Spray dried inhalable ivacaftor co-amorphous microparticle formulations with leucine achieved enhanced in vitro dissolution and superior aerosol performance

Abstract

The present study aimed to develop inhalable powder formulations with both dissolution enhancement and superior aerodynamic properties for potential pulmonary delivery of a poorly water-soluble drug, ivacaftor (IVA). The IVA-leucine (LEU) microparticle formulations were produced by spray drying and the physicochemical, aerosolization and cytotoxicity properties were characterized. Co-amorphous microparticle formulation was formed at the IVA: LEU 3:1 M ratio with hydrogen bond interactions as indicated by Fourier transform infrared spectroscopy (FTIR) results. Dissolution rate of the co-spray dried formulations was significantly improved as compared with the IVA alone or physical mixtures. The co-spray dried formulations exhibited > 80% fine particle fraction (FPF) and > 95% emitted dose percentage (ED) values respectively, with superior physical and aerosolization stability under 40℃ at 75% RH for 30 days. The laser scanning confocal microscopy results demonstrated that more IVA was uptake by Calu-3 cell lines for the co-spray dried formulation. In summary, our results demonstrated that co-spray drying IVA with LEU could achieve enhanced in vitro release and superior aerodynamic properties for pulmonary delivery of IVA.