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.

Aphthous stomatitis is induced by chemotherapy and radiotherapy. It has been reported that 100% of patients administered high-dose chemotherapy, 80% of patients receiving radiotherapy, and 40% of patients receiving 5-FU-based chemotherapy develop stomatitis. The most serious cases are accompanied by pain and bleeding of ulcers, which cause significant suffering and reduce the patient's quality of life. Mouth washes and ointments are usually used in the treatment of stomatitis in Japan. Rebamipide (RB) was developed in Japan as a medicine for gastric ulcer. In this study, we prepared and evaluated a mouth wash for stomatitis taking into consideration the solubilization of RB. RB nanoparticles were prepared by the wet-milling technique using various hydroxypropyl cellulose (HPC-L, HPC-SL and HPC-SSL) and sodium lauryl sulfate (SLS). Various RB nanoparticle having in particle size between 126.6 and 286.8 nm could be obtained under various conditions. From the measurement of zeta potential measurement, it appeared that the prepared nanosuspension was stable. Furthermore, adhesion properties of nanoparticles to the mucous membrane in the oral cavity were evaluated using quartz crystal microbalance with dissipation monitoring (QCM-D) technology. From the changes in thickness of the gold sensor observed in QCM-D measurment, it was suggested that HPC-SSL molecules interact with mucin mounted on the gold sensor. From these results, the RB nanoparticle dispersed in HPC-SSL solution seems to be feasible to apply the mouthwash to prevent the stomatitis.