FORMULATION OF CONTROLLED-RELEASE IBUPROFEN GRANULES AND EVALUATION OF THE ANTIINFLAMMATORY ANALGESIC ACTIVITIES

Abstract

Two kinds of granules were prepared: one. with pH-dependent Release and the other with pH-in dependent release. The former was composed of ibuprofen, celluloseacetate phthalate, ethylcellulose and microcrystalline cellulose while the latter was composed of ibuprofen, hydroxypropyl methylcellulose, ethylcellulose and corn starch. The effects of mixing ratios of the polymers; pH of the release medium, and the drug content in the granules were examined in-vitro to investigate the release characteristics. In granules with pH-dependent, the release rate was decreased with the increment of ethylcellulose and as the pH of the release medium increased. While in granules with pH-independent, the release rate was decreased as the ratio of hydroxypropyl methylcellulose (HPMC) to ethylcellulose (EC) increased Analgesic activity of four seleted formulations of the controlled release was tested by two methods using p-benzoquinone (PB2) induced withing and the hot-plate. Also the anti-inflammatory activity of these formulations was examined after oral administration of the granules by using trypan-blue dye method. Results that the formulation of ibuprofen granules pH-independent containing HPMC and EC revealed in ratio of 3:1 had a delayed onset of anti-inflammatory and analgesic action extended for four hours or more while granules of ibuprofen with pH-dependent containing 4% ethylcellulose and 2% cellulose acetate phthalate were capable of increasing analgesic against thermal stimuli for four hours whereas lower percentage protection against PBO-induced wrifhing, was observed. Statistical analysis of the results were done using student's t-test. The pH- independent release granules were superior to the pH-dependent release granules with respect to prolonging the effective antiinflammatory action when administered orally to rats.