Preparation And Pharmacodynamic Evaluation Of Cefixime Nanoemulsion

Objective: In this tsudy, we prepared the cefixime nanoemulsion and studied its quality,stablity, toxicity and therapeutic efficacy, providing experimental basis for application inveterinary clinic.Method:(1) We determined the solubility of cefixime in different oil, prepared cefiximenanoemulsion by useing pseudoternary phase diagram, The structure type, shape, particlediameter distribution and zeta potential of CFM-NE were investigated by staining method,transmission electron microscope and laser particle size analysator respectively. Its stabilitywas verified through temperature test, high speed centrifugal test and accelerated test.(2)Theanalytical method of CFM was established through ultraviolet-visible spectrophotometer.(3)We evaluated the safety through acute toxicity test, and according to the formula tocalculate the LD50and95%confidence limit.(4)Broth dilution method was used to determinethe MIC and MBC of cefixime nanoemulsion on Enteropathogenic E.coli, Staphylococcus,Salmonella, Streptococcus agalactiae and Acinetobacter.(5)The10day old chicks wereartificially infected with E. coli, dividing then into three groups including high, middle andlow dose of CFM-NE, CFM premix, control and healthy group, the efficiency and cure rateof infected chickens was investigated. Eveluating the CFM-NE curative effect of E. Coliinfected chikens.Result:(1)The mass fraction of the components in cefixime nanoemulsion were EL-4027.1%, cinnamaldehyde6.8%, cefixime2.0%, distilled water64.1%.The shape of cefiximenanoemulsion was spherical under TEM with the average diameter of12.1nm, polydispersityindex (PDI)0.141, zate potential10.6mV, the stability was good.(2)The linearity of CFMwas fine in the range of10～100μg·mL-1, the average recovery was (99.49±0.481)%, andrelative standard deviation(RSD) was0.483%, the six times repeated measurement of theaverage absorbance value was0.1587, RSD was0.325%. RSD of the with-in-day precisionand the day-to-day precision were0.345%and0.435%. All of the result showed that theanalytical method of ultraviolet spectrophotometry (UV) had high recovery rate, goodrepetitiveness and precision which could offer a good method for determining the content ofCFM.(3)The acute toxicity test showed that LD50was4116mg/kg and the confidence limitwas3641～4653mg/kg, it showed that CFM-NE belongs to low toxicity drugs with goodsafety.(4)The susceptibility test reveal that The MIC of cefixime nanoemulsion was1,4,4,2, 8μg/mL, MBC was2,8,8,4,16μg/mL, it was much better than CFM, amoxicillin tabletsand keflex capsule.(5)The cure rate of CFM-NE in high, middle and low dose group was90%,80%and66.7%respectively, and effective rate was93.3%,86.7%and73.3%83.3%respectively. The cure rate and effective rate of CFM premix was53.3%and63.3%, thecontrol group was26.7%. According to the statistical result, the average weight differencebetween the high and middle dose of CFM-NE was non-significant. They has extremelysignificant difference with control group,CFM premix group and low dose of CFM-NE(P<0.01) respectively.Conclusion: The prepared CFM-NE was transparent liqiudand has good stability, safetyand better therapeutic efficacy, it was obviously better than the effect of premix group for tre--ating clinical chicks infected with E. coli disease.