Preparation and Characterization of a Novel Preparation of Itraconazole Nanoparticles with Improved Dissolution and Bioavailability

Abstract

The aim of the present work is to utilize the nanotechnology for preparing stable nanoparticles that enhance the dissolution and hence the bioavailability of poorly water-soluble Itraconazole (ITZ).  ITZ nanosuspensions were produced by nanoprecipitation method in the presence of surfactant (tween 80) and selected stabilizers (HPMC, PVP K 17 and Pluronic F 68) at different ratios with the drug. The nanosuspensions were evaluated for their physicochemical properties and drug content.  The nanoparticles were prepared by lyophilization technique and characterized by morphology evaluation, Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The optimized formulation showed an average particles size of 213.56 ± 19.58 nm and Zeta potential of -18.35 ± 2.55 mV.  In vitro cumulative release from the nanosuspension was 85.64% at 60 min when compared to pure drug 35.52% and freeze dried nanoparticles 93.81%. Pharmacokinetic studies revealed that AUC_(0–36) was increased by two folds when ITZ nanoparticles were administered orally compared with the market formulation (Sporanox^®), which in turn increased the bioavailability. Thus, Nanoparticles seems to be a promising approach for increasing the dissolution and enhancement the bioavailability of ITZ.