Studies On The Sustained Release Suppositor Containing Indomethacin Loaded Microspheres

Indomethacin is a kind of non-steroidal anti-inflammatory drug(NSAID),which has antipyretic analgesic and anti-inflammatory activities by inhibiting the synthesis of prostaglandin. Clinically, it was wide used to treat rheumatoid arthritis and other inflammation. In recent years clinical studies indicated that indomethacin had therapeutical effect on dysmenorrhea, the pains of operation, acesodyne of tumor. In clinic the commercial suppositories had the poor patients' compliance and the unsteadily therapy effect. It's necessary to develop a sustained release suppository with good stability to reduce the frequency of administration and improve patients' compliance.The indomethacin loaded microspheres were prepared by spherical agglomeration technique, which containing Eudragit RS/RL as matrix materials. The orthogonal experiment design was employed to optimize the formulation and technics of microspheres using the drug-releasing rate as evaluation index, which were based upon single factor experiment. The mechanism of indomethacin released from sustained release suppository was investigated. The dissolution data showed that the release followed Higuchi equation and Peppas equation.The sustained release suppositories containing indomethacin loaded microspheres were prepared by fusion method. In vitro dissolution test showed that the release rate of indomethacin from the sustained release suppositories was reduced.A reversed-phase high-performance liquid chromatographic method for the determination of indomethacin in rabbit's plasma was developed. Indomethacin commercial suppository was used as reference to study the pharmacokinetics of sustained release suppository in rabbits. Tmax , MRT were prolonged and Cmax was reduced, at the level of 0.01. Studies showed the self-made suppository can achieve sustained release.