Novel polymorph form M of mifepristone and process for its preparation
Mifepristone substantially in polymorph form M is provided. Also provided is a process for the preparation of polymorph form M of mifepristone comprising the steps of (a) dissolving crude mifepristone in a polar solvent at an elevated temperature to obtain a clear solution; (b) cooling the solution to a temperature and for a time period sufficient to form a precipitate of mifepristone crystals; and (c) isolating the precipitate of mifepristone crystals to obtain the polymorph form M of mifepristone.
1 . Mifepristone substantially in polymorph form M.
2 . The mifepristone substantially in polymorph form M of claim 1 , further characterized by a X-ray diffraction pattern (XRD) substantially in accordance with FIG. 1 .
3 . The mifepristone substantially in polymorph form M of claim 1 , further characterized by characteristic peaks (expressed in degrees 2θ±0.2°θ) at approximately one or more of the positions: about 17.26 and about 18.50.
4 . The mifepristone substantially in polymorph form M of claim 1 , further characterized by having an Infrared (IR) spectrum substantially in accordance with FIG. 2 .
5 . The mifepristone substantially in polymorph form M of claim 1 , further characterized by a differential scanning calorimetry (DSC) thermogram substantially in accordance with FIG. 3 .
6 . Substantially pure polymorph form M of mifepristone.
7 . A process for the preparation of polymorph form M of mifepristone, the process comprising the steps of:
(a) dissolving crude mifepristone in a polar solvent at an elevated temperature to obtain a clear solution;
(b) cooling the solution to a temperature and for a time period sufficient to form a precipitate of mifepristone crystals; and
(c) isolating the precipitate of mifepristone crystals to obtain the polymorph form M of mifepristone.
8 . The process of claim 7 , wherein the polar solvent in step (a) comprises an alcohol.
9 . The process of claim 7 , wherein the polar solvent in step (a) comprises a C 1 -C 18 alcohol.
10 . The process of claim 7 , wherein the polar solvent in step (a) comprises an alcohol selected from the group consisting of methyl alcohol, ethyl alcohol, isopropyl alcohol, propyl alcohol and mixtures thereof.
11 . The process of claim 7 , wherein the amount of polar solvent in step (a) is about 2.5 to about 2.7 volume of the crude mifepristone.
12 . The process of claim 7 , wherein the temperature in step (a) is about 75 to about 80° C.
13 . The process of claim 7 , wherein the step of isolating comprises filtering the precipitate of mifepristone crystals.
14 . The process of claim 13 , wherein the step filtering is carried out with a filter aid.
15 . The process of claim 14 , wherein the filter aid is celite.
16 . The process of claim 7 , wherein the temperature of cooling the solution is about −5 to about −10° C.
17 . The process of claim 7 , further comprising drying the isolated polymorph form M of mifepristone.
18 . The process of claim 7 , further comprising drying the isolated polymorph form M of mifepristone at a temperature of about 50° C. to about 55° C.
19 . A pharmaceutical composition comprising the polymorph form M of mifepristone of claim 1 and one or more pharmaceutically acceptable excipients.
20 . A pharmaceutical composition comprising the polymorph form M of mifepristone of claim 3 and one or more pharmaceutically acceptable excipients.