CN105017372A - Crystal form of abiraterone acetate and preparation method of crystal form of abiraterone acetate - Google Patents
Crystal form of abiraterone acetate and preparation method of crystal form of abiraterone acetate Download PDFInfo
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- CN105017372A CN105017372A CN201510407599.5A CN201510407599A CN105017372A CN 105017372 A CN105017372 A CN 105017372A CN 201510407599 A CN201510407599 A CN 201510407599A CN 105017372 A CN105017372 A CN 105017372A
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- C07J—STEROIDS
- C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
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Abstract
The invention discloses a crystal form of abiraterone acetate. The crystal form is a beta crystal form. The abiraterone acetate in the crystal form has an X-ray powder diffraction spectrum basically shown the drawing 1 and a plurality of characteristic peaks from 0 degree to 50 degrees. The error of 2theta angle is +/-0.2, and the error of peak intensity is +/-20%. The grain size of the crystal form is 10+/-5 [mu]m, and the bioavailability can be effectively improved. The crystal form is suitable for various preparations and is simple in preparation method and high in stability.
Description
Technical field
The invention belongs to pharmaceutical chemistry technical field, be specifically related to a kind of Abiraterone acetate new crystal and preparation method thereof.
Background technology
Chemistry (3 β)-17-(3-pyridyl)-androstane-5, the 16-dien-3-ols acetic ester by name of Abiraterone acetate (Abiraterone Acetate, CAS:154229-18-2), structural formula is:
Abiraterone acetate is that a kind of CYP17 inhibitor is applicable to previously accept to shift castration refractory prostate cancer patient containing Docetaxel [docetaxel] chemotherapy for treating with prednisone coupling.For patients with prostate cancer, male hormones testosterone stimulates the growth of tumor of prostate.Medicine or operative treatment are used for reducing the generation of testosterone or stoping the effect of testosterone.
According to the document of open report, current Abiraterone acetate have many kinds, be specially: CN201010594577 reports alpha-crystal form, application for a patent for invention prospectus CN200910189173 reports A, B, C, D tetra-kinds of crystal formations, application for a patent for invention prospectus CN201110299046 reports crystal form E, and application for a patent for invention prospectus CN201110338041 reports I crystal.
Summary of the invention
The invention provides the beta crystal of Abiraterone acetate, the Abiraterone acetate of this crystal formation has X-ray powder diffraction as shown in Figure 1 substantially, the multiple characteristic peaks contained between 0 ~ 50 degree, the error at 2 θ angles is ± 0.2, and peak intensity error is ± 20%.
The invention provides a kind of crystal formation of Abiraterone acetate, this crystal formation is beta crystal, in the powder x-ray diffraction collection of illustrative plates represented with 2 θ angles, in following position indicating characteristic diffraction peak:
5.8530±0.2、9.5089±0.2、12.1012±0.2、12.6020±0.2、14.8543±0.2、15.1399±0.2、15.9772±0.2、17.2593±0.2、18.4451±0.2、18.9591±0.2、19.1396±0.2、19.8118±0.2、21.7172±0.2、21.9245±0.2、22.5008±0.2、23.1020±0.2、23.4220±0.2、24.3094±0.2、25.4126±0.2、26.0300±0.2、26.8396±0.2、27.5878±0.2、29.9095±0.2、34.5186±0.2、36.8344±0.2。
Wherein, peak intensity corresponding to each diffraction peak is followed successively by: 22.80%, 10.78%, 57.75%, 10.25%, 81.28%, 73.44%, 53.41%, 16.10%, 100.00%, 73.51%, 50.27%, 16.07%, 52.47%, 29.36%, 21.34%, 31.22%, 8.54%, 9.17%, 12.44%, 6.27%, 7.37%, 18.46%, 8.93%, 5.09%, 6.21%, and each peak intensity error is ± 20%.
Particularly, the powder x-ray diffraction figure of this crystal formation as shown in Figure 1.
Particularly, described crystal formation particle diameter is 5 ~ 15 μm.
