Formulation and Evaluation of In-situ Gelling Tenoxicam Liquid Suppositories

Abstract

The objective of the present study was to develop and evaluate thermoreversible in situ gelling and mucoadhesive liquid suppositories which are liquid at room temperature but forms a gel at body temperature to improve patient compliance and systemic absorption of tenoxicam which is a non-steroidal anti-inflammatory drug (NSAID), exhibited potent anti- inflammatory, analgesic, and antipyretic activity and licensed for use in rheumatic disease and other musculoskeletal disorders. The thermosensitive-mucoadhesive liquid suppositories were prepared by a cold method using poloxamers (P407 and P188) which are used for their temperature sensitive gelation property, and Hydroxy Propyl Methyl Cellulose (HPMC) which is a neutral and swellable polymer, and it was used to modulate gel strength and to impart mucoadhesive force to tenoxicam suppository bases. Sixteen formulations were prepared by the cold method using different concentrations of P407 and/or P188 with or without HPMC. The physicochemical properties of the liquid suppository bases were characterized by their gelation temperature, gel strength, mucoadhesive force, and In-vitro release rate of tenoxicam from prepared liquid suppositories was studied and compared with that from conventional suppository (Epicotil). Only seven formulations showed optimum gelation at body temperature and intermediate gel strength, so they were subjected to the dissolution test. The analgesic effect of tenoxicam-poloxamer gel system was also studied in rats. The results showed that, gelation temperature decreased upon incorporation of the mucoadhesive polymer in the poloxamer solution. Also polymer addition increase the gel strength and the mucoadhesive force of the prepared solutions. The release rate of tenoxicam from liquid suppository was higher than that from conventional suppositories. Analysis of release mechanism showed that the release of tenoxicam from the prepared suppositories was Fickian diffusion. Also the results of in-situ evaluation showed that, the suppositories had a significant analgesic effect (p < 0.05). Among the various formulations examined, the formulations (tenoxicam/P407/P188 (1/25/10 % w/w)) and (tenoxicam/P407/P188/HPMC (1/25/5/1 % w/w)) exhibited the appropriate gelation temperature, gel strength, mucoadhesive force, acceptable drug release and prolonging the latency of the nociceptive response in rats. These results suggested that in situ gelling liquid suppository with tenoxicam, poloxamers and mucoadhesive polymer (HPMC) was a physically safe, convenient, and effective rectal dosage form.