DPI Formulation Development of a Water-Insoluble Drug and a Large Scale Manufacturing

摘要

A small molecular weight novel drug candidate wasdeveloped as dry powder inhalation (DPI) formulationsand we have tried to set up large scale manufacturingconditions of the DPI formulation by spray-dryingmethod for making powders of clinical trial supplies.Typical DPI formulation techniques, for example,micronization of drug substance alone or blending withlactose were not effective for this compound to achieve agood inhalation performance evaluated by FPF (fineparticle fraction) and FPD (fine particle dose) since thepowder has very sticky nature and the drug loading wasvery high. As a consequence, we employed finepulverising methods using wet-milling and jet-milling incombination with spray-drying technique. The optimizedpowder formulations showed good inhalationperformance in vitro testing. (FPD >50%)In order to manufacture clinical trial supplies, weestablished scale-up spray-drying process from laboratoryequipment to large scale cGMP manufacturing facility.