Studies On The Content Of Swertia Pseudochinensis Hara-Silymarin Soft Capsules And The Pharmacokinetics Of Active Component

Dangfeiliganning capsules is a compound preparation containing Swertia pseudochinensis Hara and Silymarin. The Silymarin and some main active components in Swertia pseudochinensis Hara such as oleanolic acid（OA） are nearly insoluble in water. So in this paper, we developed the soft capsules of Swertia pseudochinensis Hara and Silymarin, to increase their dissolution rates, thus to elevate the bioavailability of this preparation.Firstly, gentiopicroside（GPS） and OA were selected as the index components for Swertia pseudochinensis Hara, and then the HPLC-UV methods were developed respectively to determine the concentrations of GPS and OA in Swertia pseudochinensis Hara extracts. The concentrations of GPS and OA in different parts of Swertia pseudochinensis Hara were detected, the result of this experiment was that the concentrations of GPS and OA differed greatly among different parts of Swertia pseudochinensis Hara. So it was reasonable for Swertia pseudochinensis Hara to be used in the form of entire plant. And when Swertia pseudochinensis Hara was extracted, attention should be paid to the sampling to be as uniform as possible. The extraction process of Swertia pseudochinensis Hara was optimized by orthogonal design, and the optimum extraction method was: Swertia pseudochinensis Hara should be shattered to pass through the sieve with 850μm pore size totally, and should be soaked for 1 h before extracting. 85% alcohol was chosen as the extracting solvent, and the first time a twentyfold volume of 85% alcohol should be added to the Swertia pseudochinensis Hara powder to extract at 80±5℃for 1 h, and the second time a twelvefold volume should be used.With the self-made extracts of Swertia pseudochinensis Hara and Silymarin as the main active components, the formulation of Dangfeiliganning soft capsules content was screened. HPLC-UV method was set up to determine silybin’s concentration. The silybin’s dissolution rate was used as index to compare the self-made soft capsules content’s with the commercially available capsule’s dissolution in different media. The stability of this content under the situations of high temperature and highlight were investigated initially, and it was found that the contents of OA and silybin were stable under these situations. The dissolution rates of this self-made content were significantly higher than the commercially available capsule in the media selected.In order to elevate the bioavailability preferably, and to decrease the formulation dose, the OA（active component of Swertia pseudochinensis Hara）-silymarin soft capsules preparation was explored. Firstly, OA was changed to OA-Na by reaction with NaOH in ethanol, and the reaction was assessed simply. And then the soft capsules formulation was prepared with OA-Na and Silymarin as main components. A UV method was used to determine the concentration of Silymarin. The dissolution rates of OA and Silymarin were used as indices to inspect the self-made soft capsules content’s dissolution in different media. OA’s dissolution rate was significantly larger in 0.5%SDS solution from self-made soft capsules than from commercially available OA tablets.OA’s Pharmacokinetics and bioavailability were studied in rats with the self-made OA（active component of Swertia pseudochinensis Hara）-silymarin soft capsules as the test preparation, and commercially available OA tablets as the reference preparation. HPLC-MS method was developed to analyze OA in rats’ blood plasma. The relative bioavailability and pharmacokinetic parameters of OA were obtained by the trapezoid method. The main pharmacokinetic parameters were inspected by The Student’s test, and the result was that there were significant difference in the main pharmacokinetic parameters between the two preparations except T_max1. The relative bioavailability of OA in self-made soft capsules was 194.66%.