Ketoconazole-loaded microspone film coating agent for superficial fungal infection: design, preparation and characterization

Ketoconazole (KCZ), an imidazole antifungal drug, is constrained by its low solubility and poor stability, restricting its effective absorption and bioavailability. This study introduces a KCZ-loaded microsponge based film coating agent (KCZ-MSF), designed to enhance the transdermal absorption and bioavailability of KCZ. The KCZ-MS was prepared by emulsion solvent evaporation method and the composition of the prescription was optimized by Box-Behnken design (BBD). Moreover, characterization of the optimized KCZ-MS was conducted using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The film coating agent's preparation was further optimized through orthogonal experiments, converting the optimized KCZ-MS into a film coating agent suitable for topical skin application. The KCZ-MS showed a spherical porous structure with a mean particle size of 22.42 ± 8.45 μm, a drug loading efficiency of 20.74%, entrapment efficiency of 92.12%, and good compatibility between the drug and excipients. The optimized KCZ-MSF displayed good physical properties. In vitro transdermal experiments revealed that the skin retention of KCZ-MSF surpassed that of commercially available KCZ cream at 6, 12, and 24 h. The pharmacokinetic experiment results indicate that the area under the curve ( AUC 0-24 ) of KCZ-MSF 420.71 ± 21.77 μg/(g·h) is 2.05 times that of KCZ film coating agent (KCZ-F) and 1.29 times that of commercially available ketoconazole cream. Therefore, KCZ-MSF presents a more promising platform for the treatment of superficial skin fungal infections.