DEVELOPMENT OF IN SITU GELLING AND MUCOADHESIVE MEBEVERINE HYDROCHLORIDE SOLUTION FOR RECTAL ADMINISTRATION

Abstract

,An investigation of the ethanolic extract of the pods of Albizzia lebbeck (L.) Benth. afforded a Mebeverine hydrochloride (MbHCl) is well known to suffer from extensive first pass effect. In an attempt to improve its bioavailability and possibility restrict its absorption to only the lower rectum, rectal solution with gelation at temperature range of 30-37C o . Mixtures of poloxamer 407 (P407) and poloxamer 188 (P188) were used to confer the temperature-sensitive gelation property. To modulate the gel strength and the mucoadhesive force of MbHCl poloxamer rectal solution, mucoadhesive polymers such as hydroxypropylmethyl cellulose (HPMC), hydroxyethyl cellulose (HEC), methyl cellulose (MC) and polyvinylpyrrolidone K-25 (PVP K-25) were investigated. Incorporation of 10% w/w MbHCl in the rectal solution increased the gelation temperature of the poloxamers mixtures, while the addition of the mucoadhesive polymers had a reverse effect. On the other hand, these polymers reinforced the gel strength and the mucoadhesive force of the prepared solutions. The effect was most pronounced with MC. Increasing the concentration of cellulosic bioadhesive polymers retarded the release of MbHCl from the poloxamer solutions to different extents, and it was possible to sustain the drug effect over a period of 8 hours. PVP K-25 had no effect on drug release. Pretreatment of guinea pigs with MbHCl rectal solution [P407/ P188/ MC/ MbHCl (23/ 7/ 1.5/ 10% w/w)], having satisfactory gel strength, mucoadhesive properties and acceptable sustained release profile with zero order release kinetics, showed a significant extended spasmolytic effect to spasmogens-induced contractions on guinea pig ileum and did not cause any histological damage to the rectal tissues.