| The nootropic drug,aniracetam,is clinically used to treat cognitive dysfunctions,emotional disturbances and behavior abnormalities that are associated with cerebrovascular disease and Alzheimer’s diseases.It has been reported that the bioavailability of aniracetam oral preparations was extremely low probably due to the extensive first-pass effect.The present study,therefore, aimed to improve the bioavailability of aniracetam and to develop an effective aniracetam injection by using submicron fat emulsion system.A high performance liquid chromatography（HPLC）method was established to determine the concentration of aniracetam in the study of physicochemical properties of aniracetam and quality of aniracetam submicron emulsion in vitro.The method was proved to be of high specificity,good precision and excellent method recovery.The solubility of aniracetam in water, different pH phosphate buffers and injectable oils,as well as the apparent partition coefficient of aniracetam in octanol-water system,were determined.The results showed that aniracetam was lipophilic and had good solubility in oil.The study of stability indicated that aniracetam was stable in high temperature,humidity and strong light.Based on single factor test,the formulation was optimized through orthogonal design with appearance,particle size and centrifugation of emulsion as index.The optimal formulation was composed of medium-chain triglyceride 125 g·L-1,emulsifiers 30 g·L-1with a ratio of lecithin and pluronic F68 in 1:4,oleic acid 2 g·L-1,glycerol 25 g·L-1aniracetam 15 g·L-1.The preparation procedure of primary emulsion and final emulsion,effect of pH on stability and method of sterilization were investigated.Finally,the method of agitation of high-speed combined with high pressure homogenization was employed to prepare the aniracetam submicron emulsion.The physicochemical characterization and stability of aniracetam submicron emulsion were studied.The particle size was（149±21）nm,the Zeta potential was -30.8 mV,the pH was 5.86, and the content of aniracetam was 99.2%.The entrapment efficiency was determined by Sephadex and the result was 76.6%.The results of stress test,accelerated test and long-term test suggested that the preparation should be store in a cool place away from light.The formulation and the preparation of lyophilized emulsion were investigated.A combination of 8%mannitol and 2%lactose was appIied after study the protecting effects of various lyoprotectants.The freeze-drying process was as follows:the sample was quickly prefreezed at -75℃for 10 h,primary drying at -35℃for 1 h,-25℃for 14 h and secondary drying at 10℃for 4 h.The quality of the lyophilized product was evaluated.The result showed that lyophilized emulsion was similar with initial emulsion in pH and Zeta potential,but the particle size and distribution was larger than before.An HPLC method was developed for the determination of aniracetam in rat biological samples.With a column of C18,a mobile phase of methanol-water system and aethylparabenum as an internal standard,the method was demonstrated to have good specificity,precision and recovery.Plasma concentration and tissue distribution of aniracetam in rat after iv administration of aniracetam solution and aniracetam submicron emulsion were investigated.The results showed that there were significant differences between the two groups.Compared with solution group,the aniracetam concentration in plasma and tissue of emulsion group wash more igher. Especially,the plasma concentration and the distribution of heart and brain were increased extremely,which suggested that emulsion targeted drug to some tissues such as brain.
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