Study On Injectable Microspheres Of Asenapine Maleate

ObjectiveTo prepare asenapine microspheres which were dispersible,homogenous and could be released at uniform or near uniform for a long time.ASM microspheres will be prepared by mechanical stirring method,SPG membrane emulsifieation and microfluidic technology,and the prescriptions and processes are investigated and optimized.MethodsA high performance liquid chromatography(HPLC)method was established as an in vitro quantitative method for ASM.Wi th the PLA as the polymer carrier,the entrapment efficiency,drug loading,particle size and span,and in vitro release behavior of the microspheres were taken as the index.The method of single factor was used to determine the formulation of ASM microspheres.Polymers,mixed polymers and microsphere curing process were optimized for the best polymer materials and microspheres curing conditions.ASM microspheres were prepared by SPG membrane emulsification and microfluidic technique respectively,the optimum preparation method was selected by comparing with the mechanical stirring method.The pharmacokineties of ASM microspheres in beagle dogs was studied and the in vitro and in vivo correlations were investigated.ResultsAccording to the methodological verification,the IIPLC method establ i shed in this experiment meets the requirement of content determination and could be used for the determination of ASM content.By observing the equilibrium solubility of ASM in different buffers,it was found that ASM had the lowest solubility in 0.05 M sodium bicarbonate solution at pH 7.8,and this buffer was used as a solution to dissolve PVA to enhance the encapsulation of microspheres.The ASM microspheres had high encapsulation and wide particle size distribution and the drug was slowly released in 28 days,which prepared by mechanical stirring method with PLA 25K.The results of the optimization of the prescriptions and processes showed that the ASM microspheres prepared with PLGA 75/25 at the ratio of 1:5 were able to release the drug into the medium at a uniform rate or close to uniform within 40 days.The experimental results showed that the membrane emulsification method could improve the entrapment efficiency of microspheres and make the particle size distribution of microspheres more concentrated,but the spherical shape of microspheres was not complete.In addition,microfluidic technique is used to prepare high encapsulation,monodisperse,uniform particle size,spherical rounded,smooth surface,dense structure,and could slowly release the drugs within 40 days.The pharmacokinetic study of ASM microspheres in beagle dogs showed that ASM microspheres had a small amount of burst release on the first day and decreased to steady state concentrations before 9 days until 28 day.The in vitro and in vivo correlation studies showed that ASM microspheres had a good correlation with in vitro release and release behavior in beagle dogs,so in vitro release test could be used to evaluate in vivo release behavior of microspheres.ConclusionIn this study,ASM microspheres were prepared by microfluidic technology,which were high encapsulation efficiency,monodisperse,uniform particle size,spherical rounded,smooth surface,dense structure,and could achieve stable and complete in vivo release of the drug within 28 days.It was a good research significance and application prospect that this became the first ASM microspheres preparation,...