Crystalline anhydrate forms of a pharmaceutical

Abstract

The invention provides and describes solid state 17α-ethynyl-androst-5-ene-3β,7β,17β-triol including amorphous and crystalline forms and specific polymorphic forms thereof. Anhydrates and solvates of 17α-ethynyl-androst-5-ene-3β,7β,17β-triol include Form I anhydrate and Form IV and Form V solvates. The invention further relates to solid and suspension formulations containing 17α-ethynyl-androst-5-ene-3β,7β,17β-triol in a described solid state form and use of the formulations to treat hyperglycemic conditions, such as type 2 diabetes and metabolic syndrome, and autoimmune conditions, such as rheumatoid arthritis, ulcerative colitis and type 1 diabetes, among other inflammation related conditions in subjects or human patients. The invention also relates to methods to make liquid formulations from solid state forms of 17α-ethynyl-androst-5-ene-3β,7β,17β-triol and uses of such formulations in treating the described conditions.

1 . Crystalline anhydrate 17α-ethynylandrost-5-ene-3β,7β,17β-triol. 
     
     
         2 . The crystalline anhydrate 17α-ethynylandrost-5-ene-3β,7β,17β-triol of  claim 1  substantially free of amorphous 17α-ethynylandrost-5-ene-3β,7β,17β-triol. 
     
     
         3 . A method to make a crystalline anhydrate 17α-ethynylandrost-5-ene-3β,7β,17β-triol of  claim 1  wherein the crystalline anhydrate is Form II 17α-ethynyl-androst-5-ene-3β,7β,17β-triol comprising the steps of
 a) slurrying crystalline anhydrate Form I 17α-ethynyl-androst-5-ene-3β,7β,17β-triol in ethyl acetate or methylethylketone; 
 b) separating the solid and liquid phases of the slurry obtained from step (a); and 
 c) evaporating the solvent from the liquid phase obtained from step (b), 
 whereby crystalline anhydrate Form II 17α-ethynyl-androst-5-ene-3β,7β,17β-triol is obtained. 
 
     
     
         4 . The method of  claim 3  wherein the compound of 17α-ethynyl-androst-5-ene-3β,7β,17β-triol in Form I is substantially pure or has a purity of 99% or greater. 
     
     
         5 . The method of  claim 3  wherein the crystalline anhydrate Form I 17α-ethynyl-androst-5-ene-3β,7β,17β-triol is micronized prior to the slurrying of step (a). 
     
     
         6 . The method of  claim 5  wherein the micronized crystalline anhydrate Form I 17α-ethynyl-androst-5-ene-3β,7β,17β-triol has a particle size defined by (Dv, 90) between about 5 micron and about 30 micron. 
     
     
         7 . The method of  claim 6  wherein the micronized crystalline anhydrate Form I 17α-ethynyl-androst-5-ene-3β,7β,17β-triol has a particle size defined by (Dv, 90) of about 7 micron. 
     
     
         8 . The method of  claim 3  wherein the slurrying of step (a) is preformed at ambient temperature for 9 days. 
     
     
         9 . The method of  claim 3  wherein the separation of step (b) is preformed by filtering the slurry obtained from step (a) through a 0.2 micron filter. 
     
     
         10 . The method of  claim 3  wherein the evaporation of step (c) is preformed under ambient temperature and pressure. 
     
     
         11 . A method to make a crystalline anhydrate 17α-ethynylandrost-5-ene-3β,7β,17β-triol of  claim 1  by desolvation of Form III or Form IV 17α-ethynylandrost-5-ene-3β,7β,17β-triol.