The Design Of Long-acting Ivermectin With Trans-dermal Agent And The Pharmacokinetics

As one of the most widely used veterinary parasite drug resistance currently in the word,ivermectin is often used in clinical prevention and treatment of animals such as cattle,sheep with nematodes,ticks,mites and other external parasites.It has been made into a variety of dosage forms such as an oral agent,injection,capsule,transdermal agent,ointment,liniment,long-term controlled release and relievers now.It's severely restricts the parasitic disease prevention and control on the market at present,the transdermal agent,oral drugs have short effective time and should to be used repeated;the injectable drugs didn't suitable for grazing areas and large farms because it takes work too much.Our aim is to solve the problem of farms to medicines laborious and develop the long-acting transdermal agent of ivermectin which is long effective time,good stability,high efficiency.1.We have preparation three concentrations 0.5%,1.0%,1.5% at the long-acting transdermal agent of ivermectin by select appropriate proportion of cosolvent,penetrating agent,and a long-term agent according to the physical and chemical properties of ivermectin.To gain the best long-acting transdermal agent of ivermectin by observing the stability of the drug,high temperature test,freeze stability test and drug screening for determination of the degree of precipitation test.The content of ivermectin in preparation HPLC-UV is accurate and reliable by drawing standard curve,precision and recovery rate,and they all conformed to the requirements of the country?2010 Edition of The Chinese Veterinary Drug Standard?.2.For the pharmacokinetic experiment: three groups of the long-acting transdermal agent of ivermectin in rabbit which is the same concentration of different volume of and optimization the method of ivermectin in content determination in rabbit plasma.The method conforms to the requirements of analysis in biological samples by drawing standard curve,precision and recovery,the lod and loq.The drug can be quickly absorbed through the skin into the bloodstream,give play to effect through ivermectin in plasma concentration change with time of the data,which is single homogeneous spraying outside of rabbit ears.The concentrations of long-acting transdermal agent of Ivermectin0.5%,1.0% and 1.5% turned down to 1,2,3 groups,and through the PK Solver pharmacokinetic for data analysis,the t1/2ka of groups 1,2,3 respectively: 0.52 d,0.35 d,0.75 d;the T_max : 1.47 d,1.13 d,1.23 d;the C_max : 91.09 ng·m L^-1,37.61ng·m L^-1,69.53 ng·m L^-1;the t_1/2ke : 3.55 d,4.95 d,4.61 d;the MRT : 9.995 d,11.902 d,6.995 d;the AUC : 7578.33,5530.75,542.20 ng·d·m L^-1.Three groups of drugs in rabbit plasma which conform to absorb one room open model,and group 2 absorption half-life and peak in the shortest time and the average residence time is the longest and best effect.In conclusion,the long-acting transdermal agent of Ivermectin has significant long-term effects maintain and concentration time 35 d which was in rabbit blood drug concentration changes smoothly.3.For the pharmacokinetic experiment: three groups of the long-acting transdermal agent of ivermectin and the control group common injection in rabbit which is the same volume of different concentrations.The methods were same as part 2.Through the PK Solver pharmacokinetic for data analysis,the t1/2ka of groups 1,2,3,4 respectively: 0.81 d,0.52 d,1.02 d,0.12 d;the T_max : 1.55 d,0.97 d,1.62 d,0.42 d;the C_max : 47.36 ng·m L^-1,72.02 ng·m L^-1,115.3 ng·m L^-1,99.53 ng·m L^-1;the t_1/2ke : 3.61 d,5.92 d,5.59 d,1.79 d;the MRT : 5.27 d,7.37 d,5.13 d,2.16d;the AUC : 1488.70,3081.98,3161.2,480.0 ng·d·m L^-1.It shows that four groups of drugs in rabbit plasma which conform to absorb one room open model,the group common injection effective drug concentration in the body for 9 d and concentration drops rapidly rising first and then in a straight line.The long-acting transdermal agent of ivermectin release for a long time and the blood drug concentration in rabbit body was slowly rising trend and changes smoothly which is concentration time for 35 d,the concentrations 1% of the agent is the longest and best.To sum up,the long-acting transdermal agent of Ivermectin formula conforms to the requirement of Chinese Veterinary Drug Standard,through the determination of rabbit in pharmacokinetics and drug curve and pharmacokinetic parameters determination,the preparations has long-lasting effect,and the effective drug concentration time up to 35 d.The optimal concentration of is 1.0% through comparison three concentrations 0.5%,1.0%,1.5% at the long-acting transdermal agent of ivermectin by observing the stability of the drug,high temperature test,freeze stability test,the drug screening for determination of the degree of precipitation test and the experiment of pharmacokinetics.