Optimization and Evaluation of Ketoconazole Loaded Nanostructured Lipid Carriers Employing Microwave-Assisted Technique

Abstract

The present research work is designed to formulate, optimize and evaluate the ketoconazole loaded nanostructured lipid carriers for the topical delivery. Ketoconazole loaded nanostructured lipid carriers were prepared by one pot single-step microwave assisted technique using Compritol® 888 ATO, Labrafac PG and soya lecithin employing 2-factors 3-level experimental design. The p-size of the optimized batch of microwave assisted ketoconazole loaded nanostructured lipid carriers was found to be 60.15 nm. The in vitro drug release in 24 h study showed the biphasic release pattern, initial burst release for 5 h followed by slower release upto 24 h. Furthermore, ex vivo skin permeation study revealed that 3670.99 μg/cm2 and 4644.78 μg/cm2 of drug permeated from ketoconazole loaded nanostructured lipid carriers hydrogel and marketed formulation with the flux rate of 305.91 μg/cm2/h and 387.06 μg/cm2/h, respectively at the end of 24 h. Confocal laser scanning microscope images demonstrated appreciable cell uptake of 5(6)-Carboxyfluorescein loaded nanostructured lipid carriers hydrogel compared to 5(6)-Carboxyfluorescein-loaded plain hydrogel. Optimized batch of nanostructured lipid carrier formulation produced by microwave assisted technique produced particles in nm range with narrow polydispersity index and high entrapment efficiency. X-ray study confirmed that the crystalline nature of ketoconazole changed to amorphous form in the process of nanostructured lipid carrier formulation and thermal behavior analyzed by differential scanning calorimetry confirmed inclusion of drug into lipid matrix in its amorphous form. After performing the optimization and evaluations of nanostructured lipid carriers it can be concluded that nanostructured lipid carriers bear the potential to be explored further for the topical and other pharmaceutical applications.