The invention provides the method for the crystal formation of the above-mentioned Abiraterone acetate of preparation, comprise the steps:
1) Abiraterone acetate is dissolved in water-soluble organic solvent, obtains solution A;
2) get step 1) described in water-soluble organic solution mix with water, obtain solution B;
3) under agitation, solution A drops in solution B, controls solution B temperature and is less than 10 DEG C, after dropwising, mixed solution is cooled to-20 ~ 30 DEG C, stirring and crystallizing, filtration drying, obtains final product in dropping process.
Preferably, described water-soluble organic solvent is one of them or its combination of acetonitrile, methyl alcohol, Virahol, tetrahydrofuran (THF) or acetone.
Preferably, step 1) in, the mass volume ratio of Abiraterone acetate and water-soluble organic solvent is 1:5 ~ 40g/mL, preferred 1:8 ~ 15g/mL.
Preferably, step 2) in, the volume ratio of water and water-soluble organic solution is 5 ~ 20:1, preferably 8 ~ 15:1.
Preferably, step 3) described in mixed solution in the mass volume ratio of Abiraterone acetate and solvent be 1:8 ~ 40g/mL.
Preferably, step 3) in dropwise after mixed solution is cooled to-5 ~ 5 DEG C, stir 1 ~ 10h.
The crystal formation of Abiraterone acetate of the present invention is beta crystal, and this crystal formation particle diameter is 10 ± 5 μm, effectively can improve bioavailability, and this crystal formation is suitable for several formulations, and preparation method is simple, and stability is high.
Accompanying drawing explanation
Fig. 1 is the powder x-ray diffraction figure of the Abiraterone acetate beta crystal of embodiment 1;
Fig. 2 is the DSC collection of illustrative plates of the Abiraterone acetate beta crystal of embodiment 1.
Embodiment
Below in conjunction with the drawings and specific embodiments, the invention will be further described, can better understand the present invention and can be implemented, but illustrated embodiment is not as a limitation of the invention to make those skilled in the art.Specific embodiment is as follows:
Embodiment 1
1, the beta crystal preparation of the present embodiment Abiraterone acetate:
Taking Abiraterone acetate 10g is dissolved in 150mL acetone, slowly drops to (acetone: water=1:10, volume ratio) in 130mL aqueous acetone solution again, control temperature is less than 10 DEG C, stir 3 ~ 5h in 0 ± 5 DEG C after dropwising, filtration drying, obtains beta crystal crystal.
2, crystal formation checking: the beta crystal of Abiraterone acetate, the Abiraterone acetate of this crystal formation has X-ray powder diffraction as shown in Figure 1, specifically as shown in table 1:
Table 1
The beta crystal of the Abiraterone acetate of the present embodiment, the maximum endothermic transition that its DSC scans is at 151.91 DEG C, and Fig. 2 is shown in by the typical DSC collection of illustrative plates of Abiraterone acetate beta crystal.
3, yield, purity and effect:
As calculated, the yield of the present embodiment is 95.4%.
After measured, the beta crystal purity of Abiraterone acetate that the present embodiment prepares is 99.9%.
Particle diameter: after tested, the median size of the beta crystal crystal that the present embodiment obtains is 8 μm.
4, apply:
Through experimental verification: the beta crystal of Abiraterone acetate does the bioavailability that tablet improves tablet.
Embodiment 2
1, the beta crystal preparation of the present embodiment Abiraterone acetate:
Taking Abiraterone acetate 10g is dissolved in 140ml acetonitrile, slowly drops to (acetonitrile: water=1:8, volume ratio) in 150ml acetonitrile water again, control temperature is less than 10 DEG C, stir 3 ~ 5h in 0 ± 5 DEG C after dropwising, filtration drying, obtains beta crystal crystal.
2, crystal formation checking: through X-ray powder diffraction analysis, it is the beta crystal of Abiraterone acetate.
3, yield, purity and effect:
As calculated, the yield of the present embodiment is 95.1%.
After measured, the beta crystal purity of Abiraterone acetate that the present embodiment prepares is 99.8%.
Particle diameter: after tested, the median size of the beta crystal crystal that the present embodiment obtains is 12 μm.
