Design and evaluation of itraconazole loaded solid lipid nanoparticulate system for improving the antifungal therapy

ABSTRACT

The objective of the study was to design and evaluate Itraconazole loaded solid lipid nanoparticles [SLNs] drug delivery system, where Itraconazole nanoparticles with suitable size ranges are expected to improve the therapeutic efficacy and reduction of toxicity of this broad spectrum antifungal agent. Components of the SLNs were lipid [palmitic acid] and surfactants [Pluronic F127 and Tween 40]. The Itraconazole loaded nanoparticles were prepared by microemulsion dispersion method. Experiments were carried out with optimized ratio of excipients, where drug-lipid ratio and surfactant-cosurfactant ratio [Km] were varied to optimize the formulation characteristics. The effects of dispersion media, its pH, ionic content, etc. were investigated to optimize the SLNs production. Particles size analysis and zeta potential measurements were done using Malvern Mastersizer Hydro 2000G. The particles were also subjected to DSC, IR and XRD analyses. The in vitro drug release profile from nanoparticles was found to prolong up to 12h. Kinetic analysis of release indicated that nanoparticles formed were matrix in nature, in which Itraconazole dispersed uniformly. Optimized formulations were found to have a lipid-drug ratio of 1.51 and prepared at a Km ratio of 12 to maximize drug loading, modulate release and minimized particle size. The microemulsion mediated nanoparticle preparation methodology ensured high drug loading [ca. 80%], low and narrow size distribution and provided a reproducible and fast production method. The study elaborates on the feasibility and suitability of lipid based colloidal drug delivery system, employing optimize design to develop a clinically useful nanoparticle system with targeting potential