Amphiphilic drug promethazine hydrochloride-additive systems: evaluation of thermodynamic parameters at cloud point

Abstract

At the cloud point (CP, where phase separation occurs), the thermodynamic properties of aqueous buffer solution of the amphiphilic phenothiazine drug promethazine hydrochloride (PMT) are calculated in the presence of various additives (viz., alcohols, surfactants, and polymers). PMT undergoes clouding phenomena, which depend upon the physicochemical conditions (e.g., concentration, pH, temperature, etc.). As the clouding components release their solvated water, they separate out from the solution. Therefore, the CP of an amphiphile can be considered the limit of its solubility. Herein, we report the thermodynamics of clouding in PMT in the presence of additives. The standard Gibbs energy change of solubilization (Δ_sG⁰) for all of the additives is found to be positive. However, the standard enthalpy change (Δ_sH⁰) and the product of temperature and the standard entropy change (TΔ_sS⁰) values are negative as well as positive depending upon the type and nature of the additive. The results are discussed on the basis of these factors.