Tris(hydroxymethyl) aminomethane salt of ramipril: Synthesis, structural characterization from X-ray powder diffraction and stability studies

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• 作者：Abir Bhattacharya ; Basab Chattopadhyay ; Santu Chakraborty ; Bhairab N. Roy ; Girij P. Singh ; Himangshu M. Godbole ; Umesh B. Rananaware ; Alok K. Mukherjee
• 关键词：Ramipril salt ; X-ray powder diffraction ; Crystal structure ; Stability study ; Thermal analysis
• 刊名：Journal of Pharmaceutical and Biomedical Analysis
• 出版年：2012
• 出版时间：November, 2012
• 年：2012
• 卷：70
• 期：Complete
• 页码：280-287
• 全文大小：716 K

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).