Preparation And Partial Pharmacodynamic Studies Of Luliconazole Ethosomes

BackgroundLuliconazole is a kind of new-type antimycotic biosynthesis. It does this by inhibitingergosterol biosynthesis, play an anti-fungal effect. In recent years, because of itsexcellent antifungal activity,it has been attracted widespread attention in clinicalstudies.Ethosome is a new presence in drug delivery system in recent years, producedby adding liposome with ethanol, found to be much more efficient in delivering drugto the deep skin layers through stratum corneum with its physicochemical features.Therefore, Luliconazole ethosome can act as an optimal choice for expandingtransdermal antifungal drug in dermatological department. The purpose of thisresearch is to study the prescription ratio and physicochemical property ofLuliconazole ethosome,as well as to further analysis of the transdermal effect andantifungal activity of Luliconazole ethosome in vitro.Objective1、 Combination of luliconazole’s excellent antifungal activity and ethosome’sadvantages,this study is based on the preparation of Luliconazole ethosome, lookingforward to giving full scope to its partial pharmacology, offering a new perspectivefor choosing clinical antifungal drug in department of dermatologry.2、In way of screening on the preparation technologies and evaluation methods,thisstudy serves to bring ideas and experimental basis for research and development ofany other ethosomes.3、 In order to evaluate the potential pharmacological efficacy of Luliconazoleethosome, this study adopts the Franz diffusion cell to test the transdermal effect invitro and determine the antifungal activity by MIC. Accordingly, scientific data canbe collected for clinical research of luliconazole ethosome. 4、This is to evaluate the feasibility of the preparation of luliconazole ethosome, interms of evaluating the effectiveness of the preparation methods and testing methods,combined with studying the physicochemical property of the Luliconazole ethosomesoptimal prescription, thus offering experimental basis for extensive preparation ofclinical application.Methods1、 Preparation:Comparison of a thin-film hydration and injection technique inpreparation of ethosomes.2、Size:A laser dynamic Scattering instrument is used to analyze ethosome particlesize.3、 Entrapment Efficiency (EE%): Ultracentrifugation technique and dialysistechnique are applied to separate unentrapped drug. The drug content is quantified byHigh Performance Liquid Chromatography (HPLC)，4、HPLC: At room temperature, acetonitrile-0.1%ammonium dihydrogen phosphateas the mobile phase, taking the wavelength by UV spectrophotometer as the basis, andevaluating the precision and recovery of this methodology, etc.5、 Ethosome morphology: to observe and analyze by Transmission ElectronMicroscopy(TEM).6、 In vitro,transdermal experiments: Rat abdominal skin samples obtained afterdepilation, and is studied by Franz diffusion cell in the transdermal experiment.7、 In vitro,antifungal activity of luliconazole ethosome: MIC is determined themicro-broth dilution assay.Result 1、During Luliconazole ethosome preparation,we found that the thin-film hydrationtechnique is more suitable for the preparation of Luliconazole ethosome comparedwith injection technique in the aspects of the entrapment efficiency and the size of theethosome. And ultracentrifugation technique is simpler and faster than dialysistechnique regarding the evaluation preparation techniques.2、It is discovered in this study that the concentration of the ethanol and lecithin takepositive effects on the entrapment efficiency while the concentration of ethanol isnegative to the size of the ethosome which grows with the content of lecithin. Whensize and entrapment efficiency are adopted for the optimal prescription, the ethosomepreparation with5%(w/v) lecithin，45%(v/v) ethanol under ultrasonic time in8min,the particle size of luliconazole ethosome is small, scattered evenly with entrapmentefficiency as high as70%.3、Luliconazole ethosome and various luliconazole non-ethosome formulations arecarried out by Franz diffusion cell experiments in vitro transdermal experiment. Forthe penetration rate of various luliconazole formulations, the result shows:ethosome>ointment>liposome> hydroalcoholic solution. Ethosome is better intransdermal amount in24hours than the other types, and in the retention of drug after48hours, much better than liposome and hydroalcoholic solution,and is a match forointment.4、 From the fungistat experiments of different formulations of luliconazole invitro,we conclude that the fungistat effect of the luliconazole ethosome is better thanliposome and hydroalcoholic solution.The sensitive degree of luliconazole ethosometo trichophytosis is higher than the sensitive degree to candidiasis.Conclusion1、The ethosome prepared by the thin-film hydration technique bears advantages ofhigh entrapment efficiency and good permeation efficacy. 2、The optimal prescription indicates that the luliconazole ethosome preparation iswith5%(w/v) lecithin、45%(v/v) ethanol, and its particle size is small, with highentrapment efficiency,and it has the advantantages of little stimulativeness and goodstability.3、Ethosome has better permeation efficacy in skin than liposome, hydroalcoholicsolution and ointment to be marketed soon.4、In vitro, the antifungal function of luliconazole ethosome is better than liposomeand hydroalcoholic solution.