The Study Of Tanshinone ⅡA Oral Self-microemulsifying Drug Delivery Systems

TanshinoneⅡA is the diterpene quinone compound extracted from the root of the labiate plant,Salvia miltiorrhiza. It was widespread concerned by the academic community for a variety of biological activity, such as antimicrobial, anti-oxidation, expansion of coronary artery, increasing cardiac blood flow, anti-platelet, improving memory obstacles and significient anti-tumor activity. As a hydrophobic ingredient in the salvia, the low solubility in water and poor absorption of solid administration cause it difficult to make appropriate preparations and influence the clinical application. In this study, we designed and prepared the Tan-ⅡA SMEDDS, which increase its dissolution and bioavailability significiently through release assay in vitro and pharmacokinetics research in dogs. The results provided a new avenue in the development of this medicine.In this paper, the quantification of Tan-ⅡA was determined by RP-HPLC. The results showed that Tan-ⅡA is of good linearity (r=0.9998) in the range of 0.002 ~ 0.048 mg / ml, a good lipophility of Tan-ⅡA in the octanol - water system make it suitable to prepare SMEDDS. The DSC analysis showed that Tan-ⅡA was stable up to 250℃.Studying the balance solubility in different oil and surfactants and drawing the pseudo-ternary phase diagrams, self- emulsifying drug delivery system was optimized by comparing the emulsion area and the appearance. On the basis of this experiment, MCT, Cremophor RH40 and Propylene glycol were selected as oil, emulsifiers and co-emulsifiers respectively to prepare the self-emulsion formulations. The Km is 4:1.We studied the appearance, size and morphology of Tan-ⅡA self-emulsion formulations. Tan-ⅡA SMEDDS was transparent oil-red solution. The TEM results showed that the regular spheris particles were distributed uniformly in the emulsion with the average size of about 40 nm. The stability assay showed that the emulsion could be stable within eight hours.The dissolution of Tan-ⅡA SMEDDS was determined through the direct release medicine method and the overall balance reverse dialysis method. The results showed that the dissolution of Tan-ⅡA was quick and more than 95 percents of the drug was completed within 10 min in the direct release medicine assay. The overall balance reverse dialysis assay showed that about 50 percents of the drug were released in free form within 30 min.In this paper, the HPLC method used for the analysis of Tan-ⅡA isolated from dog plasma was established to satisfied the kinetics study in the dogs. And then the pharmacokinetics in dogs of the Tan-ⅡA SMEDDS was studied preliminarily comparing with the Tan-ⅡA suspension.In conclusion, the results showed that SMEDDS is suitable for the Tan-ⅡA preparation, which could increased the stability and the dissolution of Tan-ⅡA obviously, leading to its bioavailability enhanced finally. SMEDDS provided a new avenue for the development of drugs with poor water-soluble, instable and low bioavailability.