4, apply:
Through experimental verification: the beta crystal of Abiraterone acetate does the bioavailability that tablet improves tablet.
Embodiment 3
1, the beta crystal preparation of the present embodiment Abiraterone acetate:
Taking Abiraterone acetate 10g is dissolved in 150ml tetrahydrofuran (THF), slowly drops to (tetrahydrofuran (THF): water=1:9, volume ratio) in 120ml tetrahydrofuran (THF) water again, control temperature is less than 10 DEG C, stir 3 ~ 5h in 0 ± 5 DEG C after dropwising, filtration drying, obtains beta crystal crystal.
2, crystal formation checking: through X-ray powder diffraction analysis, it is the beta crystal of Abiraterone acetate.
3, yield, purity and effect:
As calculated, the yield of the present embodiment is 94.7%.
After measured, the beta crystal purity of Abiraterone acetate that the present embodiment prepares is 99.7%.
Particle diameter: after tested, the median size of the beta crystal crystal that the present embodiment obtains is 9 μm.
4, apply:
Through experimental verification: the beta crystal of Abiraterone acetate does the bioavailability that tablet improves tablet.
Embodiment 4
1, the beta crystal preparation of the present embodiment Abiraterone acetate:
Taking Abiraterone acetate 10g is dissolved in 80ml acetone, slowly drops to (acetone: water=1:9, volume ratio) in 70ml aqueous acetone solution again, control temperature is less than 10 DEG C, stir 3 ~ 5h in 0 ± 5 DEG C after dropwising, filtration drying, obtains beta crystal crystal.
2, crystal formation checking: through X-ray powder diffraction analysis, it is the beta crystal of Abiraterone acetate.
3, yield, purity and effect:
As calculated, the yield of the present embodiment is 94.8%.
After measured, the beta crystal purity of Abiraterone acetate that the present embodiment prepares is 99.8%.
Particle diameter: after tested, the median size of the beta crystal crystal that the present embodiment obtains is 13 μm.
4, apply:
Through experimental verification: the beta crystal of Abiraterone acetate does the bioavailability that tablet improves tablet.
Embodiment 5
1, the beta crystal preparation of the present embodiment Abiraterone acetate:
Taking Abiraterone acetate 10g is dissolved in 100ml acetone, slowly drops to (acetone: water=1:15, volume ratio) in 160ml aqueous acetone solution again, control temperature is less than 10 DEG C, stir 3 ~ 5h in 0 ± 5 DEG C after dropwising, filtration drying, obtains beta crystal crystal.
2, crystal formation checking: through X-ray powder diffraction analysis, it is the beta crystal of Abiraterone acetate.
3, yield, purity and effect:
As calculated, the yield of the present embodiment is 95.0%.
After measured, the beta crystal purity of Abiraterone acetate that the present embodiment prepares is 99.8%.
Particle diameter: after tested, the median size of the beta crystal crystal that the present embodiment obtains is 7 μm.
4, apply:
Through experimental verification: the beta crystal of Abiraterone acetate does the bioavailability that tablet improves tablet.
The above embodiment is only that protection scope of the present invention is not limited thereto in order to absolutely prove the preferred embodiment that the present invention lifts.The equivalent alternative or conversion that those skilled in the art do on basis of the present invention, all within protection scope of the present invention.Protection scope of the present invention is as the criterion with claims.
Claims (10)
1. a crystal formation for Abiraterone acetate, is characterized in that, this crystal formation in the powder x-ray diffraction collection of illustrative plates represented with 2 θ angles, in following position indicating characteristic diffraction peak:
5.8530±0.2、9.5089±0.2、12.1012±0.2、12.6020±0.2、14.8543±0.2、15.1399±0.2、15.9772±0.2、17.2593±0.2、18.4451±0.2、18.9591±0.2、19.1396±0.2、19.8118±0.2、21.7172±0.2、21.9245±0.2、22.5008±0.2、23.1020±0.2、23.4220±0.2、24.3094±0.2、25.4126±0.2、26.0300±0.2、26.8396±0.2、27.5878±0.2、29.9095±0.2、34.5186±0.2、36.8344±0.2。
2. the crystal formation of Abiraterone acetate according to claim 1, it is characterized in that, peak intensity corresponding to each diffraction peak is followed successively by: 22.80%, 10.78%, 57.75%, 10.25%, 81.28%, 73.44%, 53.41%, 16.10%, 100.00%, 73.51%, 50.27%, 16.07%, 52.47%, 29.36%, 21.34%, 31.22%, 8.54%, 9.17%, 12.44%, 6.27%, 7.37%, 18.46%, 8.93%, 5.09%, 6.21%, and each peak intensity error is ± 20%.
