Investigation And Evaluation Of Nano-Albendazole Dry Suspension In Vitro And In Vivo

Objective: According to the requirements of preclinical research on new pharmaceutical preparations,the physical and chemical properties of nano-albendazole dry suspension were first investigated,and its quality standards,stability,pharmacokinetics and pharmacodynamics were studied to develop a new The foundation of anti-hydatid preparations.Methods:(1)Based on the preparation of the nano-albendazole dry suspension in the previous research group,the properties of the nano-albendazole dry suspension were investigated.The indicators of inspection were appearance,fluidity,bulk density and dispersion,and dissolution.Degree,morphology,particle size,potential,p H value,sedimentation volume ratio,redispersibility(2)With reference to the relevant provisions of the "Dry Suspension" and "Particle Preparation" of the 2015 edition of "Chinese Pharmacopoeia",the appearance,particle size and distribution,weight loss on drying and sedimentation volume ratio of the preparation were inspected to establish the nanometer albendazole quality standards of suspensions.(3)With reference to the "Guidelines for Drug Stability Testing" of the 2015 edition of the Chinese Pharmacopoeia,according to established quality standards,the factors affecting the stability of nano-albendazole dry suspensions were investigated.Then,accelerated tests and long-term tests are conducted to examine the stability of the formulation.(4)Firstly,the method for determining the content of albendazole and its metabolites in rats was established by UPLC-MS / MS method,and then the albendazole raw powder was used as a control group,and a single dose of nano-albendazole was determined for dry suspension.The plasma concentration of albendazole in rats and the concentration of albendazole in liver and lung tissues were compared for pharmacokinetic parameters and tissue concentrations.(5)Taking the albendazole bulk drug as a control group,the effects of nano-albendazole dry suspension gavage for 4,6,and 8 weeks on the mouse model of echinococcosis were observed to conduct a preliminary pharmacodynamic evaluation.Observation indicators were cyst wet weight,cyst suppression rate,liver tissue and vesicle pathology,cyst wall ultrastructure,and albendazole concentration in cyst fluid.Results:(1)The physical and chemical properties of nano-albendazole dry suspension before and after hydration meet the relevant requirements of the 2015 edition of "Chinese Pharmacopoeia" "Dry Suspension" and "Particle Preparation".(2)The established quality standards are as follows: the appearance is white powder,the color reaction of bismuth potassium iodide is positive,the maximum(minimum)absorption is at 295nm(277nm),the loss on drying is not more than 2%,and the sedimentation volume ratio is not less than0.98.The particle size and its distribution are less than 500 nm and the distribution is uniform,and the albendazole content is 90-100% of the dosage.(3)Humidity can affect the stability of nano-albendazole dry suspension.The nano-albendazole dry suspension has undergone accelerated and long-term tests for 6 months,respectively,and its indicators have not shown significant changes.(4)Through statistical analysis,the pharmacokinetic indicators represented by the bioavailability of the nano-albendazole dry suspension are better than the albendazole raw material powder,and the albendazole concentration in liver and lung tissues are also uniform higher than the albendazole raw material powder,and all have significant difference(P <0.05)s.(5)Through statistical analysis,the vesicle wet weight of the nano-albendazole dry suspension in each dosage group and each cycle was less than that of the albendazole raw material powder administration group,which had a dose-effect and time-effect relationship with statistical differences(P <0.05).At the same dose,the cyst suppression rate and the concentration of albendazole in the hydatid cyst fluid of each nanometer albendazole dry suspension were significantly greater than that of the albendazole API(P <0.05).The liver tissue and vesicle pathology and the ultrastructure of the cyst wall also showed that the nano-albendazole dry suspension was superior to the abendazole raw material in the anti-hydatid effect.Conclusion:(1)The physical and chemical properties of nano-albendazole dry suspension meet the relevant requirements and provide a reliable basis for the research of new pharmaceutical preparations.(2)The established quality standards are feasible and the quality is controllable.(3)The stability of the preparation for 6 months is good,which provides a preliminary basis for the selection of prescription technology and packaging materials.(4)The bioavailability and liver and kidney tissue distribution of the preparation were significantly higher than those of albendazole raw material powder.(5)The experimental results suggest that the effect of the preparation on hydatid disease is significantly higher than that of albendazole raw material powder.