Study Of Poly(Lactic-co-glycolic Acid) Microspheres Containing Ropivacaine

Objective: To prepare ropivacaine mesilate loaded poly(lactic-co-glycolicacid)(PLGA) microspheres.Methods: The accelerated release condition of ropivacaine mesilate loadedPLGA microspheres was established by investigating the effect of vibration frequency,pH of release medium and temperature on ropivacaine mesilate release. Theregression equation was built by correlative evaluation of accelerated release andlong-term release. Ropivacaine mesilate loaded PLGA microspheres were producedby modified W/O/W emulsion solvent evaporation technique. Fundamental preparingconditions such as stirring speed, molecular weight of PLGA, concentration of PLGAand etc were investigated. Three independent variables including concentration ofPLGA, stirring speed and theoretical drug loading were optimized by orthogonaldesign. Dependent variables or responses investigated in this study were burst effect,loading efficiency, drug loading, release and etc. The optimized levels were obtainedby visual analysis. Prescription were optimized by orthogonal design，the qualities ofmicrosphere were evaluated，including reproducibility, amplification experiment, andthe stability,in order to investigate the possiblity of industrialization. studied thepharmacokinetics in Sprague Dawley(SD) rats and its pharmacodynamic preliminary.Results: Accelerated release was correlated well with long-term release (r2=0.9880). Accelerated release method could be applied to evaluate the drug releaseprofile of ropivacaine mesilate PLGA microspheres in shorter time. It was shownfrom SEM that the microspheres was spherical and the surface of microspheres wassmooth., The drug loading percent was25%, the entrapment efficiency was95%，andthe yield was about85%. By the study of drug release in vitro, it was shown that the microspheres could release lidocaine sustainedly for7days. The release kinetics oflidocaine from PLGA-MS in vitro can be described by Ritger-peppas equation. Therepeated tests were stable and repeatable. It was indicated that the microspheres wereunstable under high temperature or highlighted conditions and should be kept fromheat and light. There was no difference in the microspheres placed in the acceleratedtests for one month. Pharmacokinetics parameters were calculated by3P97software.The in-vivo results indicated that the microspheres preparation had the role ofsustained release and its relative bioavailability was higher than95%, and had betterrelieve pain effects.Conclusion: Accelerated release method could be applied to evaluate the drugrelease profile of ropivacaine mesilate PLGA microspheres in shorter time. It wasshown from SEM that the microspheres was spherical and the surface of microsphereswas smooth. The repeated tests of the optimized levels proved that the technology andformula were stable and repeatable. The in-vivo results indicated that themicrospheres preparation had the role of sustained release and its relativebioavailability was higher than95%, and had better relieve pain effects. Thepreparation of microspheres was proved a candidate of new drug.