Development of a binary lipid nanoparticles formulation of itraconazole for parenteral administration and controlled release

Abstract

The principal aim of this study was to develop an intravenous formulation of itraconazole (ITZ) using lipid nanoparticles based on binary mixture of liquid and solid lipids. Lipid nanoparticles were developed to provide the controlled release of ITZ as well as to improve the solubility of ITZ. Lipid nanoparticles were prepared with tristearin as a solid lipid, triolein as a liquid lipid, and a surfactant mixture of eggPC, Tween 80 and DSPE-PEG 2000. ITZ was incorporated at the concentration of 20 mg/g. Lipid nanoparticles were manufactured by high-pressure homogenization method. The particle size and polydispersity index (PI) of lipid nanoparticles were below 280 nm and 0.2, respectively. Zeta potentials and incorporation efficiencies of lipid nanoparticles were around −30 mV and above 80%, respectively. Lipid nanoparticles containing 1% of liquid lipid showed the smallest particles size and the highest incorporation efficiency. Results from SEM, DSC and PXRD revealed that ITZ in lipid nanoparticles exists in an amorphous state. Release rates were increased as the amount of liquid lipid in lipid core increased, demonstrating that the release of ITZ from lipid nanoparticles could be controlled by modulation of the amount of liquid lipid in lipid core. Pharmacokinetic studies were performed after intravenous administration of lipid nanoparticles in rats at the dose of 5 mg/kg. The plasma concentration of ITZ was prolonged after intravenous administration of lipid nanoparticles. It is concluded that binary lipid nanoparticles could control the release and pharmacokinetic parameters of ITZ.