Crystalline Forms of 3-Beta-Amino 17-Methylene Androstane-6-Alpha 7-Beta-Diol Hydrochloride

Abstract

The invention relates to novel crystalline forms of 3-beta-amino-17-methylene-androstane-6-alpha,7-beta-diol hydrochloride, referred to as form A, form B and form C, a method for preparing same, the use thereof as a drug, and pharmaceutical compositions containing same.

Description

EXAMPLE 1

3-beta-amino-17-methylene-androstane-6-alpha,7-beta-diol hydrochloride, Form A.

250 mg of compound of formula I is dissolved at ambient temperature in minimum amount of methanol. Isopropylic ether is added until the onset of precipitation. After filtration, 195 mg of form A of is obtained.

EXAMPLE 2

3-beta-amino-17-methylene-androstane-6-alpha,7-beta-diol hydrochloride, Form A.

250 mg of compound of formula I is dissolved at ambient temperature in minimum amount of ethanol. Water is added until the onset of crystallization; polymorph B of is obtained.

Then after evaporation under a stream of nitrogen at ambient temperature, form A is obtained.

EXAMPLE 3

3-beta-amino-17-methylene-androstane-6-alpha,7-beta-diol hydrochloride, Form B.,

Left for 3 days under a relative humidity above 95% form A of converts to form B

EXAMPLE 4

3-beta-amino-17-methylene-androstane-6-alpha,7-beta-diol hydrochloride, Form C.,

250 mg of compound of formula I is dissolved at ambient temperature in minimum amount of methyl ethyl ketone (MEK). After transfer in water by azeotropic distillation at constant volume and equilibration under a relative humidity above 97%, form C of compound of formula lis obtained.

Claims

1) Crystalline form A of 3-beta-amino-17-methylene-androstane-6-alpha,7-beta-diol hydrochloride corresponding to the structure:

2) Crystalline form A of 3-beta-amino-17-methylene-androstane-6-alpha,7-beta-diol hydrochloride characterized by the fact that the unit cell is monoclinic (space group P2, Z=2) and the unit cell parameters at T=295 K are:

3) Di-hydrated crystalline form B of 3-beta-amino-17-methylene-androstane-6-alpha,7-beta-diol hydrochloride, characterized by the fact that the indexing of the lines of the powder X-ray diffraction pattern diagram at 295 K is:

4) Di-hydrated crystalline form B of 3-beta-amino-17-methylene-androstane-6-alpha,7-beta-diol hydrochloride, characterized by the fact that the unit cell is triclinic (space group P1, Z=1) and the unit cell parameters at T=295 are:

5) Monohydrate crystalline form C of 3-beta-amino-17-methylene-androstane-6-alpha,7-beta-diol hydrochloride, characterized by the fact that the indexing of the first 30 lines of the powder X-ray diffraction pattern diagrams at 295 K is

6) Monohydrate crystalline form C of 3-beta-amino-17-methylene-androstane-6-alpha,7-beta-diol hydrochloride, characterized by the fact that the unit cell is triclinic (space group P1, Z=1) and the unit cell parameters T=295 K are:

7) A process for the preparation of form A as defined in claims 1 or 2, characterized by the fact that crystallization takes place in a mixture of alcohol and ether and particularly in an isopropylic methanol-ether mixture.

8) A process for the preparation of form C as defined in claim 5 or 6, characterized by the fact that 250 mg of compound of formula (1) are dissolved at ambient temperature in a solvent such as methyl ethyl ketone (MEK); and then transferred in water by azeotropic distillation at constant volume and equilibration at a relative humidity above 97%.

9) As medications, crystalline forms A, B or C as defined by claims 1 to 6.

10) A pharmaceutical composition characterized by the fact that it comprises form A of 3-beta-amino-17-methylene-androstane-6-alpha,7-beta-diol hydrochloride in a pure state or possibly in combination with either one of/or both crystalline forms B or C and/or in combination with any compatible and pharmaceutically acceptable excipient or inert diluent.

11) A method of treating inflammatory diseases, wherein the method comprises administering a pharmaceutical composition comprising one or more cystalline forms A, B or C as defined by claims 1 to 6 to a human.