Hydrotrope dynamics: unraveling solubility pattern and correlation of benzimidazole using response surface methodology expert system

Solubilizing drugs in liquid and semisolid environments typically involves the use of cosolvents or surfactants. In contrast, the utilization of hydrotropic agents, which are small hydrophilic organic compounds like sodium salicylate or sodium benzoate, has been less explored in the field of pharmaceutical formulations. However, particularly in the context of topical dosage forms, hydrotropic solubilization can present valuable alternatives for enhancing solubility. One challenge in employing hydrotropic solubilization has been the unpredictability of its effectiveness with different drug molecules. In the current study, three different hydrotropes namely sodium salicylate, sodium benzoate, and pyrogallol were chosen to test the solubility enhancement of benzimidazole drug. Optimization of solubility was proceeded with Central Composite Design obtained from RSM expert system. It was noticed from the results that sodium salicylate had performed the best compared to the other two chosen hydrotropes. This was also reexamined using two models namely modified Apelblat model and polynomial model. The thermodynamic studies were assessed and it had reconfirmed the acquired solubility study results. The minimum and maximum hydrotrope concentrations of sodium salicylate required were 0.4 and 2.25 mol/L, respectively. The solubility enhancement factor was also remarkably high for sodium salicylate with 36.91 ± 0.07. With careful selection of the appropriate hydrotropic agent, the solubility of poorly soluble drug, benzimidazole has been significantly improved.