QbD Driven Solid Dispersion Development for Enhanced Solubility and Dissolution of BCS Class II Drug: Voriconazole as a Model Drug

Abstract

Voriconazole (VC), a second-generation triazole antifungal, suffers from low aqueous solubility (~0.5 mg/mL), which restricts its oral bioavailability. The present study sought to enhance the solubility and dissolution profile of VC through solid dispersion (SD) technology, employing PEG 4000 and PEG 6000 as hydrophilic carriers. A systematic Quality by Design (QbD) framework was applied to optimize the formulation. A Central Composite Design (CCD) was implemented to evaluate the influence of PEG concentrations on solubility (Y₁) and cumulative drug release (Y₂). Phase solubility studies confirmed the formation of VC-PEG complexes exhibiting AL-type profiles. Numerical optimization, supported by graphical analysis, identified the optimized formulation consisting of 600 mg of PEG 4000 and 600 mg of PEG 6000. The optimized solid dispersion demonstrated a marked improvement in solubility (30.68 mg/mL) and drug release (cumulative drug release = 89.88%), achieving a desirability score of 0.901, thereby validating the robustness of the QbD-based optimization strategy.Model validation confirmed excellent predictive performance (adjusted R² and predicted R² within acceptable limits). Solid-state characterization (FTIR, DSC, XRD, SEM) indicated complete amorphization and uniform molecular dispersion of VC. Stability studies over six months confirmed the stability of the formulation (f 2 = 78.27). PEG-based solid dispersions offer a promising and stable approach to improve the solubility and dissolution of poorly watersoluble antifungal agents such as voriconazole.