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 now crystalline forms of cortexolone-17α-propionate and 9,11-dehydro-cortexolone 17α-butanoate.
1 . A pharmaceutical composition comprising cortexolone 17α-propionate in at least one of polymorphic forms I, III, or IV, propylene glycol, cetyl alcohol, glyceryl monostearate, liquid paraffin, tocopherol, polyoxyethylene (20) sorbitan monooleate, and water.
2 . The pharmaceutical composition of claim 1 , wherein the cortexolone 17α-propionate comprises solvate crystalline form IV of cortexolone 17α-propionate.
3 . The pharmaceutical composition of claim 1 , wherein the cortexolone 17α-propionate comprises cortexolone 17α-propionate of crystalline form III.
4 . The pharmaceutical composition of claim 2 , wherein the cortexolone 17α-propionate further comprises cortexolone 17α-propionate of crystalline form III.
5 . The pharmaceutical composition of claim 1 , wherein the cortexolone 17α-propionate is present in the composition in an amount of 0.1 to 2 wt %.
6 . The pharmaceutical composition of claim 2 , wherein the cortexolone 17α-propionate is present in the composition in an amount of 0.1 to 2 wt %.
7 . The pharmaceutical composition of claim 1 , wherein the cortexolone 17α-propionate is present in the composition in an amount of 0.2 to 1 wt %.
8 . The pharmaceutical composition of claim 2 , wherein the cortexolone 17α-propionate is present in the composition in an amount of 0.2 to 1 wt %.
9 . The pharmaceutical composition of claim 1 , wherein the cortexolone 17α-propionate is present in the composition in an amount of about 1 wt %.
10 . The pharmaceutical composition of claim 2 , wherein the cortexolone 17α-propionate is present in the composition in an amount of about 1 wt %.
11 . The pharmaceutical composition of claim 1 , wherein the tocopherol is mixed tocopherols.
12 . The pharmaceutical composition of claim 1 , wherein the composition is formulated for topical administration.
13 . The pharmaceutical composition of claim 2 , wherein the composition is formulated for topical administration.
14 . The pharmaceutical composition of claim 1 , wherein the composition is an emulsion.
15 . The pharmaceutical composition of claim 2 , wherein the composition is an emulsion.
16 . The pharmaceutical composition of claim 1 , wherein the composition is a cream.
17 . The pharmaceutical composition of claim 2 , wherein the composition is a cream.
18 . The pharmaceutical composition of claim 14 , wherein the composition is a cream.
19 . The pharmaceutical composition of claim 1 , wherein the composition comprises:
about 1 wt % cortexolone 17α-propionate,
about 24.7 wt % propylene glycol,
about 2.5 wt % cetyl alcohol,
about 14.8 wt % glyceryl monostearate,
about 9.9 wt % liquid paraffin,
about 1 wt % polyoxyethylene (20) sorbitan monooleate.
20 . The pharmaceutical composition of claim 19 further comprising about 0.05 wt % tocopherol.
21 . A method of treating acne in a subject in need thereof, the method comprising topically administering an effective amount of the pharmaceutical composition of claim 1 to an affected area on the subject.