Preparation Process And In Vivo Study Of Perphenazine Sustained-release Microspheres

As white or pale yellow crystalline powder,perphenazine is a piperazine derivative of phenothiazines.Clinically,it is an antipsychotic drug,used for schizophrenia or other psychotic disorders.Perphenazine has a strong side effect.Polyethylene glycol is a water-soluble,biodegradable,and non-toxic polymer.Polyethylene glycol grafted perphenazine microspheres were prepared,which reduce release rate and plasma concentration of perphenazine,and then reduce adverse reactions.In this paper,polyethylene glycol grafted perphenazine was synthesized by chemical method.Firstly,hydroxyl group of perphenazine was activated via an acylation reaction.Secondly,polyethylene glycol grafted perphenazine was prepared by esterification with polyethylene glycol 6000.The synthesized grafts were characterized by IR and NMR.At last,polyethylene glycol grafted perphenazine sustained-release microspheres were prepared by solvent evaporation method.The preparation parameters of microspheres were optimized by the response surface design method.The optimum preparation conditions were as follows: the concentration of polyethylene glycol grafted perphenazine was 87.50 mg/mL,the volume ratio of dispersed phase to continuous phase was 1:12.5,the emulsification speed was 12500 rpm,Span-80 concentration was7.5 mg/mL,and solvent was volatilized at 600 rpm for 6 h.Perphenazine concentrations were determined by high performance liquid chromatography.The pharmacokinetic study of polyethylene glycol grafted perphenazine sustained-release microspheres was performed by subcutaneous administration of oil-soluble suspensions in mice.The results showed that perphenazine was released steadily from microspheres,and plasma concentration-time curve fluctuated within a narrow range and last for more than 20 days.In a word,the prepared microspheres have a good sustained-release effect.