Preparation and characterization of salt forms of enalapril

Abstract

Selection of an optimal salt form of a drug candidate is a vital component of preformulation stage of drug development. In this study, six salts of enalapril - citrate, mesylate, tartrate, malate, besylate and tosylate - were prepared and characterized by Mass Spectroscopy, Differential Scanning Calorimetry, Thermogravimetric Analysis, Microscopy, Powder X-ray Diffraction, Karl Fischer Titration, High Performance Liquid Chromatography, Fourier-Transform Infra-red Spectroscopy and Head Space Gas Chromatography. All the six salts were subjected to a tiered screening involving five stages in the following order: crystallinity, hygroscopicity, solubility, stability and flow/compactability. Enalapril malate showed encouraging profile because of its lower hygroscopicity, higher solubility, good solid state stability, and better flow and compactability, in comparison to the marketed maleate salt. Copyright © Informa UK, Ltd.