Investigations on the polymorphism and pseudopolymorphism of clobetasone butyrate

Abstract

Clobetasone butyrate was investigated for polymorphism and pseudopolymorphism. Solvent mediated conversion experiments reveal that the commercially available form I represent the thermodynamically most stable form at room temperature and DSC measurements shows that it should also be the most stable form until melting. Form I crystallizes in space group P2 1 2 1 2 1 with three crystallographically independent molecules of similar conformation. From methanol an additional pseudo polymorphic form was discovered. In the crystal structure (space group P2 1 2 1 2 1 ) the solvent molecules are connected to the clobetasone butyrate molecules by O-H···O hydrogen bonding. Investigations of the solvate using thermogravimetry, differential thermoanalysis as well as differential scanning calorimetry proves, that on solvent removal an amorphous form is obtained that crystallizes into form I on further heating.