IN-SITU GELLING AND MUCOADHESIVE LIQUID SUPPOSITORY CONTAINING ACETAMINOPHEN - ENHANCED BIOAVAILABILITY

Solutions of poloxamers and bioadhesive polymers were previously repor ted to undergo a phase transition to bioadhesive gels at body temperat ure. For the development of a convenient acetaminophen-loaded liquid s uppository which gels in situ after rectal administration, we studied the release and pharmacokinetics of acetaminophen delivered by the liq uid suppository systems composed of poloxamer P 188, P 407 and a bioad hesive polymer, polycarbophil. The release of acetaminophen was differ ently affected by the components of liquid suppository such as P 188 a nd polycarbophil. P 188 showed little effect on the release rates of a cetaminophen from liquid suppositories. However, polycarbophil signifi cantly delayed the release kinetics of acetaminophen from a certain co ncentration due to strong gel strength and bioadhesive force. The rele ase rates of acetaminophen did not significantly differ between no pol ycarbophil and 0.2% polycarbophil-loaded suppositories, while they beg an to decrease as the concentrations of polycarbophil increased higher than 0.4%. The analysis of release mechanism showed that the release of acetaminophen was proportional to the square root of time, indicati ng that acetaminophen might be released from the suppositories by Fick ian diffusion. Liquid suppository A [P 407/P 188/polycarbophil/acetami nophen (15:19:0.8:2.5%)], which was strongly gelled and mucoadhesive i n the rectum, showed more sustained acetaminophen release profile than did other suppositories and gave the most prolonged plasma levels of acetaminophen in vivo. Liquid suppository A also showed higher bioavai libility of acetaminophen than did the conventional formulation. Moreo ver, liquid suppository A did not cause any morphological damage to th e rectal tissues and remained stable for at least 6 month during stora ge. These results suggest that mucoadhesive and in situ gelling liquid suppository could be a more effective and convenient rectal delivery system of acetaminophen. (C) 1998 Elsevier Science B.V. All rights res erved.