• Sumit Arora, Mehra Haghi, Paul M Young, Michael Kappl, Daniela Traini, and Sanyog Jain.
• a Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics , National Institute of Pharmaceutical Education and Research (NIPER) , Mohali , India.
• Expert Opin Drug Deliv. 2016 Jan 1; 13 (2): 183-93.

ObjectiveTo develop and characterize a highly respirable dry powder inhalable formulation of voriconazole (VRZ).MethodsPowders were prepared by spray drying aqueous/alcohol solutions. Formulations were characterized in terms of particle size, morphology, thermal, moisture responses and aerosolization performance. Optimized powder was deposited onto an air-interface Calu-3 model to assess their uptake across Calu-3 lung epithelia. Optimized formulation was evaluated for stability (drug content and aerosol performance) for 3 months. Additionally, Calu-3 cell viability, lung bioavailability and tissue distribution of optimized formulation were evaluated.ResultsParticle size and aerosol performance of dry powder containing 80% w/w VRZ and 20% w/w leucine was appropriate for inhalation therapy. Optimized formulation showed irregular morphology, crystalline nature, low moisture sensitivity and was stable for 3 months at room temperature. Leucine did not alter the transport kinetics of VRZ, as evaluated by air-interface Calu-3 model. Formulation was non-cytotoxic to pulmonary epithelial cells. Moreover, lung bioavailability and tissue distribution studies in murine model clearly showed that VRZ dry powder inhalable formulation has potential to enhance therapeutic efficacy at the pulmonary infection site whilst minimizing systemic exposure and related toxicity.ConclusionThis study supports the potential of inhaled dry powder VRZ for the treatment of fungal infections.

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