Physicochemical Properties and Solubility of Hydrochloride Mucolytic Agents

Abstract

Two widely used active pharmaceutical ingredients (API), ambroxol hydrochloride (AMB·HCl) and bromhexine hydrochloride (BMH·HCl), belong to the expectorant and mucokinetic group of drugs. Their applications are found in the treatment of the upper respiratory tract and bronchopulmonary diseases. The compounds have similar chemical structures, but are different enough to distinguish their physicochemical properties. To understand better the bioavailability of the drugs a series of experiments was performed to establish significant parameters. With differential scanning calorimetry (DSC) the temperature and the enthalpy of fusion were determined with no observed polymorphic transformations. The phase diagrams for binary systems {active agent (1) + solvent (2)} were determined with three solvents: 1-octanol, water and ethanol, to describe phase equilibria by correlation with the local composition models: Wilson, UNIQUAC and NRTL. Finally, the Bates–Schwarzenbach method was used to establish the ionization constants of AMB·HCl and BMH·HCl at two temperatures: room temperature 298.2 K and human body temperature 310.2 K. Our study can give an insight into further drug delivery system design and help to create more effective drug application forms.