Research And Development Of The Trans-cinnamic Acid Microemulsion Gel And The In Vitro Absorption

Objective:The trans-cinnamic acid has a good anti-inflammatory effect,and is difficult to dissolve in water at room temperature.The oral bioavailability is not high,and the microemulsion is thermodynamically stable.It can not only improve the absorption and utilization of drugs,but also avoid adverse reactions caused by drugs.In this study,the preparation of cinnamic acid microemulsion gel was studied.First,cinnamic acid microemulsion was prepared and its related characterization was measured and investigated.Then,the transdermal permeation accumulation of cinnamic acid microemulsion and its microemulsion gel preparation and the residual amount of drug in the skin after transdermal were measured and calculated.To evaluate the transdermal effect of cinnamic acid and provide some reference value for the anti-inflammatory application of trans-cinnamic acid in the future.Methods:Firstly,the solubility of cinnamic acid in oil phase,surfactant and co-surfactant was determined and screened.Then,microemulsion was made by water drop method,and pseudo-ternary phase diagram was drawn to determine the proportion.The maximum drug loading was determined and the optimal microemulsion formula was selected to determine the drug loading ratio.Then the particle size,Zeta potential,PDI,electrical conductivity and so on were measured,and its stability was investigated.Then,the oil phase was used as a control for in vitro transdermal experiment for 24h,and the optimal microemulsion was selected.The morphology,size and distribution of the microemulsion were detected by transmission electron microscopy.Carbomer940 in different proportions was used to make microemulsion gel preparation,and its p H was determined.The best microemulsion gel formulation was selected by in vitro transdermal experiment again.Results:Through solubility data size filter oil phase(oleoyl polyoxyl-6glycerides,oleic acid),the surfactant(PEG 400,tween 20,Labrasol,Kolliphor EL,tween 80),and helps the surfactant(absolute ethanol and isopropanol),after through the pseudo ternary phase diagram and the largest drug loadings of the investigation,and determine the drug loadings was 1%,and the preparation of four groups of blank and drug loading microemulsions.Through the investigation of microemulsion characterization,it was determined that ME3 was the optimal formula,which consisted of 65%water,35%oil phase(oleoyl polyoxyl-6 glycerides)and mixed surfactant(Labrasol:absolute ethanol=2:1),and the ratio of the latter two was 3:7.The particle size is 71.4?1.7 nm,the PDI is 0.331?0.003,zeta potential is-38.32?0.13 m V,its stability is good,the trend of electrical conductivity in a rising state,good distribution under transmission electron microscope,conform to the size form before judgment.In the transdermal experiment,the permeation accumulation of ME3(1%drug)was the highest,which was 830.7μg/cm~2,and the permeation accumulation of GEL3containing 2.5%carbomer 940 was the highest,which was 676.7μg/cm~2,and the residual amount in skin was 20.80μg/cm~2.It is considered as the optimal formulation.Conclusion:The experimental results show that the developed cinnamic acid microemulsion and its gel preparation meet the expected requirements,and the preparation process is simple,good stability,and can be well wrapped into the system,which provides a certain reference for the anti-inflammatory application of cinnamic acid in the future.