Preparation,Quality Evaluation And In Vitro Transdermal Study Of Neohesperidin Microemulsion-based Gel

Objective:The aim of this study is to develop a novel dosage form for transdermal drug delivery of neohesperidin,determine its physical and chemical properties and perform in vitro transdermal experiments on neohesperidin microemulsions and microemulsion-based gels to evaluate the effect of transdermal penetration with different microemulsion formulations and the effect of different gel quality on transdermal effects after the optimal microemulsion was made into gels.The optimal formulation was selected to improve the solubility and bioavailability of neohesperidin and provide a basic theoretical basis for clinical studies.Methods:The solubility of neohesperidin in different oil phase,surfactant and cosurfactant was screened.The oil phase,surfactant and cosurfactant with high solubility were determined.The microemulsion was titrated by water drop method.Different proportions of oil phase and surfactant of different proportions were mixed with cosurfactant(K_m).Titration was carried out by adding distilled water drop by drop to determine the addition amount of oil phase,K_m and distilled water.The mass ratio of oil,surfactant,cosurfactant and water were determined by constructing pseudo-ternary phase diagram and selecting formula composition of microemulsion with large microemulsion area.The stability,light transmittance,p H,conductivity,particle size,polydispersity,Zeta potential,differential scanning calorimetry,morphological observation and fourier transform infrared spectroscopy of the microemulsion were determined.In vitro transdermal experiments were performed to compare the transdermal permeability of drugs in different microemulsion formulations and in a single solvent,polyethylene glycol glyceride.Then 1.0%,1.5%and 2.0%(w/w)cabomer 940 were added into the optimal permeability microemulsion formula to compare the percutaneous permeability of the three microemulsion-based gels.Results:According to the solubility and the size of the pseudo-ternary phase diagram of the microemulsion area,four microemulsion formulations were formed by different ratios,with Labrafil M 1944 CS as the oil phase,Triton X-100 and Tween 20 as the surfactant,and Transcutol P and 1,2-propanediol as the cosurfactant.The particle size of the blank microemulsion was 18.77-30.90 nm,the particle size of the drug-containing microemulsion was 24.50-50.50 nm,and the potential was between-38.45 and-38.30 m V.After 24 h,the cumulative penetration of the drug in four microemulsions(ME1,ME2,ME3,and ME4)and Labrafil M 1944 CS was 1.16±0.10,1.57±0.14,0.88±0.17,2.13±0.33,and 0.37±0.02 mg/cm~2,respectively.The percutaneous penetration of the three microemulsion-based gels was 0.65±0.06,0.96±0.02 and 1.36±0.19 mg/cm~2,respectively.Conclusion:The optimal formulation of microemulsion ME4 was 15%oil phase(Labrafil M 1944 CS),35%K_m(mixed with Tween 20 and Transcutol P in a ratio of 2:1)and 50%water,and the percutaneous permeability of microemulsion was significantly different from that of other groups(P<0.05).When 1.0%,1.5%and 2.0%carbomer 940 were added into the optimal microemulsion formulation,the transdermal ability of microemulsion-based gel increased with the increase of the amount of carbomer 940.