Dissolution Of Silymarin Solubilized Granules In Vitro And Pharmacokinetic Studies In Piglets

Silymarin?SLY?is a flavone lignan compound extracted from plants.The active ingredientsof traditional Chinese medicine is complex.The main active components in silybin are silybin,silychristin,silidianim,isosilybin.Silybin,which has the highest activity content,accounts for about 33%of silymarin.Silymarin's pharmacological effects are mainly manifested in the treatment of liver diseases,such as cirrhosis,fatty liver,metabolic toxic liver injury,acute and chronic hepatitis,and other liver diseases.Therefore,silymarin is a safe,low-toxicity,widely pharmacological medicine.However,the effectiveness of SLB as liver disease remedy was discounted by its poor water solubility and low bioavailability after oral administration.Therefore,continuously improving the dosage form of silymarin,improving or finding a novel dr?g delivery system,enhancing the solubility of silymarin,and improving the bioavailability of silymarin are of great significance to the further development of silymarin.The aim of the study was tocompare the pharmacokinetics of silymarin solubilizing granulesandsilymarin ordinary premixes after administration of 50 mg·kg^-1·b.w and in vitro dissolution test.The analysis of dissolution percentage and the comparison of pharmacokinetic parameters provide theoretical basis for further development of silybin solubilized granules and clinical use of piglets.The dissolution test were performed in compliance with Chinese Veterinary Pharma-copoeia using apparatus 1?baskets?at 100 r·min^-1.The dissolution medium selected pH1.2hydrochloric acid buffer solution,pH4.3 acetic acid buffer solution and pH6.8 phosphate buffer solution for simulatedpiglet gastrointestinal environment.0.5%Tween-80 Surfactant was added to meet the sink condition.The dissolution sampes withdrawn from the dis-solution medium were detected by UV spectrophotometric methods and cumulative release were computed.The results showed that the silymarin ordinary premixeswas dissolved in35.02%³8.70%for 6 hours in different dissolution media.However,silymarin solubilizing granules in different dissolution medium reached 37.65%⁵1.65%in 20 minutes and dis-solution medium reached 82.92%⁹9.70%in 6 h.The dissolution rate of silymarin solu-bilized particles was the fastest and most complete in the medium of pH6.8.Pharmacokinetic studied with sixteen healthy crossbred weanling pigs?Yorkshire×Landrance?,weighting 13.68 kg±0.57 kg.The weanling pigs were divided intotwogroups randomly,eight pigs in each group.Two groups received silymarin solubilizing granulesandsilymarin ordinary premixes,at the 50 mg of active ingredient per kg bodyweight respectively.The solubilizing granules containing 3.92%silybin and the ordinary premixes containing 3.10%of silybin were administered to pigs directly by stomach tube.Intra-venousing blood at various time points after administration.The obtained plasma samples were placed in the anticoagulant tube of heparin and centrif?ged to take the supernatant,Stored at-20?.Plasma samples extracted were detected by high performance liquid chromatography?HPLC?.The plasma concentration-time data was fitted with Winnonlin5.2.1 for non-compartmental model.After receiving a single oral dose of silymarin solubilizing granules,the main pharma-cokinetic parameters of pigs were as followed:the T_max was 0.48±0.06 h,the AUC was1299.19±67.61 ng·mL^-1·h,t_1/2 was 2.02±0.47 h,the C_max was 1190.02±246.97 ng·mL^-1;and after administration of silymarin ordinary premixes,the T_max was 0.48±0.06 h,the AUC was569.98±166.28 ng·mL^-1·h,t_1/2 was 1.68±0.71 h,the C_max was 411.35±84.92 ng·mL^-1.Compared the pharmacokinetics and in vitro dissolution of silymarin solubilized particles and meats were in this study.The experimental results showed that the dissolution rate of silybin solubilizing particles in vitro was higher than that of silymarin ordinary pre-mixesin different media.The pharmacokinetic results showed that the C_max of silymarin solubilized particles in pigs was much higher than that of the premixture,and AUC was also significantly increased.The statistical analysis also found that silybin solubilizing particles and premixture were significantly different in C_maxax and AUC explain that silymarin solubilizing particles absorb better in the body.The purpose of reducing the dosage and increasing the curative effect can be achieved inclinical application.