Preparation And Pharmacodynamic Evalvation Of Lidocaine Microemulsion Gels

Objective:To investigate the transdermal preparation method of medicine preparation of lidocaine microemulsion gel, after in vitro evaluation, the analgesic effect of microemulsion gel preparation was assessed by the preliminary Pharmacodynamics Study, further, its skin irritation was detected, with a view to lidocaine development become a local new percutaneous medicine lay the experimental foundation.Methods:1.Analysis method of lidocaine HPLC chromatography was established, and the physical and chemical properties of lidocaine was studied.2. Using ethyl oleate as the oil phase, Twain -80 as surfactant, ethanol as co surfactant, by drawing the pseudo-ternary phase diagram to determine the optimal Km value, titration method water preparation of lidocaine microemulsion. Through the percutaneous penetration experiment, determine the microemulsion drug loading, and the optimum microemulsion formulation for the in vitro release experiment. The morphological observation by transmission electron microscope and laser particle size analyzer, particle size and distribution, and the stability of the microemulsion was investigated.3. Through in vitro transdermal experiments, skeleton and the dosage of lidocaine microemulsion gel were screened, then prepared by direct swelling method, and futher carried out the optimum microemulsion gel prescription study and preliminary stability investigation of the properties of physical and chemical test.4. Using the classical analgesic experiments, inspects the analgesic effect of lidocaine microemulsion gel, and further study on its skin irritation.Result:1. The establishment of a high sensitivity, specificity, reproducibility and accuracy were good, and the operation of the HPLC method is simple, for the determination of lidocaine. Physicochemical properties of lidocaine showed that lidocaine is the preparation of transdermal drug delivery formulations suitable.2. The optimum formulation of lidocaine microemulsion:lidocaine content is 2%, ethyl oleate was 4%, Twain-80 was 15%, for 9% of anhydrous ethanol, deionized water is 70%. In vitro optimal formulation of lidocaine microemulsion releasing performance is good, the size of microemulsion are about 40nm, transmission electron microscopy showed spherical droplets, stability study showed the microemulsion preparation was stable.3. Through screening to determine the gel matrix for Carbopol 940, the optimal prescription of lidocaine microemulsion gel:Carbopol 940 was 0.5%, the content of lidocaine 2%, ethyl oleate was 4%, Twain-80 was 15%, for 9% of anhydrous ethanol, deionized water is 69.5%. Optimal microemulsion gel formulation of preparations in vitro release behavior near zero order release, physicochemical properties and stability of the preliminary investigation results show that the physical and chemical properties and stability of the preparation were good.4. The analgesic experiments show that, in low, high dose, the microemulsion gel can dose dependently increased the pain threshold of mice, and in the same dosage, microemulsion gel, high doses of 45min and 60min in the blank control group, with 2% lidocaine gel group, solution of 2% lidocaine group were statistically significant (P<0.05), these results suggest that the analgesic effect of microemulsion gel, high dose than gel good. The skin irritation test results show that, the high dose of microemulsion with mild irritation to normal intact skin, microemulsion gel high dose to normal intact skin without irritation, but microemulsion and microemulsion gel with high dose to the broken skin with mild stimulation, suggesting that lidocaine microemulsion gel has good safety.Conclution:Lidocaine microemulsion gel has the advantages of simple preparation process, easy coating, small particle size and uniform distribution of local anesthesia, showed better analgesic effect and good safety, developing it as a local transdermal drug delivery system has certain value in clinical application.