Development and Characterization of a Suspension Containing Nanoparticulated Rebamipide for a Mouth Wash for Stomatitis

Abstract

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.