Development of in situ-gelling and mucoadhesive acetaminophen liquid suppository

Abstract

Conventional suppositories are solid forms which often cause discomfort during insertion. The leakage of suppositories from the rectum also gives uncomfortable feelings to the patients. In addition, when the solid suppositories without mucoadhesivity reach the end of the colon, the drugs can undergo the first-pass effect. To solve these problems, we developed a novel in situ-gelling and mucoadhesive acetaminophen liquid suppository with gelation temperature at 30–36°C and suitable gel strength and bioadhesive force. Poloxamer 407 (P407) or/and poloxamer 188 (P188) were used to confer the temperature-sensitive gelation property. The mixtures of P407 (15%) and P188 (15–20%) existed as a liquid at room temperature, but gelled at 30–36°C. Acetaminophen, the active ingredient of the suppositories, slightly increased gelation temperature, but significantly decreased gel strength and bioadhesive force. To modulate the gel strength and the bioadhesive force of acetaminophen liquid suppositories, bioadhesive polymers such as polyvinylpyrrolidone (PVP), hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), carbopol and polycarbophil were studied. The bioadhesive polymers exerted various impacts on the physicochemical properties of liquid suppositories. The gelation temperature was not significantly affected by PVP, HPMC and HPC, but decreased by carbopol and polycarbophil. Of bioadhesive polymers, carbopol and polycarbophil most significantly enhanced both gel strength and bioadhesive force. The liquid 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 and mucoadhesive liquid suppository for humans can be further developed as a more convenient and effective rectal dosage form.