Solid-state characterization of tacrine hydrochloride.
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.
Department of Drug Sciences, University of Pavia, V.le Taramelli, 12, 27100 Pavia, Italy. milena.sorrenti@unipv.it
Milena
M
Sorrenti
Laura
L
Catenacci
Giovanna
G
Bruni
Barbara
B
Luppi
Federica
F
Bigucci
Giampiero
G
Bettinetti
D000433:1-Propanol / Q000737:chemistry; D019840:2-Propanol / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D003460:Crystallization; D018360:Crystallography, X-Ray; D000431:Ethanol / Q000737:chemistry; D006813:Humidity; D000432:Methanol / Q000737:chemistry; D018697:Nootropic Agents / Q000737:chemistry*; D033362:Powder Diffraction; D011208:Powders; D012997:Solvents / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013619:Tacrine / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods; D013818:Thermogravimetry; D044366:Transition Temperature; D014867:Water / Q000737:chemistry
D002800:Cholinesterase Inhibitors; D018697:Nootropic Agents; D011208:Powders; D012997:Solvents; D014867:Water; D000431:Ethanol; D013619:Tacrine; D000433:1-Propanol; D019840:2-Propanol; D000432:Methanol