Engineered inhalable micro-balloon shaped drug particles for carrier-free dry powder inhalation (DPI) application

Abstract

The study presents inhalable balloon-like hollow spherical salbutamol sulfate micro-particles (SS μb ) as potential carrier-free alternative to drug-excipient formulation for dry powder inhalation. SS μb is engineered from commercial salbutamol sulfate (SS, active pharmaceutical ingredient) through ultrasound-assisted crystallization coupled with stirring technique. The optimized processing conditions allowed tailored particle properties such as shape and size critical for high drug dose requirements. Time-resolved particle growth study reveals that the hollow structure is formed by mass diffusion of SS from the interior to exterior surface of the droplet generated during process. The analytical investigations of SS μb display 87.19% crystallinity with same chemical identity as SS and better flowability. The in-vitro aerosolization for SS μb shows 37.4% fine particle fraction and 95.1% emitted dose compared to 5.9% and 75.9% respectively for SS as carrier-free formulation. This is attributed to the hollow, porous, spherical particles with low surface charges and comparatively large particle size, surface roughness. • Balloon-like hollow spherical salbutamol sulfate (SS μb ) micro-particles. • Particles engineered through sonocrystallization coupled with mixing technique. • SS μb are crystalline, flowable and exhibit same molecular properties as SS. • Achieved high emitted dose (95%) in in-vitro aerosolization studies. • Suitable for high drug dose (37.4% FPF) through carrier-free DPI route.