Study On The Drug Delivery System Of Fusidic Acid Loaded Microemulsion

The content of this paper is to prepare a novel fusidic acid(FA)loaded microemulsion(ME)delivery system,to study the physicochemical properties and stability,to investigate the in vitro release and penetration amount,and to evaluate the antimicrobial efficacy and skin safety.The results demonstrated that FA loaded ME,as a topical agent was applied to treat bacterial-induced skin infections which was very effective and safe.Specific work has the following several aspects.1.The solubility study of FA was to obtain the appropriate components of ME with a high FA loading capacity in various surfactants,co-surfactants and oils.Microemulsions were developed via pseudo-ternary phase diagrams combined with physicochemical characteristics.The characteristics of microemulsion and the in vitro release were utilized to screen and optimize the ME formulation.Following the optimization,the optimized formulation(M4)was comprised of 25.5 % the mixed surfactants,the mixed oils 7.5 % and 67 % water,respectively.The morphological characteristics of M4 were observed by TEM,which appeared non-aggregated globules.The mean droplet size of M4 was 28.33 nm.No significant change of physicochemical properties was observed after 3 months.These reveal high stability of M4 over time.2.The spray of ME was evaluated according to its evaporation time,spray pattern,spray angle and ex-in vivo physical parameters.M4 fulfilled the desired criteria of the film formation and integrity of the skin as it exhibited no crack or rubbed off during the wearing period,which indicated adequate strength and flexibility of film.None of the formulations resulted in irritation,rashes and itching in any of the volunteers.The results showed that M4 has no skin irritation.3.The in vitro release behavior of microemulsion was conducted by bulkequilibrium reverse dialysis bag technique.The result showed that the amount release of FA in the first 2 h reached 80 %.The drug permeation percentage in phosphate buffer solution(pH=7.4)with 0.5% sodium dodecyl sulfate(SDS)showed that in the first 24 h,M4 and M0 were 82.35% and 58.39%,respectively,which was significantly different.The result demonstrated that ME had the effect of enhancing the drug transport.4.The inhibitory effect of M4,FA-DMSO and M9 against the three bacterial strains(S.aureus,S.epidermidis,P.acnes)was also evaluated by bacterial inhibition zone,minimum inhibitory concentration(MIC)assays and antibacterial ability in a specific time.The results demonstrated that no-loaded drug micromulsion(M9)has the antimicrobial effect.M4 possessed a superior antimicrobial effect against the three tested strains,and ME enhanced the antimicrobial effect and improved the pharmacodynamic potential for fusidic acid.5.The partial animal experiments on skin irritation reaction have been done.The results indicated that M4 did not induce the skin irritation,so the M4 is a newly spray with better security.The innovation of this paper was described as follows:1)The purpose of present study was to prepare and optimize a novel spray-like FA loaded ME,and to improve the semisolid dosage forms disadvantages.Spray dosage form improved patient compliance and acceptance via targeting the drug directly to the affected area of the skin,which reduced the cross-infection and was convenient for patients.Moreover,ME enhanced the solubility of FA and improved the stability.It exhibited powerful penetration by overcoming the skin barrier of the stratum corneum.2)Tocopherol Polyethylene Glycol 1000 Succinate(TPGS)has been approved as a safe surfactant by the FDA.TPGS promoted the local retention of the drug in the skin,resulting in improved therapeutic efficacy and minimalizing systemic side effects.As a derivative of vitamin E,TPGS released free vitamin E,which treated dermatologic disorders by promoting collagen synthesis to stabilize the skin barrier.Moreover,TPGS acted as a plasticizer to promote the formation of a stretchable and flexible film in the spray system compared with other surfactants.It simplified the composition of the ME drug delivery system.