Solid-state characterization of tacrine hydrochloride

• Published in: Journal of pharmaceutical and biomedical analysis 2012-04, Vol.63, p.53-61
• Main Authors: Sorrenti, Milena, Catenacci, Laura, Bruni, Giovanna, Luppi, Barbara, Bigucci, Federica, Bettinetti, Giampiero
• Format: Article
• Language: English
• Subjects: 1-propanol; 1-Propanol - chemistry; 2-Propanol - chemistry; acetylcholinesterase; Alzheimer disease; Analysis; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Cholinesterase Inhibitors - chemistry; Crystallization; Crystallography, X-Ray; Differential scanning calorimetry; enthalpy; ethanol; Ethanol - chemistry; Fourier transform infrared spectroscopy; Fundamental and applied biological sciences. Psychology; General pharmacology; Humidity; isopropyl alcohol; Medical sciences; melting point; methanol; Methanol - chemistry; monitoring; Nootropic Agents - chemistry; Pharmacology. Drug treatments; Powder Diffraction; Powders; rehydration; relative humidity; Simultaneous thermogravimetric analysis; solvents; Solvents - chemistry; Spectroscopy, Fourier Transform Infrared; Tacrine - chemistry; Tacrine monohydrochloride; Technology, Pharmaceutical - methods; temperature; Thermogravimetry; Transition Temperature; water; Water - chemistry; water uptake; X ray powder diffractometry; X-radiation
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2011.12.023

► In this work we characterize solid forms of tacrine monohydrochloride (TCR). ► A new hydrate phase TCR·2H2O form I was obtained by recrystallization. ► A polymorphic form TCR·2H2O form II was isolated. The 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·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·2H2O form I. The TCR samples obtained by desolvation of TCR·H2O and TCR·2H2O 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·H2O at 32% relative humidity (RH), whereas at 100% RH a new solid form of TCR·2H2O (TCR·2H2O 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.