文摘
Tris(hydroxymethyl) aminomethane (tris) salt of API ramipril was synthesized, and characterized by FTIR, TG-DSC and ab initio X-ray powder structure analysis. The compound, ramipril-tris (II), crystallizes in the monoclinic space group P21 with a = 24.3341(15), b = 6.4645(5), c = 9.5357(7) ?, ¦Â = 96.917(3)¡ã and V = 1489.1(3) ?3. The crystal structure has been determined from laboratory X-ray powder diffraction data using direct space global optimization strategy (simulated annealing) followed by the Rietveld refinement. A network of intermolecular OH¡O, CH¡N and CH¡O hydrogen bonds between the ramipril-ramipril, tris-tris and ramipril-tris components in the compound generates a two-dimensional molecular assembly in (1 1 0) plane. A comparative study of solid-state stabilities of ramipril-tris (II) with that of ramipril (I) and ramipril-erbumine (III) indicates that ramipril-tris (II) is the most stable one among the three, and the conversion to impurity D after 72 h at 80 ¡ãC is only 1.5 % . The solution phase analysis at different pH values also reveals a greater stability of ramipril-tris (II) over ramipril (I).