Formulation and characterization of Itraconazole as Nanosuspension dosage form for enhancement of solubility

Abstract EN

Itraconazole (ITZ) is a triazole antifungal agent given orally for the treatment of oropharyngeal and vulvovaginal candidiasis, for systemic infections including aspergillosis, candidiasis, and for the prophylaxis of fungal infections in immunocompromised patients.

The objective of the study was to formulate a nanosuspension for a practically water-insoluble ITZ to increase aqueous solubility and improve its dissolution and oral bioavailability.

ITZ nanosuspension was produced by a solvent-antisolvent nanoprecipitation method in the presence of different stabilizers (Poloxamer-188 and HPMCE5) at different ratios with the drug alone or combination with surfactants (tween 80 and SLS).The results exhibit that the particle size values of all prepared itraconazole formulations were in the nano size range.

The best formula (F6) has a particle size of 42 nm and zeta potential of - 21.86 mV.

In vitro cumulative release percent from the nanosuspension was 88 % at 30 min and from lyophilized nanoparticles was 98.2% when compared to the pure drug 13.5%.

Additionally, the effects of different parameters on the prepared formulas were investigated.Several characterization methods were done for the optimized nanoparticles prepared by lyophilization technique, such as FTIR, DSC, XRD and SEM, which showed smooth uniform particles within the nano size.

FTIR shows no change in the position of the ITZ nanosuspension functional group; XRD and DSC show no significant change in the crystallinity of lyophilized nanoparticles.Thus, nanosuspension appears to be a promising approach to increase the water solubility and the dissolution rate of ITZ.