Enzymatic process for obtaining 17α-monoesters of cortexolone and/or its 9,11-dehydroderivatives
The present invention refers to a new enzymatic process for obtaining 17α-monoesters of cortexolone and/or its 9,11-dehydroderivatives starting from the corresponding 17α,21-diesters which comprises an enzymatic alcoholysis reaction. Furthermore, the present invention refers to new crystalline forms of cortexolone 17α-propionate and 9,11-dehydro-cortexolone 17α-butanoate.
1. Crystalline form IV of cortexolone-17α-propionate characterized by a DRX as shown in FIG. 28 .
2. Crystalline form IV of cortexolone-17α-propionate characterized by XRPD peaks at about 4.8, 12.9, 14.4, 15.8, 16, 19.3, and 19.5 degrees 2theta.
3. A process for preparing crystalline form IV of cortexolone-17α-propionate, the process comprising crystallizing cortexolone-17α-propionate from a propylene glycol/water or polyethylene glycol/water mixture.
4. The process of claim 3 , wherein the propylene glycol/water mixture has a ratio of propylene glycol to water of from about 1/2 to about 2/1.
5. The process of claim 4 , wherein the ratio of propylene glycol to water is about 1/1.
6. The process of claim 3 , wherein the polyethylene glycol/water mixture has a ratio of polyethylene glycol to water of from about 1/2 to about 2/1.
7. The process of claim 6 , wherein the ratio of polyethylene glycol to water is about 1/1.
8. The process of claim 3 , wherein the propylene glycol/water mixture has a ratio of propylene glycol to water of from about 1/3 to about 3/1.
9. Crystalline form IV of cortexolone-17α-propionate prepared by the process of claim 3 .
10. Crystalline form IV of cortexolone-17α-propionate prepared by the process of claim 4 .
11. Crystalline form IV of cortexolone-17α-propionate prepared by the process of claim 5 .
12. Crystalline form IV of cortexolone-17α-propionate prepared by the process of claim 6 .
13. Crystalline form IV of cortexolone-17α-propionate prepared by the process of claim 7 .
14. A pharmaceutical composition comprising crystalline form IV of cortexolone-17α-propionate, water, and at least one physiologically acceptable excipient.
15. The composition of claim 14 , wherein the at least one physiologically acceptable excipient is propylene glycol, cetylic alcohol, glyceryl monostearate, liquid paraffin, or a combination of any of the foregoing.
16. The composition of claim 14 , further comprising mixed tocopherols, polysorbate 80, or a combination thereof.
17. The composition of claim 14 , wherein the composition is in the form of a cream.
18. The composition of claim 14 , wherein the composition further comprises solubilized cortexolone-17α-propionate.
19. The composition of claim 18 , wherein the solubilized cortexolone-17α-propionate and crystalline form IV of cortexolone-17α-propionate together comprise 0.1 to 2% by weight of the composition.
20. The composition of claim 19 , wherein the solubilized cortexolone-17α-propionate and crystalline form IV of cortexolone-17α-propionate together comprise 0.2 to 1% by weight of the composition.
21. The composition of claim 14 , wherein the crystalline form IV of cortexolone-17α-propionate is present at from about 0.1 to about 2% by weight of the composition.
22. A pharmaceutical composition comprising crystalline form IV of cortexolone-17α-propionate.
23. The composition of claim 22 , wherein the composition is in the form of a tablet, capsule, powder, pellet, suspension, emulsion, cream, gel, ointment, lotion, or paste.
24. The composition of claim 22 , wherein the composition is in the form of a solid, semi-solid, or a paste.