Crystallinity, hygroscopicity and dissolution of moricizine hydrochloride hemihydrate.

A typical anhydrous moricizine hydrochloride, an antiarrhythmic agent, is a non-hygroscopic crystalline material. Three lots of moricizine hydrochloride were found to deliquesce within a day at 85% relative humidity, exhibit different X-ray powder diffraction (XRPD) patterns and have more rapid dissolution rate than that of typical anhydrous material. No change in XRPD pattern was observed when the solvent (ethanol) was removed from these lots by heating to 80 degrees C. A two-step water release was observed by thermogravimetric analysis (TGA): a surface water release and a water of hydration release, for these heated samples. The stoichiometry of the water of hydration suggests that it is a hemihydrate. The dissolution rate of the hemihydrate was faster than that of typical anhydrous material. This hemihydrate could be converted to a typical anhydrous material by heating to 90 degrees C. The granules obtained by a simulated wet granulation process on typical lots and typical lots containing up to 20% of hemihydrate exhibited similar physical behaviour to that of typical anhydrous material.