A (en) * | 2009-07-17 | 2014-07-23 | 北京利乐生制药科技有限公司 | 2-[3-cyano-4-isobutoxy phenyl]-4-methylthiazole-5-formic acid crystal forms and preparation method thereof |
| CN104114545A (en) * | 2011-11-15 | 2014-10-22 | 迈兰实验室有限公司 | Process for the preparation of febuxostat polymorphs |
| EP3153158A1 (en) | 2015-10-09 | 2017-04-12 | Stada Arzneimittel Ag | Oral febuxostat tablet |
-
2007
- 2007-06-29 CN CNB2007100431784A patent/CN100546985C/en not_active Expired - Fee Related
Cited By (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101716132B (en) * | 2008-10-09 | 2012-01-11 | 北京方策方程医药科技有限公司 | Febuxostat enteric preparation |
| WO2010083752A1 (en) * | 2009-01-20 | 2010-07-29 | 重庆医药工业研究院有限责任公司 | High-purity febuxostat and the method for preparation |
| CN101780073B (en) * | 2009-01-21 | 2013-07-03 | 重庆圣华曦药业股份有限公司 | Febuxostat dispersible tablet drug and preparing method thereof |
| WO2010144685A1 (en) | 2009-06-10 | 2010-12-16 | Teva Pharmaceutical Industries Ltd. | Crystalline forms of febuxostat |
| US8742129B2 (en) | 2009-06-10 | 2014-06-03 | Teva Pharmaceutical Industries Ltd. | Crystalline forms of febuxostat |
| DE202010017868U1 (en) | 2009-06-10 | 2012-11-28 | Teva Pharmaceutical Industries Ltd. | Crystalline forms of febuxostat |
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| CN104114545B (en) * | 2011-11-15 | 2018-06-01 | 迈兰实验室有限公司 | It is used to prepare the method for Febuxostat polymorph |
| WO2013088449A1 (en) | 2011-12-16 | 2013-06-20 | Natco Pharma Limited | Stable crystal form of febuxostat and process for the preparation thereof |
| EP2692342A1 (en) | 2012-07-30 | 2014-02-05 | Interquim, S.A. | Process for the preparation of pharmaceutical compositions comprising febuxostat in the form of tablets |
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