[Development of Hospital Formulations Based on Medical Need]

Abstract

Aphthous stomatitis is induced by chemotherapy and radiotherapy. It has been reported that 100% of patients administered high-dose chemotherapy and 80% of patients receiving radiotherapy develop stomatitis. The most serious cases are accompanied by pain and bleeding of the ulcers, which cause significant suffering and reduce patients' quality of life. Rebamipide (RB) was developed in Japan as a treatment for gastric ulcer. In this study, we prepared and evaluated a mouthwash for stomatitis taking into consideration the solubilization of RB. RB nanoparticles were prepared by the wet-milling technique using various forms of hydroxypropyl cellulose (HPC-L, -SL, and -SSL) and sodium lauryl sulfate (SLS). RB nanoparticles sized between 126.6 and 286.8 nm were obtained under various conditions. From the results of zeta potential measurement and evaluation of their dispersibility, it appeared that the prepared nanosuspensions were stable. Furthermore, adhesion of the nanoparticles to the mucous membrane in the oral cavity was evaluated using quartz crystal microbalance with dissipation monitoring (QCM-D) technology. From the changes in the thickness of the gold sensor observed in QCM-D measurement, it was suggested that HPC-SSL molecules interact with mucin mounted on the gold sensor. It appears feasible to utilize RB nanoparticles dispersed in HPC-SSL solution in mouthwash to prevent stomatitis.

Keywords: dispersion; medical need; nanoparticle; rebamipide; stomatitis.