3. the crystal formation of Abiraterone acetate according to claim 1, is characterized in that, the powder x-ray diffraction figure of this crystal formation as shown in Figure 1.
4. the crystal formation of Abiraterone acetate according to claim 1, is characterized in that, described crystal formation particle diameter is 5 ~ 15 μm.
5. prepare the method for the crystal formation of the Abiraterone acetate described in any one of Claims 1 to 4, it is characterized in that, comprise the steps:
1) Abiraterone acetate is dissolved in water-soluble organic solvent, obtains solution A;
2) get step 1) described in water-soluble organic solution mix with water, obtain solution B;
3) under agitation, solution A drops in solution B, controls solution B temperature and is less than 10 DEG C, after dropwising, mixed solution is cooled to-20 ~ 30 DEG C, stirring and crystallizing, filtration drying, obtains final product in dropping process.
6. method according to claim 5, is characterized in that, described water-soluble organic solvent is one of them or its combination of acetonitrile, methyl alcohol, Virahol, tetrahydrofuran (THF) or acetone.
7. method according to claim 5, is characterized in that, step 1) in, the mass volume ratio of Abiraterone acetate and water-soluble organic solvent is 1:5 ~ 40g/mL.
8. method according to claim 5, is characterized in that, step 2) in, the volume ratio of water and water-soluble organic solution is 5 ~ 20:1.
9. method according to claim 5, is characterized in that, step 3) described in mixed solution in the mass volume ratio of Abiraterone acetate and solvent be 1:8 ~ 40g/mL.
10. method according to claim 5, is characterized in that, step 3) in dropwise after mixed solution is cooled to-5 ~ 5 DEG C, stir 1 ~ 10h.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111303234A (en) * | 2020-02-28 | 2020-06-19 | 江西青峰药业有限公司 | Abiraterone acetate monocrystal and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101768199A (en) * | 2009-12-24 | 2010-07-07 | 深圳万乐药业有限公司 | Polymorphs of abiraterone acetate and preparation method thereof |
| CN102321142A (en) * | 2011-09-29 | 2012-01-18 | 重庆医药工业研究院有限责任公司 | Abiraterone acetate crystal form and preparation method thereof |
| CN102336801A (en) * | 2011-10-31 | 2012-02-01 | 南京卡文迪许生物工程技术有限公司 | Abiraterone acetate polymorphic substance and pharmaceutical composition |
| CN102558275A (en) * | 2010-12-20 | 2012-07-11 | 天津药物研究院 | Alpha type polycrystalline abiraterone acetate crystal, and preparation method, application and pharmaceutical composition thereof |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101768199A (en) * | 2009-12-24 | 2010-07-07 | 深圳万乐药业有限公司 | Polymorphs of abiraterone acetate and preparation method thereof |
| CN102558275A (en) * | 2010-12-20 | 2012-07-11 | 天津药物研究院 | Alpha type polycrystalline abiraterone acetate crystal, and preparation method, application and pharmaceutical composition thereof |
| CN102321142A (en) * | 2011-09-29 | 2012-01-18 | 重庆医药工业研究院有限责任公司 | Abiraterone acetate crystal form and preparation method thereof |
| CN102336801A (en) * | 2011-10-31 | 2012-02-01 | 南京卡文迪许生物工程技术有限公司 | Abiraterone acetate polymorphic substance and pharmaceutical composition |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111303234A (en) * | 2020-02-28 | 2020-06-19 | 江西青峰药业有限公司 | Abiraterone acetate monocrystal and preparation method thereof |
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