title: Stabilization of quinapril by incorporating hydrogen bonding interactions.
abstract: In the present study stability of various known solvates of quinapril hydrochloride has been compared with nitromethane solvate. Nitromethane solvate was found to be more stable compared to other known solvates. Single crystal X-ray diffraction analysis of quinapril nitromethane solvate shows intermolecular hydrogen bonding between quinapril molecule and nitromethane. Stabilization of quinapril by forming strong hydrogen bonding network as in case of co-crystals was further studied by forming co-crystal with tris(hydroxymethyl)amino methane. Quinapril free base forms a stable salt with tris(hydroxymethyl)amino methane not reported earlier. Quinapril tris(hydroxymethyl)amino methane salt found to be stable even at 80 degrees for 72 h i.e. hardly any formation of diketopiperazine and diacid impurity. As expected single crystal X-ray diffraction analysis reveals tris(hydroxymethyl)amino methane salt of quinapril shows complex hydrogen bonding network between the two entities along with ionic bond. The properties of this stable salt - stable in solid as well as solution phase, might lead to an alternate highly stable formulation.
authors.affiliation: Lupin Ltd. (Research Park), 46A, 47A - Nande Village, Mulshi Taluka, Pune-411 042, India.
authors.forename: B N
authors.initials: BN
authors.lastname: Roy
authors.forename: G P
authors.initials: GP
authors.lastname: Singh
authors.forename: H M
authors.initials: HM
authors.lastname: Godbole
authors.forename: S P
authors.initials: SP
authors.lastname: Nehate