The Development Of HR-5Osmotic Pump Controlled-release Tablets

HR-5as non-ergot drug can effectively and selectively excite nigra-striatumdopamine D2receptor of the brain. Two formulations had been put into the market byGSK company. Compared with traditional tablets, controlled-release matrix tabletsproduced by geomatrix controlled-release patent have many advantages, but they aretoo difficult to imitate using common matrix technology. So we adopted elementaryosmotic pump technology to delivery HR-5with enough investigation, and the observeddosage have no significant difference with reference tablets in release kinetics in vitroand pharmacokinetics parameters in vivo.The pre-formulation research was conducted on the basis of scientific literatures.Firstly, some physico-chemical property and maximum absorption wavelength of HR-5were obtained. Then the method of detection release, content and releated imputies wereestablished, all results of verification indicated that these methods are sensitive, accurateand reliable for quality control of the formulations.Based on the study of pre-formulation, we used single factor method and f2values tostudy the factors influenced drug release, such as osmotic agents, block agents, adhesiveagents, orifice, pore forming agents and membrance thickness. At the same time, thepreparation technologies were also studied. The correlation between pressure and size oftablets and drug release was studied. The correlation between temperature, atomizationpressure, flow rate of coating solution and membrance quality was studied by highperformance coating machine. The release accumulation, content and releated imputiesof three batches tablets produced by optima formulation were detected, and the resultsimplied the optima formulation was rational and scientific.The influencing factors test, accelerated test and long-term test were carried out toinvestigate the stability of osmotic pump tablets of HR-5. Influencing factors test complied with the quality standard, which suggested that the tablets should be stored atroom temperature and dry place. The results of accelerated test and long-term testindicated that the tablets are stable at three months after preparation.Using LC-MS/MS to determine the plasma drug concentration, the study ofpharmacokinetics of three formulations was carried out in beagle dogs. Compared withcommon tablets and matrix tablets, osmotic pump tablets have lower C_maxand longerMRT and relative bioavilabilty was107.2%. The correlation between absorption in vivoand percentage of drug dissolved in vitro was demonstrated better by linear regressionanalysis.