Preparation Of Esculetin Microemulsion And Determination Of Physicochemical Property

Objective: Objective: Esculetin(ES)is one of the effective components of the cortex lucidae.However,due to its low water solubility and poor bioavailability,there is no suitable formulation for Esculetin at present.This study intends to develop a new microemulsion prescriptionfor the oral administration of Esculetin and improve the solubility and bioavailability of Esculetin.The physical characteristics and irritation of intestinal mucosa were also investigated.Methods: Firstly,the materials of microemulsion were screened,and the appropriate components were selected through the properties of oil,surfactant and cosurfactant,and the solubility of Esculetin.The ratio of fixed surfactant and cosurfactant was screened by pseudo ternary phase diagram,and the alternative formulation was selected.The physicochemical properties of alternative microemulsion formulations were studied,including particle size,polydispersion coefficient(PDI),Zeta potential,apparent morphological observation,p H value,dilution stability,freeze-thaw stability,in vitro dissolution,etc.Through the above data comparison,the optimal formula was obtained,and the optimal formula was tested by in vitro intestinal absorption experiment and HE staining to investigate the intestinal osmosis and intestinal mucosal toxicity of drug carrier.Results:Through screening and pseudo ternary phase diagram,the proportion of mixed surfactant was determined.The oil phase was Monocaprylin and the surfactant wasTween80 and the cosurfactant was Lanbrasol and the water phase was stilled water.The mixed surfactant ratio of 2:1 ratio,three microemulsion formula was selected for further research.Through studying the physical and chemical properties and ES capability study of the alternative microemulsion formula,the optimal formula F3 was obtained,which was composed of 30% Monocaprylin,26.67% Tween80,13.33% Lanbrasol and 30% water.The particle size was 179.2±18.79 nm,the polydispersion coefficient(PDI)was 0.394±0.02,the Zeta potential was-38.4±0.10,and the pH value was 6.4±0.10.Then the in vivo release study was carried out and the dissolution rate was the fastest in alternative formula,in accordance with the first-order rate model(R2=0.981).Compared with CMC-Na suspension of at same concentration,this formula significantly improved the intestinal absorption of the drug(p <0.05)and had no obvious stimulation to the intestinal mucosa Conclusion:It is proved that this study has developed a suitable microemulsion formula for oral administration of Esculetin.The preparation method is simple,stable,high solubility of Esculetin,and has no obvious adverse effect on intestinal mucosa.