Formulation of inhalable beclomethasone dipropionate-mannitol composite particles through low-temperature supercritical assisted atomization

Abstract

Mannitol carrier and drug-carrier composite particles were produced via low-temperature supercritical assisted atomization (LTSAA). The enhanced aerosolization of the mannitol carrier particles with added L-leucine could be attributed to the formation of fine corrugated particles, which reduced the interparticle cohesion and led to better flowability of the mannitol carrier particles. A poorly water-soluble drug, beclomethasone dipropionate (BDP), and mannitol co-precipitated during LTSAA with the optimal addition of 9.1 mass % L-leucine. The in vitro aerosolization and dissolution experiments indicated that the fine particles fraction (FPF) of the drug-carrier composite particles was 3.4 times (FPF = 49.9 %) higher than that of the as-received BDP (FPF = 14.7 %) and the 63.2 % drug release time of the drug-carrier composite particles was 15.6 times faster than that of as-received BDP. This study suggests that the drug-carrier composites produced using LTSAA can be employed in the instant formulation of inhalable dry powder.