Assessment of clouding behaviour and physico-chemical parameters of triton X-100 and metformin hydrochloride drug mixture: Understanding the impacts of hydrotropic compounds

Abstract

The study of the effect of various hydrotropes (HYTs) on the clouding behaviour of surfactant-drug mixture is imperative to enhance the pharmaceutical preparation. The hydrophobic nature of organic compounds demands a rigorous approach to boost the solubility of sparingly soluble drugs or organic molecules in aqueous solvents. Hydrotropes (HYTs) could be a unique selection to improve the liquid solubility of drugs that are not much soluble in water. In order to investigate the liquid solubility of surfactant and drug, the cloud point (CP) or lower consolute temperature (LCT) detection technique was used to examine the clouding phenomenon of Triton X-100 (TX-100) and metformin hydrochloride (MMH) mixed system in aqueous solutions of HYTs (o-cresol, caffeine, nicotinamide, urea, and glycerol). The CP values of TX-100 + MMH drug mixture are increased in the presence of caffeine, nicotinamide, and urea whereas the CP values decreased in presence of o-cresol and glycerol. In the current investigation, the values of Gibbs free energy (${\Delta G}_c^0$) were observed positive, so the clouding process was of TX-100 + MNH mixture nonspontaneous. But, when the HYT concentration rose, these values progressively experienced a drop. In aqueous HYTs media, the entropy change (${\Delta S}_c^0$) was positive (except o-cresol, and glycerol), as well as the enthalpy change (${\Delta H}_c^0$) was also found positive (except o-cresol, and glycerol). The ${\Delta H}_c^0$ and ${\Delta S}_c^0$ results indicate that intermolecular interactions, such as hydrogen bonding, dispersion forces, Debye forces, dipole-dipole interactions, as well as hydrophobic interactions, are the main forces between TX-100 + MMH in the presence of HYTs. The molar heat capacity $\left({\Delta C}_c^0\right)$, compensation temperature (T_c), and intrinsic enthalpy gain (${\Delta H}_c^{0,\ast }$) were also computed and logically interpreted. Comprehending the surfactant-drug interaction is essential for developing efficient drug formulations and enhancing the surfactant-drug system for broad-ranges of industrial applications.