Dry powder inhalation of Itraconazole-loaded nanotransferosome: formulation and aerodynamic characteristics

Abstract

Background- Itraconazole is a broad-spectrum synthetic triazole antifungal agent that can be used for the treatment of pulmonary aspergillosis in the form of Dry powder inhaler (DPI). DPIs are a type of pulmonary drug delivery devices that can deliver drugs locally for action in the lungs for the treatment of respiratory diseases or even for the systemic drug delivery. Transferosome is introduced as a novel biocompatible vesicular system which has potential for administration in pulmonary drug delivery. Aim- The present study was designed to prepare Itraconazole-loaded transferosomes and then fabrication of its DPI formulation by spray drying technique. Methods- Itraconazole-loaded nanotransferosomes with three different types of surfactant in varying concentrations were prepared by the conventional film hydration method followed by probe sonication technique. Size and size distribution of nanotramsferosomes were evaluated by laser light scattering method. The optimized nanotransferosomes were turned into dry powder form by co-spray drying with varying amounts of mannitol. The aerosolization efficiency and aerodynamic properties of dry powders were determined by next generation impactor (NGI). The amount of Itraconazole in the stages of NGI was measured by our developed HPLC technique. Results- The optimized Nanotransferosome composed of Lecithin and Span60 in the ratio of 90:10 was prepared in the size of 171 nm (volume mean diameter) with narrow size distribution pattern. Drug loading increased the size to around 518nm. Different types of surfactants did not influence the size significantly. Discussion: Scanning electron microscopy images confirmed the formation of aggregated nanoparticles in the suitable range for pulmonary drug delivery. Aerosolization evaluation of co-spray dried formulations with different amounts of mannitol indicated that 2:1 ratio of mannitol:transferosome (w:w) showed the best aerosolization efficiency (fine particle fraction (FPF)=37%). Increasing of mannitol significantly decreased the FPF of the optimized formulations.