[Optimization of Preparation, and Stability of Indomethacin Mouth Wash for Oral Mucositis Caused by Cancer Therapy].

OBJECTIVE: Severe oral mucositis caused by chemo- and radio-therapy is a common adverse event in patients with cancer. In this study, we investigated the development of an indomethacin mouth wash(IM-MW)as a novel approach to treat pain due to oral mucositis. METHODS: We examined the appropriate preparation methods for IM-MW with suitable stability. IM- MW was made from bulk IM, controlled release IM capsules, and IM capsules. Dissolution in water was tested at water temperatures of 70℃, 90℃, and 98℃(n=3), and with a shaking time of 30 or 60s(n=3). We determined the IM concentration in IM-MW by HPLC-UV analysis(n=5)at time points between just after preparation and day 7, to estimate the shelf- life at 4℃ and 25℃. RESULTS: At 70℃, bulk IM did not dissolve, but at 90℃ and 98℃, bulk IM, controlled release IM capsules, and IM capsules all dissolved effectively. Shaking times of 30 and 60s were sufficient to dissolve bulk IM, controlled release IM capsules, and IM capsules. The stability of IM in IM-MW was 98.6+/-2.8%(bulk), 99.2+/-6.0%(controlled release capsule), and 98.5+/-6.0%(capsule)over 7 days at 4℃. However, at 25℃, IM stability in IM-MW decreased to 95.3+/-1.8% (bulk), 86.1+/-4.8%(controlled release capsule), and 83.6+/-1.6%(capsule). CONCLUSION: In this study, we identified the most suitable method for the preparation of IM-MW(90℃, shaking time of over 30s). IM-MW was stable when stored at 4℃ for at least 7 days after preparation.