Polymorphism of rac-5,6-diisobutyryloxy-2-methylamino-1,2,3,4-tetrahydro-naphthalene hydrochloride (CHF 1035). I. Thermal, spectroscopic, and X-ray diffraction properties

The polymorphism of rac-5,6-diisobutyryloxy-2-methylamino-1,2,3,4-tetrahydr o-naphthalene hydrochloride (CHF 1035) was investigated. Three different cr ystal forms (Form I, Form II, and Form III) were obtained by recrystallizat ion procedures from common organic solvents. The polymorphs were characteri zed by Raman and carbon-13 nuclear magnetic resonance (C-13 NMR) spectrosco py, in solution and in solid state (cross polarization-magic angle spinning ), powder X-ray diffractometry, and thermal methods (differential scanning calorimetry, hot stage microscopy, and thermogravimetry). Moreover, the dif fraction patterns of Form I, collected at controlled temperatures, gave evi dence of the presence of two reversible structural rearrangements at simila r to 60 and similar to 75 degreesC. These structural variations were confir med by the results obtained by differential scanning calorimetry and hot st age microscopy techniques. The analysis of the Raman spectra allowed the id entification of peculiar absorption bands for each polymorph. Form III was the stable crystal form at room temperature as determined by the basis of s lurry conversion method. (C) 2001 Wiley-Liss, Inc. and the American Pharmac eutical Association.