Study On Preparation And Pharmacokinetics Of IVM Pour-on And Ceftiofur Hydrochloride Suspension

Ivermectin(IVM)is a broad-spectrum antiparasitic drug which can kill a variety of parasites such as nematodes and mites.IVM has the advantages of low toxicity,high efficiency and low residue.Pour-on is a transdermal preparation that overcomes some disadvantages of other dosage forms.In this study,in order to develop 0.5% IVM pour-on,the optimal prescription was screened through in vitro transdermal experiment.And its stability and pharmacokinetic properties in rat were evaluated.Determination of IVM in vitro was established by HPLC.The mobile phase of HPLC was a mixture of acetonitrile,methanol and water(55:37:8,v/v/v).With the concentration of IVM as the horizontal coordinates and the peak area(A)as the vertical coordinates,the linear regression was performed within the range of 1~100 ?g/m L and the regression equation was A = 0.4954 C + 0.0728(R2 = 0.9999).The method could be used for the determination and stability study of IVM pour-on because of the advantages of strong specificity,high accuracy and repeatability.The solvents of IVM pour-on were isopropyl alcohol,isopropyl myristate and liquid paraffin.Nine formulations were designed by varying the amount of isopropyl myristate and liquid paraffin.In vitro transdermal experiments were performed by percutaneous diffusion permeameter.The cumulative permeation quantity of each formulation was determined by HPLC.The optimal formulation was selected according to the cumulative permeation quantity.The stability of IVM pour-on was estimated by high temperature test,illumination test and accelerated test.Under the conditions of high temperature test at 60 ? and illumination test,the appearance and content of IVM pour-on were changed.Therefore,the preparation should be stored to avoid high temperature and strong light.The pharmacokinetics of IVM pour-on was conducted in rats.Plasma concentrations of IVM in rat were determined by HPLC.The pharmacokinetic characteristics of IVM injection and IVM pour-on in rat were analyzed.The t1/2z of IVM injection and pour-on were 246.51±63.56 h and 862.36±401.82 h.The AUC0-t were 14774.61±3778.38 ?g/L*h and 12503.88±4181.19 ?g/L*h.The AUC0-? were 22455.84±8975.97 ?g/L*h and 21050.37±9613.34 ?g/L*h.The Tmax were 12.00±0.00 h and 21.00±6.00 h.The Cmax were 56.65±18.73?g/L and 42.63±3.28 ?g/L.The results showed that IVM pour-on could prolong the half-life and improve the bioavailability of the drug.Ceftiofur hydrochloride is a cephalosporin antibiotic,which is a special antimicrobial for animals.It has the advantages of wide antibacterial spectrum,good antibacterial efficacy,high curative rate and few side effect.Ceftiofur hydrochloride suspension was developed.The quality of the preparation was evaluated and its pharmacokinetics in rat was analyzed.Determination of ceftiofur hydrochloride in vitro was established by UV spectrophotometry.The UV absorption scanning was performed in the wavelength range of 200~400 nm,and ultimately the maximum absorption of ceftiofur hydrochloride was determined at 289 nm.The absorbance of ceftiofur hydrochloride solutions in different concentrations was determined at the wavelength of 289 nm.The linear regression was performed within the range of 1~15 ?g/m L and the regression equation was A = 0.0621 C + 0.0108(R2 = 0.9997).Specificity,precision and recovery rate for the method were in accordance with methodological requirement,so the method could be used for the determination of ceftiofur hydrochloride.The prescription of ceftiofur hydrochloride suspension was screened by orthogonal method.We chose soybean oil as the dispersion medium for ceftiofur hydrochloride suspension and ascertained factors and levels.The formulations of L9(34)were designed according to orthogonal experiment of three factors and three levels.The optimal prescription was obtained by analyzing the sedimentation volume ratio and viscosity of each formulation.We investigated dispersive test,particle size distribution and needle of the selected prescription and concluded that the quality index of the preparation met the requirements.Compared with commercial ceftiofur hydrochloride injection,the pharmacokinetics of ceftiofur hydrochloride suspension was evaluated.The plasma samples were collected after rats were intramuscularly injected at a dose of 50 mg/kg.The plasma concentration of ceftiofur hydrochloride in rats was established by HPLC.Finally,the pharmacokinetic characteristics of ceftiofur hydrochloride in rats were discussed.The AUC0-t of ceftiofur hydrochloride suspension and ceftiofur hydrochloride injection were 109.83±26.08 mg/L*h and 75.18±22.89 mg/L*h.The AUC0-? were 156.83±71.86 mg/L*h and 86.12±25.77 mg/L*h.The t1/2z were 7.55±2.56 h and 5.94±1.89 h.The Tmax were 0.46±0.10 h and 0.25±0.00 h.The Cmax were 55.72±6.71mg/L and 55.23±5.27 mg/L.