Preliminary Studying Of Preparation Of In Situ Gel Implants Containing Ivermectin And Drug Release Profile In Vivo In Rabbit

As a new broad spectrum antiparasite macrolides drug,Ivermectin has been to obtain abroad application among the clinic veterinary medicine which has not only high performance effect against mites but also has stranger result against the nematode and insects.To face to the 1% Ivermectin injection at the markert,we investigate the 3%injectable in situ gel implants containing Ivermectin.firstly,preparated the injectable in situ gel implants containing Ivermectin,and it has the good gel and syringeability.The burst effect is very big at BA or NMP solution and low concentration PLA for injectable in situ gel implants containing Ivermectin,and the drug burst effect release concentration are approximation,there is a maximum point at PLA concentration effecting the burst effect,the time of burst effect move to the fourth day from the frist day.These are not the good choise for Ivermectin,the solution is very important for the burst effect,the burst effect is very small with liposolubility solution,but preparation'drug release is also slow relatively.At the high concentration PLA and different dissolubility solution,10%PLA and hydropHilic NMP could be choose as the primary parameter for injectable in situ gel implants containing Ivermectin.Next,we have screened the concentration and solution parameters using the orthogonal design.General result, the effect is the best with DMF and 12%PLA preparation.Accumulative drug release achieve the 94%at 50 day end,and the burst effect is only 27%at the first day,the gel is good,these result are consistent with ours primary design.Verification trials reveal the good reproducibility.We have experiment the rabbits in vitro,12 rabbits are randomly separated to two groups,one are injected 200ug·kg^-1 with 1%Ivermectin injection and other are injected 630ug·kg^-1 with 3% injectable in situ gel implant containing Ivermectin.Blood plasma are extracted with acetic ether and acetonitrile,the extracted liquid are derivatizationed with N-methylimidazole and trifluoroacetic anhydride,the derivatizationed samples are analyzed by BR-HPLC with fuorescent detector,result data are treatmented with das2.0 pHarmacokinetics software,To the 3%in situ gel implants containing Ivermectin,the max blood drug concentration present at the 2nd day,and the blood drug concentration is low to 60ng·mL^-1,To the 1%Ivermectin injection,the max blood drug concentration present also at the 2st day,but the blood drug concentration is near to 80ng·mL^-1. PHarmacokinetics parameters reveal the two preparations consistent both with two-compartment model.The t_1/2 is 9.99 day for 1%preparation,20.52 day for 3%gel preparation.The MRT is 9.35 day for 1%preparation and 10.19day for 3%gel preparation.In situ gel implants reveal more long t_1/2 and MRT compare with conventional injection for Ivermectin.The MRT of in situ gel implants containing Ivermectin is near with foreign commercial drug' MRT,but in situ gel implant may have more biocompatibility.All indicate that 3%in situ gel implants containing Ivermectin deserve more attention.