Solid-state characterization of tacrine hydrochloride

none6noThe present study deals with the physicochemical characterization of solid forms of tacrine monohydrochloride (TCR), a centrally active reversible acetylcholinesterase inhibitor for treating the symptoms of mild to moderate Alzheimer's disease, obtained by recrystallization of hot saturated solutions from different solvents. Recrystallization of the commercially available hydrate, TCR center dot H2O, from water, hydroalcoholic solutions with ethanol, n-propanol, methanol and isopropanol (1:1, v/v) and isopropanol/water (8:2, v/v) afforded a new dihydrate phase TCR center dot 2H(2)O form I. The TCR samples obtained by desolvation of TCR center dot H2O and TCR center dot 2H(2)O show temperature and melting enthalpy values very similar, thus confirming the existence of a unique anhydrous crystalline phase. Exposure of anhydrous TCR powder samples under different atmospheric conditions at room temperature, resulted in rehydration to TCR center dot H2O at 32% relative humidity (RH), whereas at 100% RH a new solid form of TCR center dot 2H(2)O (TCR center dot 2H(2)O form II), i.e. a polymorph of the dihydrate isolated by recrystallization, was obtained. Differential scanning calorimetry (DSC), simultaneous thermogravimetric analysis (TGA/DSC), and thermo optical analysis (TOA) with support from X-ray powder diffractometry (PXRD) and Fourier transform infrared spectroscopy (FT-IR), were used for the characterization of the isolated solid forms of TCR and monitoring the water uptake of anhydrous TCR. (C) 2011 Elsevier B.V. All rights reserved.noneSorrenti M.; Catenacci L.; Bruni G.; Luppi B.; Bigucci F.; Bettinetti G.Sorrenti M.; Catenacci L.; Bruni G.; Luppi B.; Bigucci F.; Bettinetti G