Studies On Loxoprofen Sodium Sustained Release Tablets

Loxoprofen sodium (Lox), a non-steroidal antinflamma tory drug(NSAID), has maked analgesic and antiphlogistic activeities. It has been mainly used for chronic rheumaticsm arthritis, deformability arthritis, lumbag, scapulaihumeral periarthritis, neck shouder syndrome and analgesic antiphlogistic after operation and tooth extratiom. For plain tablets, the usual administration was 60mg 3times daily. Frequent adminstrations led to fluctuation in blood concentration and high incidence of adverse effects. Therefoe it was necessary to prepare a kind of sustained release preparations. Combining with other filers, a sustained release tablet(SRT) of twice daily administration was prepared by using hydroxypropyl methyl-cellulose and hydroxypropyl chitosan as basic matrix material.According to the literature, UV spectrotometry which is selective and sensitive was developed for the determination of loxoprofen sodium during the study of release. We also developed a HPLC method for the determination of the drug content of the tablet and the preformalation study. The method was quick and accurate which could meet the requirement of the analysis.In the preformulation studies, the physicalchemical properties were investigated. The drug solubility in various media and appearant oil-water partition coefficient was determined.Following the principles on the prolong-released and controlled-released preparation in appendix XDCD, CHP 2000, and basing on the results of single-factors tests, orthogonal design test was carried out to optimize the formulation and the optimal tablet administrated twice a day was screened. Stability studies of loxoprofen sodium-SRT showed that temperature and air had little effect on the content and release behavior of the drug, while moisture is not.On the basis of pharmaceutical pre-formulation studies, the preparation technique and optimized formulation of loxoprofen sodium-SRT, which extend the drug release to 12 hours in vivo, were determined by single-factor test and orthogonal design test. The test of quality and the basic stability of three batches of tablets prepared by optimized formulation were carried out. The Higuchi model were used to study the release mechanism, some factors which had great influence on the release were investigated. Finally drug release mechanism was con-firmed as a combination result of diffusion and erosion, but diffusion was main part of them.