The Study On SEDDS Soft Capsules Of β-Elemene

β-elemene, one of main components of zedoary, had considerable effectiveness for killing tumor cell and inhibiting the growth of tumor cell.β-elemene as anti-tumor drug, has wide antitumor spectrum, high efficiency, high safty and innocuity. Because of the poor solubility in water,β-elemene had low absorption in vivo by oral administration. Self-emulsifying drug delivery system (SEDDS) was selected as the carrier to prepare soft capsules to enhance absorption ofβ-elemene in this work.The basic physic-chemical properties, including stability, solubility and apparent partition coefficients (P_apP) ofβ-elemene, were investigated before establishing prescription. The results show that P_app ofβ-elemene was 2.69, which showed theβ-elemene was lipophilic.β-Elemene is unstable subjecting to lights and heat, whileβ-elemene is well stable in various excipients and aqueous solution at various pH values. In order to assay in vitro release and concentration in plasma ofβ-elemene, a high-performance liquid chromatography method was developed. A good specificity, sensitivity and reproducibility of this method made it particularly suitable for analysingβ-elemene.Soybean oil, ethyl oleate and Labrafac were used as candidates for oils phase. Labrasol, Tween85 and EL-20 were selected as candidates for surfactants. 1,2-propanol, transcutol and labrafil were used as candidates for cosurfactants. The experiments based on orthogonal design were carried out. Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region. The basic formulation which had the biggest efficient self-emulsification region was ethyl oleate / tween 85/ transcutol. The effects of oils, surfactants, drug and cosurfactants on formulation of SEDDS were investigated. The preparation process of SEDDS ofβ-elemene was optimized. Taking dissolution and emulsion particle size as indexes, the best formula was screened. The optimum formula of self-emulsification ofβ-elemene isβ-elemene/ethyl oleate/Tween85/transcutol = 55 / 45 / 60 / 40 (mass value) on the pseudo-ternary phase diagrams. After investigating the effect of temperature, disintegration time and dispersed methods on formulation of soft capsule, the optimum technologic process was established.The quality ofβ-elemene SEDDS were evaluated. The particles size was about 320nm and the size distribution was narrow. Zeta potential was about -3mV. emulsion droplet was near spherical shape under electron microscope. Appearance, disintegration time, dug content, emulsifying time and emulsion droplet size after self-emulsification has no change in cold-hot cycling test, accelerated test and long-term test showed the stability of β-elemene SEDDS was good. Meanwhile, the effect of different dispersed media, dispersed methods and the dilution times on the SEDDS were studied, and the the change of drug content and drug precipitation was not observed, which ensured theβ-elemene was in emulsion form in vivo.The pharmacokinetics of SEDDS soft capsules ofβ-clemene and conventional emulsion on dogs were investigated. SEDDS soft capsules ofβ-elemene and conventional emulsion were all followed the tow-compartment one-order dynamic model. Compared withβ-elemene conventional emulsion, the bioavailability of SEDDS soft capsules was 120.68%. The results of variance analysis and two one side t-test showed that the absorption degree of SEDDS soft capsules ofβ-elemcne and conventional emulsion were equal.