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

<p><b>Context:</b> Dry powder inhaler (DPI) formulations have been developed to deliver large amounts of drugs to the lungs.</p> <p><b>Objective:</b> 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.</p> <p><b>Methods:</b> 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.</p> <p><b>Results:</b> 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 <i>in vitro</i> 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.</p> <p><b>Conclusions:</b> 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.</p