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

Summary: 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 signicant 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.