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Silibinin (silybin or silibinin, SLB) is extracted from the fruit of the the Compositae milk thistle (Silybum marianum L. Gaertn) an isolated flavonoids have good treatment of hyperlipidemia, eliminate free radicals, Anti-hepatic lipid peroxidation role drugs efficacy of liver injury and repair. However, due to its water-soluble and fat-soluble, orally difficult to absorb low bioavailability, thus greatly limiting its clinical application; many SLB preparations, silybin phospholipid complex (silybin-phospholipid complex, SLC) can significantly improve the SLB the bioavailability of concern in recent years. Hepatitis, high cholesterol and other diseases require long-term therapy, long-term medication. Listed SLB preparations tablets, capsules, etc. ordinary oral dosage forms, medication frequently, usually administered 3 times daily medication of patients is more inconvenient and after administration plasma concentration fluctuations. This topic tentative on the basis of the phospholipid complex developed SLB sustained-release formulations, on the one hand to improve the solubility of the SLB increase its bioavailability and improve the clinical utility; other hand slow drug release, extend the efficacy smooth plasma concentration, reducing the frequency of administration, and improve patient medication compliance; also hope to achieve SLC secondary development of the drug product. Firstly established by HPLC intestinal circulating fluid SLB SLB and SLC absorption behavior in the rat small bowel segment, using rat intestinal loop model compared and investigated the SLC absorption characteristics in rat bowel . The results show that the SLB and SLC presented a kinetic characteristics of the absorption in the small intestine, the SLC the cumulative percent absorption, and absorption rate SLB 1.71 times and 2.2 times, respectively; divided bowel trial, SLC each bowel (duodenal absorption percentage of the intestine, the jejunum, ileum, colon) and the intestinal wall permeability coefficient There was no significant difference (at α = 0.05, P gt; 0.05), the SLC are in the whole intestinal absorption. Hydroxypropyl methyl cellulose (HPMC) skeletal material, polyvinyl pyrrolidone (PVPK30) as a solubilizer, spray-dried lactose (Lactose) as a filler, the direct powder tabletting process, developed a day administration times SLB sustained-release tablets, and the use of orthogonal experimental design to optimize the prescription process, carried out the in vitro release test, similar factor as the evaluation of the release data. The results show that the 2 h preferably prescription tablets prepared in phosphate buffer (pH 7.8) containing 0.5% Brij35 release 15% to 25% release of 35% to 45%, 4 H, 8 H release 75% ~ 85%, 12 h release more than 90%. Vitro release of sustained-release tablets, curve fitting, and the results show that the the Peppas equation can be a good description of the SLB in vitro release characteristics. Peppas equation fitting that the release mechanism of the skeleton dissolution. This paper examines the homemade SLB sustained-release tablets stability under accelerated test conditions. The results show that this product to simulate commercial packaging (aluminum foil vacuum packaging) RH 75%, temperature 40 ℃ under the conditions of the appearance of the place three months did not change significantly, drug content and release qualified. Established SLB by HPLC dog plasma, the method has good linearity and high recovery rate, the intra-day precision RSD lt; 15%. To commercially available the SLC Capsules water LIN Jia parameters for the test reagent preparation, homemade sustained-release tablets, two-cycle double cross-experiment to study the pharmacokinetic behavior and bioavailability SLB sustained-release tablets in Beagle dogs. The results showed that the plasma concentration - time curve to parse configuration process in the body compartment model in line with the two-compartment model. Compared with the reference formulation, the peak time of sustained-release tablets (T max ) and the mean residence time (MRT) was significantly prolonged peak concentration (C max ) significantly reduced, the release effect is obvious, the relative bioavailability (75.9 ± 12.8)%.
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