Study On Preparation And Pharmacokinetics Of Ivermectin Submicron Emulsions

Ivermectin (IVM) is a novel antibiotics insecticide which has a wide antimicrobial spectrum. It is lower toxicity and more effciency. Currently, Plasma concentration changes largely of normal IVM formulations which leading to a lower safety and efficacy in veterinary clinical applications.Submicron emulsion as a noval formation of drug delivery sysytem, can protect drug, improve drug stability, prolong interaction time and reduce few side-effects. Intravenous injection is a way which can prevent the abuse of veterinary drugs, so we consider made IVM into submicron emulsion which can povide fundmental work for a new dosage of IVM.Preformulation research of IVM was investigated to develop HPLC method for IVM content determination. IVM submicron emulsion was prepared by high pressure homogenization technique. In order to choose the best formulation and preparation process, the droplet size, PDI, the value of (?) potential and the drug concentration of IVM submicron emulsion were investigated.The stability of IVM submicron emulsion was also investigated. It included the impact of sterilization and the main emulsifier on its general physico-chemical properties of IVM submicron emulsion. IVM submicron emulsion was stable at4℃and25℃,and it should not be kept at a condition of high temperature and light.Quality standards were preliminary reseached. The properties include particle size, Zeta potential, pH value, content of IVM and Osmotic pressure were investigated. Besides, free fatty acid, peroxide value and the related substances of the emulsion were examined. The HPLC method was suitable for IVM content determination.To study its pharmacokinetic characteristics, a HPLC-UV method was validated to quantitatively determine IVM concentration in rat plasma. The pharmacokinetic study was conducted in rats by intravenous (i.v.1mg/kg). The concentration-time profiles of IVM submicron emulsion and general injection in plasma fitted a three-compartment model. IVM submicron emulsion is a good choice for intravenously administrating poorly soluble IVM. The T1/2Pi of general injection and IVM submicron emulsion were0.03±0.013h and0.031±0.002h. The T1/2α of general injection and IVM submicron emulsion were0.582±0.050h and0.827±0.150h. The t1/2β of general injection and IVM submicron emulsion were14.082±1.703h and72.474±26.82h. AUC of general injection and IVM submicron emulsion were8.115±0.218(mg/L)*h and50.353±13.29(mg/L)*h. IN CONCLUSION, IVM submicron emulsion can significantly prolong half-life of IVM and improve the bioavailability.