Abstract
Rofecoxib, a practically insoluble cox-2 selective nonsteroidal antiinflammatory agent was subjected to improvement in solubility by preparing its binary mixtures with β cyclodextrin using various methods such as physical mixing, co-grinding, kneading with aqueous methanol and co-evaporation from methanol-water mixture. Characterization of the resulting binary mixtures by differential scanning calorimetry and X-ray diffraction studies indicated partial amorphization of the drug in its binary mixtures. In vitro dissolution studies exhibited remarkable increase in rate and extent of dissolution of the drug from its complexes with β -cyclodextrin. Pure rofecoxib as well as its co-ground binary mixture were formulated as aqueous gels for topical application. In vitro skin permeation of rofecoxib from formulation containing rofecoxib-cyclodextrin complex was significantly higher (p<0.05) at 1, 2, 12, 18 and 24 hr as compared to formulation containing pure rofecoxib. This could be attributed to better solubility of binary mixture in the aqueous gel vehicle leading to greater concentration gradient between the vehicle and skin and hence higher flux of the drug.
Highlights
Rofecoxib (RXB), a cyclooxygenase -2 speciÞc nonsteroidal antiinßammatory drug (NSAID) is indicated for the relief of signs and symptoms of osteoarthritis, rheumatoid arthritis and management of pain in adults[1]
Treatment of arthritis generally involves long term therapy with NSAIDs, chronic oral administration of which is associated with undesirable side effects especially gastrointestinal (GI) disorders
The aim of the present study was to evaluate the inßuence of β-cyclodextrin (BCD) on the solubility and in vitro dissolution characteristics of RXB as well as on the in vitro skin permeation of the drug when formulated into an aqueous gel
Summary
Co-evaporated BM (COEVAP) was prepared by dissolving RXB in methanol and BCD in water, following which both the solutions were mixed and the solvent mixture was evaporated by controlled heating at 45-50o with continuous stirring of solution until dry. Assay and in vitro dissolution studies: Each BM equivalent to 12.5 mg of RXB was weighed accurately and dissolved in 25 ml of methanol by sonication; 1 ml of this solution was diluted to 100 ml with 0.1 N HCl containing 0.5% polysorbate 80 (Tween 80). Prepared gel base was added to the slurry of RXB or BM and mixed using an overhead stirrer (Remi, Mumbai) for sufficient time to get a homogeneous white colored gel formulation. Chromatograms were obtained by injecting samples on to the system equipped with 20μl loop and C18
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