Fabrication of Ketoconazole Nanoformulation Using Extra Virgin Olive Oil: A Comparative Pharmacokinetic and Stability Study

Abstract

Ketoconazole belongs to the class II drugs of the biopharmaceutical classification system and has low solubility issues. In the market, the available drug ketoconazole is 200-400 mg and is associated with low solubility. To cope with these issues nanoemulsion is formulated. During the fabrication of the nanoemulsion, olive oil was used as a lipid, tween 80 as a surfactant, and PEG 600 as a co-surfactant. By changing these ratios of surfactants and co-surfactants, formulations with different particle sizes and polydispersity index were obtained. The optimized lipid-based nanoparticles obtained have a particle size of 50.29 nm, polydispersity index of 0.377, and Zeta potential -17.2 mv. They have an entrapment efficiency of 78% and a drug loading capacity of 3.97%. Further characterization through the FTIR study showed that there is no interaction between drug excipients. The scanning electron microscopy showed white patches, which also confirmed nanoparticles formation. The XRD analysis showed that the drug changed from crystalline to amorphous form. The in vitro study was conducted, and the nanoformulation showed better bioavailability than the marketed one. A statistical model was applied to the in vitro study. The stability study was conducted at different temperatures, and the formulation was found stable at refrigerated, room, and hot temperatures. The in vivo antifungal study proved that nanoformulation has a better recovery rate as compared to the marketed one. The similarity index was 69.3, and the peaks of nanoformulation were above the marketed one in terms of release kinetics. It is concluded from the study that nanoformulation was better in terms of recovery, release, and cost than the marketed drug.