title: Tris(hydroxymethyl) aminomethane salt of ramipril: synthesis, structural characterization from X-ray powder diffraction and stability studies.
abstract: 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 P2(1) with a=24.3341(15), b=6.4645(5), c=9.5357(7) Å, β=96.917(3)° and V=1489.1(3) Å(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 (110) 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 °C is only 1.5%. The solution phase analysis at different pH values also reveals a greater stability of ramipril-tris (II) over ramipril (I).
authors.affiliation: Department of Physics, Jadavpur University, Jadavpur, Kolkata 700032, India.
authors.forename: Abir
authors.initials: A
authors.lastname: Bhattacharya
authors.forename: Basab
authors.initials: B
authors.lastname: Chattopadhyay
authors.forename: Santu
authors.initials: S
authors.lastname: Chakraborty
authors.forename: Bhairab N
authors.initials: BN
authors.lastname: Roy
authors.forename: Girij P
authors.initials: GP
authors.lastname: Singh
authors.forename: Himangshu M
authors.initials: HM
authors.lastname: Godbole
authors.forename: Umesh B
authors.initials: UB
authors.lastname: Rananaware
authors.forename: Alok K
authors.initials: AK
authors.lastname: Mukherjee
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003460:Crystallization; D018360:Crystallography, X-Ray; D004355:Drug Stability; D006358:Hot Temperature; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D015394:Molecular Structure; D033362:Powder Diffraction; D017257:Ramipril / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods*; D013997:Time Factors; D014325:Tromethamine / Q000031:analogs & derivatives / Q000138:chemical synthesis*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D014325:Tromethamine; D017257:Ramipril