Study On Indomethacin Extended-Release Pellets Capsules Based On Solid Dispersion

Indomethacin, a non-steroidal anti-inflammatory drug (NSAID), is one of the strongest cyclooxygenase inhibitors. It is widely used, particularly in treatment of rheumatoid arthritis, osteoarthritis, alkylosing spondylitis and other diseases. The elimination half-life of indomethacin is 4.6 h, which is relatively short. Indomethacin is a kind of poorly water soluble drug, so it is possible to administrate a extended-release form. The purpose of this study is to develop a kind of indomethacin extended-release pellets capsules which is based on the solid dispersion technique, would decrease side effects and improve its bioavailability, and be more convenient for patients to use. The drug release behavior and mechanism from capsules were investigated.Indomethacin solid dispersion was prepared from the solution after solvent evaporation, with the carrier of PVPk30. The drug pellet was prepared in centrifugal granulation systerm. The powder property of the pellets was determined well and the yield of objective pellets (30～40 mesh) was about 80%.In this study, Eudragit RS 100 was selected as the coating materials, and alcohol was used as the coating medium, with the technique of fluidized bed. The effects of many factors on the release behavior of indomethacin from extended-release pellets capsules were investigated, including the formulation of the drug pellet and the coating membrane, the arts of preparing extended-release pellets capsules and the drug release condition in vitro.Based on the single-factor experiments, the extended-release pellets capsules were produced by coating with 15% coating amount and 12% PEG 4000. The formulation was optimized according to orthogonal experiment design. The indomethacin release from extended-release pellets capsules was apparently sustained. The investigation of indomethacin release mechanism from extended-release pellets capsules showed that the drug release was primarily controlled by the coated film-membrane. The description of dissolution profiles suggested that among the different kinetics (zero-order, first-order, Higuchi square-root model), the Higuchi square-root model became the most appropriate model to describe release kinetics.A stability analysis method was developed, which indicates that the drug content was stable under high temperature, high humidity and intensive light tests.