Appropriate selection of an aggregation inhibitor of fine particles used for inhalation prepared by emulsion solvent diffusion.

ABSTRACT

CONTEXT Dry powder inhaler (DPI) formulations have been developed to deliver large amounts of drugs to the lungs. OBJECTIVE: Fine particles of a poorly water-soluble drug, the model drug ONO-2921, were prepared by the emulsion solvent diffusion (ESD) method for use in a DPI. METHODS: The effects of additives on the fine particle formation of ONO-2921 were estimated when droplets of an ethanolic drug solution were dispersed into aqueous media containing various additives. Subsequently, the suspensions were freeze-dried to create powdered samples to estimate the inhalation properties using a twin impinger and an Andersen cascade impactor. RESULTS: This simple ESD method produced submicron-sized ONO-2921 particles (approximately 600 nm) in combination with suitable additives. In addition, the freeze-dried powder produced using additives exhibited superior in vitro inhalation properties. Among these methods, the freeze-dried powder produced with 0.50% weight/volume one type of polyvinyl alcohol (PVA-205) displayed the most efficient features in the fine particle fraction (FPF). These results could be explained by the stabilization of the ONO-2921 suspension by PVA-205, indicating that PVA-205 acts as an aggregation inhibitor of fine particles. CONCLUSIONS: The ESD method, in combination with appropriate types and amounts of additives, may be useful for preparing a DPI suitable for delivering drugs directly to the lungs without the assistance of carrier particles.