注入時に優れた摺動性能を有する徐放性ポリ乳酸・グリコール酸共重合体懸濁注射製剤の開発

抄録

A sustained-release injectable formulation with polylactic acid-glycolic acid (PLGA) copolymer particles was developed. The suspension of the formulation dispersed in injection fluid provided excellent gliding performance when extruded from the syringe. The PLGA microparticles (MRPs) with aripiprazole (ARP), as a model drug in this study, were prepared by a spray-dryer. The resultant MRPs were entrapped in a granular matrix composed of water-soluble additives and a surfactant through a drop freeze-drying process to design the granulated microparticles (G-MRPs). In this study MRPs and G-MRPs were evaluated for their physicochemical and pharmaceutical properties. It was found that the MRPs, which were spherical particles approximately 1-20 μm in size, were strongly aggregated in the aqueous phase. The clogging of a needle hole was frequently observed while discharging MRP suspension from the syringe, resulting in increased gliding force up to around 5 kgf, which was detected by extrusion force. On the other hand, the G-MRPs were spherical granules 200-400 μm in size, and had a microparticles-in-granule structure in which the MRPs were embedded in the porous matrix inside the granule. Unlike the MRPs, the G-MRPs had excellent needle passagability with tolerant gliding force, which was attributed to the nearly mono-dispersibility of the MRP particles in the injection fluid. ARP release behavior from G-MRPs could be controlled by changing PLGA:ARP ratio, which indicated a potential for development of a depot-type injectable formulation. In addition, the G-MRPs had excellent powder properties, suggesting that the current granulated MRP solid dosage form would contribute to automatic filling into a pre-filled syringe.