Preparation And Pharmacodynamic Evaluation Of Ivermectin And Praziquantel Nanoemulsion

Objective: Preparing ivermectin&praziquantel Nanoemulsion and studied its stability, safety andtherapeutic efficacy.Method:(1) Determined the oil and cosurfactant according to the solubility of ivermectin andpraziquantel in them, screed the surfactant and Kmby studying the pseudoternary phase diagram. Thestructure type, shape and particle diameter distribution of IVM-PZQ nanoemulsion were investigated bystaining method, transmission electron microscope and laser particle size analysator respectively. Itsstability was verified through high speed centrifuge, accelerated test and long term experiment.(2)Theanalytical method of ivermectin and praziquantel was established by high performance liquidchromatography (HPLC) method. The method’s specification recovery rate and precision were inspected,standard curve was drawed.(3) Evaluating the safety and antibacterial activity through acute toxicity testand broth dilution method respectively.(4)The high, medium and low dose of IVM-PZQ nanoemulsion,ivermectin was respectively dosed to the rabbits which were infected by acarid and the therapeutic efficacyin vivo was investigated.(5) The high, medium and low dose of IVM-PZQ nanoemulsion, praxiquantel wasrespectively dosed to the Sally-Can milk goats which were infected by Fasciola lanceolata and thetherapeutic efficacy in vivo was investigated.Result:(1) The mass fraction of the components in IVM-PZQ nanoemulsion was ivermectin0.03%0.03%,5%praziquantel, castor oil, polyoxyethylene hydrogenated castor oil (RH40)30%, propyleneglycol, distilled water,7.5%and46.67%. IVM-PZQ nanoemulsion was yellow, transparent, homogeneousand oil-in-water nanoemulsion. The shape of the nanoemulsion drop was spherical and the average particalsize was15.8nm. IVM-PZQ nanoemulsion was stable after high speed centrifuge, accelerated test and longterm exper-iment.(2) Standard curve equation of ivermectin is:11760x+Y=11760. Ivermectinreference solution concentration shows good complicity in0.5～25μg/mL; Standard curve equation ofpraziquantel is: Y=230439X+1024. Praziquantel reference solution concentration shows good complicity in40～200μg/mL;(3) The oral acute toxity test for mice suggested that the nanoemulsion was low toxitywith LD50ranged3207mg/kg.(4) The cure rate of IVM-PZQ nanoemulsion in high, medium,low dosegroup and ivermectin group was80%,40%,20%,40%respectively.(5) The deminution of worm eggs rateof IVM-PZQ nanoemulsion in high, medium、low dose group and praziquantel group was97%、84.8%、45%、47.1%, respectively, and the negative of worm eggs rate of IVM-PZQ nanoemulsion inhigh, medium、low dose group and praziquantel group was80%、40%、0、0. Conclusion: The prepared IVM-PZQ nanoemulsion has good stability, safety and better therapeuticefficacy than Ivermectin injecta and praziquantel tablet sold in the market, which would have wide prospectin clinical application.