Optimizing voriconazole-loaded thermoresponsive hydrogel: in silico tools and ex vivo studies.

Objective: The present study aims to develop and evaluate the voriconazole-loaded thermoresponsive hydrogel using in silico tools.

Methods: Poloxamer 407 and PEG 400 were selected as the components from in silico studies for thermoresponsive hydrogel of voriconazole. The cohesive energy density (CED) and solubility parameters (SP) were calculated using Biovia Material Studio 2022 software to predict the polymer-polymer miscibility and drug-polymer miscibility. Different evaluation techniques used to select the optimized formulation. The in vitro antimicrobial activity against Candida albicans was determined for the optimized formulation to illustrate the efficacy of the developed formulation.

Results: Hydrogel containing 15% poloxamer exhibited gelation time of 92.67 ± 3.51 s, and gelation temperature of 36.67 °C with good spreadability of 13.00 ± 0.02 cm². CED values for poloxamer 407, PEG 400, and Voriconazole individually were found to be 3.23 × 10^-8, 3.21 × 10^-8, 4.84 × 10^-8, respectively, whereas in the combination of poloxamer 407 and PEG 400 was found to 3.85 × 10^-8 and in ratio 9:1 was found to be 3.81 × 10^-8 indicated the best miscibility between poloxamer 407 and PEG 400 in 9:1 ratio. Based on solvation-free energy of voriconazole (-48.343 kJ/mol) ethanol was selected as the solvent system. Optimized formulation showed the sustained release over the 36 h and good antimicrobial effect.

Conclusion: A thermoresponsive hydrogel of voriconazole was developed using Biovia Material Studio 2022, integrating computational predictions and molecular dynamics simulations to streamline polymer and solvent selection. This approach minimized trial-and-error experiments, enabling efficient formulation while enhancing understanding of polymer-polymer and drug-polymer interactions.