Long-Chained Fatty Acid-Based Solid Dispersions of Voriconazole as an Effective Strategy For Achieving Sustained...

Voriconazole (VCZ), a second-generation triazole antifungal agent, possesses high oral bioavailability but is associated with substantial pharmacokinetic variability influenced by food intake and physiological conditions. This study aimed to develop sustained-release solid dispersions (SDs) of VCZ using long-chain fatty acids-stearic acid (SA), palmitic acid (PA), and myristic acid (MA)-to modulate drug dissolution and improve pharmacokinetic consistency. SDs were prepared using the melt-fusion method at drug-to-fatty acid ratios of 0.5:1 and 1:1 (w/w) and were systematically characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), hot-stage polarized microscopy (HSM), Fourier-transform infrared spectroscopy (FTIR), intrinsic dissolution rate (IDR), and in vitro diffusion studies. The 1:1 (w/w) SDs exhibited markedly slower and sustained drug release compared to pure VCZ and physical mixtures under both acidic (0.1 N HCl) and stepwise dissolution study. PXRD confirmed that VCZ retained its crystalline nature within the formed SD. DSC and HSM indicated complete solubilization of VCZ in the molten carrier without recrystallization. FTIR studies revealed hydrogen bonding between VCZ and the fatty acids. Among the tested formulations, SD (VCZ:MA) provided the most favorable combination of sustained release and enhanced permeability, as evidenced by in vitro diffusion studies. Furthermore, minimum inhibitory concentration (MIC) testing confirmed that all SD formulations maintained antifungal activity. Overall, the findings highlight long-chain fatty acid-based SDs as a promising strategy for achieving sustained VCZ release and reducing pharmacokinetic variability, warranting further in vivo evaluation.