Enzymatic process for obtaining 17 alpha-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. A topical composition comprising crystalline cortexolone-17α-propionate in at least two crystalline forms selected from the group consisting of crystalline Form I, crystalline Form II, crystalline Form III, and crystalline Form IV, wherein
crystalline Form I is characterized by a DRX with at least peaks at about: 7.6, 8.4, 17.0, and 20.1 degrees 2theta,
crystalline Form II is characterized by a DRX with at least peaks at about: 10.8, 13.3, 16.5, and 21.9 degrees 2theta,
crystalline Form III is characterized by a DRX with at least peaks at about: 6.2, 12.6, 22.4, and 23.7 degrees 2theta, and
crystalline Form IV has a DRX with at least peaks at about: 4.8, 12.9, and 19.5 degrees 2theta.
2. The topical composition of claim 1 , wherein the composition comprises crystalline Form I and any of crystalline Forms II, III, or IV, or any combination thereof.
3. The topical composition of claim 1 , wherein the composition comprises crystalline Form II and any of crystalline Forms I, III, or IV, or any combination thereof.
4. The topical composition of claim 1 , wherein the composition comprises crystalline Form III and any of crystalline Forms I, II, or IV, or any combination thereof.
5. The topical composition of claim 1 , wherein the composition comprises crystalline Form IV and any of crystalline Forms I, II, or III, or any combination thereof.
6. The topical composition of claim 1 , wherein cortexolone-17α-propionate is present in the formulation in a total amount ranging from 0.1 to 2% by weight.
7. The topical composition of claim 5 , wherein the composition comprises crystalline Forms III and IV.
8. The topical composition of claim 5 , wherein the composition comprises crystalline Form I, II, and IV.
9. The topical composition of claim 5 , wherein the composition comprises crystalline Forms I, III, and IV.
10. The topical composition of claim 5 , wherein the composition comprises crystalline Forms I and IV.
11. The topical composition of claim 5 , wherein the composition comprises crystalline Forms II, III, and IV.
12. The topical composition of claim 5 , wherein the composition comprises crystalline Forms II and IV.