Study Of Poly(Lactic-co-glycolic Acid) Microspheres Containing XG-07 For Injection

XG-07 is a new atypical antipsychotic XG-07 vailable for schizophrenia management. Modest improvements in negative and to a lesser extent, cognitive symptoms have also been demonstrated, with diminution of positive symptoms, lower dosage and better safty. Despite these gains, the administration of atypical antipsychotic is still oral pill or oral solution. As a special group of patients with schizophrenia, it may be difficult for them to take that regularly. This paper will combine this new kind of atypical antipsychotic XG-07 and new drug delivery system microsphere to a new administration of XG-07: extended release microspheres.First, we studied the feasibility of the plan in theory, then we prepared microspheres by solvent evaporation method. We studied methods that used to determine the drug loading and content of accumulatived release of microspheres. We examined the self-made menstruum of microspheres, and found they were effective and feasible. A specific and sensitive HPLC-MS method for the determination of XG-07 in rats'plasma was described. PLGA microspheres of XG-07 were used to study the pharmacokinetics in rats. The results showed that: Correlation researches showed that: the vivo release of self-prepared XG-07 could be well correlated with the vitro release as well as the accelerated release, so the accelerated release could be applied to confer the vivo release.We researched fundamental preparing conditions such as stirring speed, molecular weight of PLGA and concentration of PLGA, therotical drug loading, utensils 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. In this study ,we evaluated the physicochemical properties of the microspheres .The micropheres were good fluidity and the surface morphology was spherical . The average particle size was about 70-80μm. The average drug loading and the encapsulation efficiency were about 30% and 90% respectively. 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 two months indicated that the release speed of the preparation was higher than reference standard, but there was no distinct difference between them.Overall, the preparation of microspheres was fit for muscle injection and proved a candidate of new drug.