Impacts of Short-Chain Alcohols on the Cloudy Development and Thermodynamics of Triton X-100 and Metformin Hydrochloride Drug Mixture

Cloud point (CP) of aqueous solution of metformin hydrochloride (MNH) and triton X-100 (TX-100) was examined in presence of several alcohols (MeOH, EtOH, 1-PrOH, 2-PrOH, and 1-BuOH). The main focal point of this study was to evaluate the cloud development for the combination of TX-100 and MNH, as well as to indicate the mode of how various alcohols influence both the physicochemical parameters and interaction forces of that mixture. The cloud point (CP) measurement technique was chosen because of its broad applicability in both the medical and industrial sectors. As alcohol contents increased, higher CP values of TX-100 and MNH mixture were observed except in aq. 1-BuOH (CP is decreased). In the aqueous alcoholic medium (above 3000 mmol·kg⁻¹), the phase separation of TX-100 (92.7 mmol·kg⁻¹) and MNH (2 mmol·kg⁻¹) mixture showed the subsequent trend: CP (H₂O + 2-PrOH) ˃ CP (H₂O + MeOH) > CP (H₂O + EtOH) ˃ CP (H₂O + 1-PrOH). It was observed that the depth to which alcohol molecules penetrate micelles is influenced by the length of the alcohol chain. Longer hydrophobic alcohol molecules have the ability to impair more ethylene oxide–water (EO-water) interactions by penetrating deeper into the micelle’s palisade layer. As a result, there is more occurrence of dehydration, which promotes the production of micellar particles as well as lowers the cloud point substantially. The calculated \({\Delta G}_{c}^{0}\) values of the TX-100 + MNH mixture in alcohols media are appeared as positive in every scenario examined, proving that the clouding procedure is not spontaneous. The positive \({\Delta G}_{c}^{0}\) results might be attributed to the surfactant’s surface layer in forming H-bond via the water molecules. A decrease in the positive \({\Delta G}_{c}^{0}\) values is evidenced by a rise in alcohol concentrations. Consequently, there is less non-spontaneity at higher alcohol concentrations. The \(+{\Delta H}_{c}^{0}\) (endothermic) and \(+{\Delta S}_{c}^{0}\) magnitudes are detected in aq. MeOH, EtOH, and 2-PrOH solutions. However, \({\Delta H}_{c}^{0}\) and \({\Delta S}_{c}^{0}\) magnitudes are found as positive (endothermic) and negative (exothermic) at lower and higher contents of 1-PrOH solution while the opposite trend in the \({\Delta H}_{c}^{0}\) and \({\Delta S}_{c}^{0}\) was detected in aq. 1-BuOH solution.

Graphical Abstract

Possible interactions among TX-100 and metformin hydrochloride in aqueous 1-BuOH media