A new spherically agglomerated drug composite system with lactose for dry powder inhalation

In order to prepare a dry powder inhalation (DPI) formulation for steroids, we designed crystal agglomerates consisting of fine drug crystals suitable for DPI that disintegrated into primary crystals in the inhalation device at emission. Using these agglomerates, we developed a new spherically agglomerated drug composite system with lactose for DPI of steroids with a Jethaler®. The drug agglomerates were prepared by the method of spherical agglomeration in liquid with control of the particle size of the primary drug crystal, agglomerates and mechanical strength of agglomerates by changing the agitation speed of the agglomeration system before (5°C-1000 r.p.m.) and after (5°C-300 r.p.m.) the dispersing medium was saturated with bridging liquid. The agglomerates in the DPI formulation disintegrated into respirable primary crystals by collision with coformulated lactose particles in the milling chamber of the device when inhaled. The DPI formulation with these agglomerates exhibited a higher fine particle (= respirable) fraction (FPF: 24.5%) than the formulation with fine drug particles (FPF: 16.1%) as evaluated in vitro with a cascade impactor. The inhalation property of the present DPI formulationwas determined by the particle size of coformulated lactose particles. It was found that 325M lactose (approximately 60 μm mean diameter) was most suitable to improve the inhalation properties of the present system.