Development and characterization of nintedanib inhalable powders as a potential pulmonary fibrosis treatment

Abstract

Nintedanib is an orally administered intracellular tyrosine kinase inhibitor approved for idiopathic pulmonary fibrosis. Differently from oral treatment, dry powder inhalers (DPIs) can deliver a higher drug concentration at the target site, reducing doses and systemic side effects. The aim of this work was to develop dry powders of Nintedanib with properties suitable for inhalation therapy. Particles were prepared by spray drying the drug alone (3–5% w/v) or with appropriate excipients, from different hydroalcoholic solutions i.e., water/ethanol (7/3 v/v) or water/isopropyl alcohol (from 7/3 v/v to 5/5 v/v) mixtures. The powders obtained were characterized in terms of process yield, particle size distribution, morphology, density and aerodynamic properties. The results indicated that leucine improved the aerosol performance of the powders, increasing the value of the fine particle fraction (FPF) from 47.9 % in the drug only batches to 73.1 % using 5 % w/w leucine. This improvement was attributed to the ability of the amino acid to change both the surface area of the particles and the fluidity of the powder. Therefore, this study demonstrated the possibility of developing dry powder of Nintedanib for local administration in the lungs for the treatment of pulmonary fibrosis.