DEVELOPMENT OF IN-SITU GELLING AND MUCOADHESIVE ACETAMINOPHEN LIQUID SUPPOSITORY

Conventional suppositories are solid forms which often cause discomfor t during insertion. The leakage of suppositories from the rectum also gives uncomfortable feelings to the patients. In addition, when the so lid suppositories without mucoadhesivity reach the end of the colon, t he drugs can undergo the first-pass effect. To solve these problems, w e developed a novel in situ-gelling and mucoadhesive acetaminophen liq uid suppository with gelation temperature at 30-36 degrees C and suita ble gel strength and bioadhesive force. Poloxamer 407 (P407) or/and po loxamer 188 (P188) were used to confer the temperature-sensitive gelat ion property. The mixtures of P407 (15%) and P188 (15-20%) existed as a liquid at room temperature, but gelled at 30-36 degrees C, Acetamino phen, the active ingredient of the suppositories, slightly increased g elation temperature, but significantly decreased gel strength and bioa dhesive force. To modulate the gel strength and the bioadhesive force of acetaminophen liquid suppositories, bioadhesive polymers such as po lyvinylpyrrolidone (PVP), hydroxypropylmethycellulose (HPMC), hydroxyp ropylcellulose (HPC), carbopol and polycarbophil were studied. The bio adhesive polymers exerted various impacts on the physicochemical prope rties of liquid suppositories. The gelation temperature was not signif icantly affected by PVP, HPMC and HPC, but decreased by carbopol and p olycarbophil. Of bioadhesive polymers, carbopol and polycarbophil most significantly enhanced both gel strength and bioadhesive force. The l iquid suppositories with carbopol or polycarbophil were inserted into the rectum of rats without difficulty and leakage and retained in the rectum for at least 6 h. These results suggest that in situ-gelling an d mucoadhesive liquid suppository for humans can be further developed as a more convenient and effective rectal dosage form. (C) 1998 Elsevi er Science B.V. All rights reserved.