Polymorphism of mefloquine hydrochloride

Abstract

The polymorphic and pseudopolymorphic forms of mefloquine hydrochloride have been characterized by use of X-ray powder diffractometry, thermal analysis, infrared spectral analysis, scanning electron microscopy, and solubility measurements. It was determined that mefloquine hydrochloride can crystallize in at least eight forms, anhydrous forms (A, B′, E and M), solvate forms (B and I) and hydrate forms (C and D). The acetone solvate (form B) and isopropanol solvate (form I) transform into forms B ' and M, respectively, when they are heated on a hot stage. Form E, which was recrystallized from ethanol, showed gradual weight loss on heating, and a small endotherm in the DSC thennogram due to desolvation. However, the X-ray powder diffraction pattern of form E after removal of virtually all the ethanol, showed almost the same pattern. This suggests that ethanol is contained in channels within the crystal lattice of form E. An X-ray powder diffraction study showed that the crystal forms of mefloquine hydrochloride in lots of commercial tablets obtained from two sources were forms E and C. When the tablets were stored at 60°C, 75% R.H., form E was transformed into form D, but form C did not undergo a significant change. A study of the effect of various excipients on the solid-state crystal transformation revealed that microcrystalline cellulose promotes the transformation from form E into form D. However, methylcellulose, hydroxyethylcellulose, β-cyclodextrin, crospovidone and hydrous lactose have no effect on the crystal transformation.