Preparation And In Vitro Transdermal Absorption Of Enoxacin Microemulsion

Objective:Enoxacin(ENX)is the third generation of quinolone antibiotics.It has rapid bactericidal effect on Gram-negative bacteria and Gram-positive bacteria,and there is no obvious cross resistance with other antibiotics.It mainly acts on topoisomerase IV and DNA helicase to inhibit the synthesis and replication of bacterial DNA,resulting in the death of bacteria.It is mainly used in the treatment of respiratory tract infection,gastrointestinal tract infection,urogenital system infection and soft tissue infection caused by gram-negative bacteria and Gram-positive bacteria.Currently,commercial formulations include tablets,creams,capsules and eye drops.However,the poor permeability and solubility of enoxacin make its antibacterial activity difficult to achieve the best effect,and its oral administration will lead to serious gastrointestinal reactions.Therefore,it is necessary to prepare a new formulation of enoxacin to improve its solubility,permeability and avoid gastrointestinal adverse reactions.Transdermal drug delivery system(TDDS)is a common way of drug delivery.In the process of percutaneous drug delivery,the drug passes through the skin and capillaries at a corresponding rate,and then is absorbed by the human body,which can be used in the process of systemic and local treatment.Compared with other drugs,transdermal drug delivery can effectively increase the action time of the drug itself and reduce the adverse reactions of gastrointestinal tract.From the current development situation,it is a key topic in modern medical research.However,in the actual application process,due to the direct influence of skin barrier and drug properties,there are some deficiencies in the overall penetration of the drug,which will inevitably have a certain impact on the drug effect.Therefore,in the process of practical application,how to effectively improve the penetration rate of the drug itself and ensure that the efficacy can be better played is the focus of the subsequent optimization of the transdermal drug delivery system.Microemulsion is a transparent or translucent thermodynamic and stable oil-water mixing system formed by mixing water phase,oil phase,surfactant and cosurfactant in proper proportion.Microemulsion has obvious solubilizing ability to drugs,which can increase the penetration rate,improve stability,prolong the time of action,and make the preparation process simple and low cost.At present,the application of microemulsion in the transdermal drug delivery system has attracted much attention in the medical field.A lot of reports have been reported on the application of microemulsion in NSAIDs,antineoplastic drugs,hypoglycemic drugs and so on.Microemulsion is the key carrier of transdermal drug delivery,and it has a positive effect in the process of transdermal delivery.Therefore,this experiment is devoted to the preparation of enoxacin microemulsion.The physicochemical properties of the microemulsion were determined and the transdermal effect of enoxacin microemulsion was evaluated in vitro.Methods:Firstly,the materials of microemulsion components were screened.According to the characteristics of oil phase,surfactant and cosurfactant,interaction and the influence of the solubility of enoxacin,the suitable components were selected.The water drop method was used to analyze the oil phase and surfactant in different proportions,and the corresponding pseudo ternary phase diagram was drawn according to the titration results.The proportion of oil phase,surfactant and cosurfactant was determined by pseudo ternary phase diagram,and the alternative formulation was selected.The physical and chemical properties of the microemulsion formulation were tested,including pH value,transmittance,conductivity,particle size and polydispersity coefficient.In addition,24 h skin penetration test was carried out for different proportion of microemulsion formulation,and the best microemulsion formulation was selected with the largest penetration of microemulsion.Results:The proportion of mixed surfactants was determined by drawing pseudo three phase diagram,and 3 microemulsion formulations were selected to test the physical and chemical properties.The oil phase was oleic acid polyethylene glycol glyceride,the surfactant was Tween-80,the cosurfactant was anhydrous ethanol and isopropanol,the water phase was distilled water,and the ratio of mixed surfactant was 1:1 and 2:1.By studying the physicochemical properties and drug loading ability of the alternative microemulsion formula,the particle size of the drug containing microemulsion is between 100.6-105.4 nm,and the Zeta potential is between-38.54 mV and-38.30 mV,and pH is between 5.54-5.85.The transdermal test results of 24 h showed that the penetration rate of enoxacin in 3 microemulsion formulations was much greater than that in the oil phase.Microemulsion F3 was the best.Conclusion:The results showed that the microemulsion formulation was suitable for transdermal delivery of enoxacin,and the formulation was simple and stable,which significantly improved the percutaneous penetration rate and cumulative skin penetration of enoxacin,providing a new idea for the study of enoxacin after transdermal delivery.