Study Of Poly (Lactic-co-glycolic Acid) Microspheres Containing Dexamethasone Acetate For Intra-articular Injection

Study of Poly(lactic-co-glycolic acid) microspheres ContainingDexamethasone Acetate for Intra-articular InjectionSupervisor: professor Mei XingguoM.S Candidate:Li Zhiping Arthritidis are common and chronic diseases, and there is about 10% of thepopulation in our country suffered from these diseases. As with nonsteroidal anti-inflammatory drugs (NSAIDs), side effects such as gastrointestinal mucosal damage, irritation and bleeding etc are severe, dexamethasone acetate is commonly utilized in the treatment of arthritidis as an effective adrenal cortical hormone with low aftereffects. But patients must tolerate frequent injections and severe side effects of common preparations. So they are prone to accept such therapy if dexamethasone acetate is delivered chronically and locally.Microcapsules, liposomes, microemulsions, nanoparticles and microspheres etc are popular forms for sustained release. Of these forms, biodegradable microspheres are commonly used. Poly (lactide-co-glycolic acid) (PLGA), a copolymer of poly(lactic acid) and poly (glycolic acid ), has been studied extensively as a polymeric carrier for biodegradable microspheres. Thus, mainly due to their long history of safe human use in the form of surgical sutures and their commercial availability in various monomer ratios and molecular weights, a wide variety of drugs ranging from small molecular weight therapeutic agents to peptide hormones, antibiotics and chemotherapeutic drugs have been studied using these biodegradable polymers. From all these, the preparation of PLGA microspheres to extend release time of dexamethasone acetate for intra-articular injection were designed.First, we studied the feasibility of the plan in theory, then we prepared microspheres by solvent evaporation method, we researched fundamental preparing conditions such as stirring speed, molecular weight of PLGA and ratio of GA and LA, concentration ofAbstractPLGA, therotical drug loading, utensils, the ratio of two inner phase solvents and etc. Three independent variables including concentration of PLGA, therotical drug loading and the ratio of two inner phase solvents were optimized by orthogonal designs. Dependent variables or responses investigated in this study were loading efficiency, drug loading, burst effect, mean diameter, span of dispersity and etc.The optimized levels were obtained by visual analysis. The repeated tests of the optimized levels proved that the technology and formula were stable and repeatable. The enlarged test indicated that the preparation could be produced in bathes by factory.The microspheres made in this study were loaded in ampoules and were tested unstable factors. It was indicated that the preparation were unstable under high temperature or highlighted conditions, so it should be kept from heat and light. The results of accelerated tests in three months indicated that the release speed of the preparation was higher than reference standard, but there was no distinct difference between them. In the long term tests of three months, microspheres were almost identified with reference standard.To investigate the characters of microspheres in rabbit, we examined Y -ray radiation sterilization and the self-made menstruum of microspheres, and found they were effective and feasible. Pharmacokinetic parameters and relative bioavailability were evaluated in New Zealand rabbit with injection of dexamethasone acetate suspension as reference standard. The data were managed using 3p87 pharmacokinetic program, and the results indicated that the microsphere preparation had the role of sustained release and its relative bioavailability was higher than 100%.Overall, the preparation of microspheres was fit for intra-articular injection and proved a candidate of new drug.