Research Of Self-microemulsifying Drug Delivery System Containing Bile Salts

Self-microemulsifying drug delivery system (SMEDDS) is usuallyused to increase the solubility, absorption and bioavailability, meanwhilereduce the toxicity and side effects of drug.In the study, pueraria lobata flavone (PTF) was selected as modeldrug, the content of oily phase, surfactants and co-surfactants wereoptimized on the basis of PTF-SMEDDS formulation by drawing ternaryphase diagrams and pseudo-ternary phase diagrams. Self-microemulsionefficiency, particle size and the drug loading were used to evaluated thenew SMEDDS formulation. The finally PTF-SMEDDS formulation wereconsisted of pueraria total flavonoids (30.0%), ethyl oleate (21.0%),cremophor RH-40(35.0%) and transcutol P(14.0%). The appearance ofoptimized formulation were dark brown and viscous liquid with90sself-emulsifying time, the droplet size and zeta-potential of the resultantmicroemulsion were34.46nm and-11.3mV respectively. The optimizedformulation was quite stable during six months.Bile salts were endogenous components of human which had surfaceactivity effect either, synthetic emulsifiers could be substituted by bilesalts to reduce the toxicity. The study partial replaced syntheticemulsifiers with sodium cholate, sodium deoxycholate and sodiumtaurodeoxycholate, and evaluated the emulsifying effect, particle size,zeta potential and stability of microemulsion. The results showed that thealternative of sodium cholate, sodium deoxycholate and sodiumtaurodeoxycholate were30%, the droplet sizes of microemulsion wereless than200nm.Microemulsion was used as solvent to extract PTF from traditional Chinese medicine Pueraria by combing high shear technology. Wheninvestigated the effect of methods on the extraction efficiency, we foundthat the PTF yields of refluxing method were slight more than that of highshear method and ultrasonic method, and the least extraction yields wereachieved in ultrasonic. In view of time saving by high shear method,orthogonal experiments were carried out to optimize the extractionconditions of microemulsion which contains bile salts by high shearmethod. The results showed that the solid-liquid ratio and dilution foldsof microemulsion exerted a significant effect on the extraction yields,meanwhile the proportion of sodium deoxycholate displayed lesssignificant effect. The optimized extraction conditions were1:15(w/v) ofsolid-liquid ratio,5folds dilute microemulsion and2mmol·L-1of sodiumdeoxycholate.