In-Vitro and In-Vivo Pharmacokinetic Study of Solid Lipid Nanoparticles Containing Poorly Soluble Antifungal Drug

https://doi.org/10.5281/zenodo.18972082

Abstract

The poor water solubility of many antifungal drugs limits their therapeutic effectiveness. Ketoconazole, a broad-spectrum antifungal agent, suffers from low oral bioavailability due to its limited solubility and extensive first-pass metabolism. This study aimed to develop solid lipid nanoparticles (SLNs) to enhance the solubility, stability, and pharmacokinetic profile of ketoconazole. SLNs were prepared using the hot homogenization technique with stearic acid as the lipid base and poloxamer 188 as the surfactant. The optimized nanoparticles had an average size of 142 ± 5 nm, a zeta potential of −29 mV, and an encapsulation efficiency of 89%. Fourier-transform infrared spectroscopy showed no chemical interactions between the drug and excipients. Differential scanning calorimetry and X-ray diffraction analyses suggested the drug was partially amorphized within the lipid matrix. In vitro release studies demonstrated an initial rapid release followed by sustained drug release over 72 hours, indicating controlled diffusion from the lipid core. Pharmacokinetic evaluation in Wistar rats revealed a 3.1-fold increase in oral bioavailability and prolonged mean residence time compared to standard drug suspensions. Additionally, antifungal activity against Candida albicans was improved, as shown by larger inhibition zones. These findings indicate that SLNs are a promising nanocarrier system to improve delivery and bioavailability of poorly soluble antifungal drugs.