Study of heterogeneous equilibria in saturated aqueous solutions of some 7-chloro-1,4-benzodiazepines

Abstract

Acid-base equilibria in heterogeneous and homogeneous systems of some sparingly soluble benzodiazepines (diazepam, prazepam, chlordiazepoxide and medazepam) were investigated in aqueous solution and the corresponding equilibrium constants were determined by the application of pH-metric, spectrophotometric and solubility methods. The sites of protonation were predicted on the basis of the analysis of the corresponding carbon-13 nuclear magnetic resonance spectra. In addition, buffer characteristics of saturated aqueous solutions of these drugs in the presence of the solid phase were investigated and it was established that they possess a very high buffer capacity over a specific pH range.