Solid state characterization of mometasone furoate anhydrous and monohydrate forms

Abstract

Mometasone furoate is a potent glucocorticoid anti-inflammatory agent. Its anhydrous Form 1 and monohydrate form were characterized by X-ray crystallography, X-ray powder diffraction at ambient and elevated temperature, thermal analysis, FT-IR, and dynamic moisture adsorption. In Form 1, mometasone furoate molecules pack tightly with molecules interlocked in a space group of P2(1)2(1)2(1). The monohydrate form crystallizes in space group P1. The unit cell of the monohydrate contains one water molecule and one mometasone furoate molecule. The water molecules form channels along the a axis and mometasone furoate molecules pack in layers in the same direction. Dehydration was observed between 60 and 100 degrees C by thermogravimetric analysis with a heating rate of 10 degrees C/min. It corresponds to a broad endotherm over the same temperature range in the differential scanning calorimetry with the same heating rate. Variable temperature X-ray powder diffraction reveals that a new anhydrous form (Form 2) was fully produced above 90 degrees C. This crystalline form was converted to Form 1 after being heated above 150 degrees C; and was totally converted to the monohydrate after 1 day at 23 degrees C, 45% RH.