抄録
Mucositis, a common adverse event in anti-cancer treatments such as chemotherapy and/or radiotherapy, accompanies severe pain resulting in poor quality of life. Indomethacin (IM), a non-steroidal anti-inflammatory drug (NSAID), is one of the therapeutic options as a spray preparation (0.25% IM dissolved in phosphate buffer, pH 7.4) for pain control of oral mucositis. The stability of IM and the production of its degradative compounds are unclear in spray preparation. The aim of this study was to assess the stability of IM-spray preparation by determining the concentration of IM and its degradation products, 5-methoxy-2-methylindole-3-acetic acid (MM) and p-chlorobenzoic acid (CB). IM-spray preparation was stored under room temperature (25°C) or a cycling of room and refrigerator (4°C-25°C, each 12 hour) for 4 weeks. Under room temperature storage, IM concentration in the preparation decreased from 2.48 mg/mL to 2.29 mg/mL and MM and CB increased from an undetectable level to 0.12 and 0.06 mg/mL, respectively, a week after starting the study. Under the cycling of room and refrigerator, reduction of IM and the elevation of MM and CB in the spray preparation were also observed for a week's storage, though the magnitude was smaller (IM: from 2.48 mg/mL to 2.36 mg/mL, MM/CB: 0.06/0.03 mg/mL) when compared with the room temperature conditions. The time variation on the residual ratio of IM in the spray preparation at 4°C and -20°C was greater than 98.4% for 2-24 months' storage. Freezing and thawing did not affect IM concentration in the spray preparation until ten repetitions. The present results led to the conclusion that IM-spray preparation should be kept in a refrigerator for daily use and could be stored for at least 2 months at 4°C and 24 months at -20°C.
