Study On The Long-acting Injection Of Eprinomectin

Eprinomectin（EPR）is currently the only antiparasitic drugs approved by the FDA for safe use in animals during pregnancy and lactation.Due to the frequent or improper use of common immediate release injections and pouring agents on the domestic market,it is easy to produce species resistance,and the pouring agent is easily affected by the external environment.This article combines EPR with an in-situ gel implanter delivery system to develop an EPR long-acting agent.The study and results are as follows:1.Pre-formulation studies:EPR equilibrium solubility and oil-water partition coefficients were determined.The results showed that EPR is easily soluble in methanol,glycerol formal（GF）and other organic reagents.It is very slightly soluble in water and has a strong lipophilicity.The HPLC chromatographic conditions for in vitro determination of EPR content were as follows:mobile phase:acetonitrile:methanol:water:trifluoroacetic acid=49:35:16:0.01,UV detection wavelength:245 nm,column temperature:35℃,flow rate:1 m L/min,injection volume:10μL,Column:C₁₈ODS 4.6×250 mm 5μm.The linear relationship was good in the range of0.05mg/m L～0.39mg/m L,and the regression equation（R²=0.9999）had good specificity.The precision and recovery rate met the methodological requirements.2.Prescription and in vitro release studies:Hydrophilic glycerol formal（GF）and lipophilic triacetin（GTA）were used as solvents,and PLGA was used as carrier to prepare long-acting EPR gel injection.The in vitro release method of EPR gel injection was determined,that was,the thermostatic oscillator speed was 100 rpm/min,tempreture was37°C,p H=7.4 PBS release medium was 50m L,take 4m L made up 4m L release medium,the cut-off molecular weight of dialysis bag was 3500.The effects of different PLGA molecular weights,block ratios and different solvent ratios on the release of EPR gel-injected liquids were investigated.The results showed that the release rate of EPR was faster when the molecular weight of PLGA with the same block ratio was smaller.The release rate of EPR was faster when the proportion of lactic acid of PLGA with a different block ratio of the same molecular weight was smaller.As the proportion of lipophilic solvent in the injection increases,the curing time is prolonged and the in vitro release of EPR is slowed.The scanning electron microcopy analysis showed that the pore size of EPR injections with the same block ratio and different molecular weights of PLGA was reduced with increasing PLGA molecular weight.With the proportion of lipophilic solvents in injections Increasing,the EPR gel injection solidified gradually into pieces,and the pore size gradually decreased.FT-IR showed that the EPR was successfully wrapped in a PLGA matrix after solidifying.DSC analysis showed that the EPR was presented in the PLGA matrix as an amorphous state.3.Pharmacokinetic of 5%EPR gel injection in rats:The concentration of EPR in plasma was determined by HPLC-fluorescence with a limit of quantification of 1.0 ng/m L.The drug release test in SD rats showed that there was a burst release in the first 4 days after administration,and then slowly released after 80 days.The plasma concentration was stable.The results of kinetic parameters showed that EPR was administered subcutaneously at a dose of 1 m L/50 Kg body weight into SD rats and the maximum plasma concentration was 71.96 ng/m L.The elimination half-life of EPR gel injection and the average residence time in the body were greatly prolonged,maintaining the effective plasma concentrations up to 80 days.Therefore,the prepared EPR gel injection had a significant long-term sustained-release effect.