Preparation Of Diclazuril Nanoemulsion And Its Efficacy Against E.tenella In Chicken

Diclazuril was one of the most useful anticoccidiosis drugs in clinical application.It was limited because of its unsolution, short half-life, and low bioavailability. Microemulsion was a novel drug delivery system, which was a clear isotropic mixture consisting of oil,water,surfactant and co-surfactant. The characteristics of nanoemulsion were low viscous, stable in thermodynamics and kinetics. Its diameter was less than 100nm and easy to prepare.Its formation was spontaneous and no energy was required. It can be used either as a carrier of hydrophilic or lipophilic drugs. So nanoemulsion can be used to enhance the absorption of poor solubility drugs, improve the bioavailability of drug , as well as possess the characteristics of targeting and sustained release. To improve the treatment efficacy, we drawed nanoemulsion phase diagram, studied the characteristics and preparation craft of diclazuril nanoemulsion.and also detected the efficacy of diclazuril nanoemulsion against coccidiosis.In the preparation and characteristics of nanoemulsion, we officialy used non-ionic surfactant, beacause the ionic surfactants are generally too toxic to be used for this application. Tween-80and Span-80 as mixture surfactant, several alcohols with low molecular as co-surfactant, IPM oil is used as oil phase and distilled water as the aqueous phase. Ternary phase diagrams are developed using water titration method, the mixtures of oil and surfactant/co-surfactant at certain weigh ratios are diluted by water in a drop-wise manner. Nanoemulsion is prepared by mixing the above components in proper ratio. The results showed that nanoemulsion was obtained when Tween-80 and Span-80 as a mixture surfactant(Tween-80 : Span-80=5:1), IPM oil as oil phase and the ratio with mixture surfactant is 6:4.The area of existence of nanoemulsion regions is maximal at this ratio. The physical stability of the nanoemulsion was assessed by centrifugation at 4000rpm for 30min, storage at 30±2℃and relative humidity 60±5% for six months, No phase separation was observed ,so, we can found that the nanoemulsion has a good stability.Based on the optimal prescription and preparation process of nanoemulsion, we prepared diclazuril nanoemulsion, the content of drug loading were determined by Ultraviolet Spectrophotometer, the diameter of diclazuril nanoemulsion was determined by Transmission Electron microscope and size distribution instrument.The results showed that diclazuril nanoemulsion was spherical in shape,its average diameter was 6.92nm. The absorbency and content of diclazuril was linearly dependent in 5～25μg/mL, R2=0.9989. The recovery was between95%～100%, and the RSD of precision with-day and that between-day were all smaller than one. So, the diclazuril nanoemulsion prepared was stable and the means of UV spectrophotometry established was equal to analyse the content of diclazuril. We detected its term of validity was 25 months.We detected the toxicity of diclazuril nanoemulsion, The result showed that the acute toxicity LD₅₀ of diclazuril nanoemulsion was more than 5000mg/kg.showed that the diclazuril nanoemulsion infactlly has no toxic.We studied the efficacy of the diclazuril nanoemulsion against coccidiosis in vivo.the results showed that diclazuril nanoemulsion had better activities on coccidiosis, the ACI is 192.5.it is a high efficacy durg against coccidiosis. We also done some clinical exprement, in the prevention and treament experiment ,we contrast the dies rate and the cure rate between diclazuril nanoemulsion group and diclazuril water-soluble fluid group, p<0.05, the result showed that the diclazuril nanoemulsion can depress the chickens dies rate and enhance the cure rate.so, diclazuril nanoemulsion better than diclazuril water-soluble fluid.