Crystallization induced flower-like lactose as potential carriers for dry powder inhaler application

The study documents the flower-like lactose particles as potential carriers to improve Dry Powder Inhaler (DPI) efficiency. The lactose particles (LM<inf>x</inf>, LM<inf>f</inf>) are prepared by anti-solvent crystallization and compared with commercial lactose carriers (Inhalac 251; LM<inf>c</inf>). Formulations of 1.48% w/w drug loading are prepared using salbutamol sulfate (model drug) and different lactose carriers. The carrier properties are correlated with %FPF using principal component analysis. The analytical results confirm LM<inf>x</inf> is α-lactose monohydrate, LM<inf>f</inf> comprises α and β-lactose. Time-resolved crystal growth shows that the LM<inf>x</inf> particle is agglomerated structure while, LM<inf>f</inf> particle appear as flower-like structure of size (~45.37–63.92 μm) with high surface and aerodynamic properties compared to LM<inf>c</inf>. The in-vitro aerosolization studies resulted in higher fine particle fraction (%FPF) for formulations with LM<inf>x</inf> (~33.23%) and LM<inf>f</inf> (~44.85%) compared to LM<inf>c</inf> (~23.40%). The high %FPF is mainly attributed to the higher surface roughness, amorphicity, surface energy of engineered lactose carriers.