Design Of Dispersible Tablets And Softgel Capsules Of Silymarin

Silymarin, a polyphenolic flavonoid isolated from the seeds of milk thistle [Silybum marianum (L.) Gaertner], is composed mainly of silibinin with small amounts of other silibinin stereoisomers, namely isosilibinin, silidianim, silichristim, silibonol. Silibinin is the principal component and main active substance of silymarin. Silymarin or silibinin is used clinically for the treatment of liver diseases, which has the advantage of good therapy and little side-effect. Major problem involved in the development of an oral dosage form of this drug is the extremely poor aqueous solubility which decreases the dissolution rate of silymarin and further limis its oral absorption. To act further quickly and be suitable to industrial production, dispersible tablets and softgel capsules were designed and prepared.Firstly, UV spectrophotometry was developed and validated for the stability of silymarin as well as its formulation optimization and quality control. Secondly, an HPLC-UV method was applied to detect the concentration of silibinin which was chosen as the mark component of silymarin and to evaluate stability and quality of silymarin and silymarin preparation as well as to determine the plasma samples in dogs. The methods mentioned above are accurate, liable, convenient and rapid, which all fit the requirement of analysis.In the preformulation study, the physicochemical properties of silibinin were investigated. The result showed that the concentration of silibinin detected by HPLC in distilled water, HC1 solution(pH1.2)and phosphate buffer of various pH values appeared no change except in extremely low or high pH condition(pH <3 or pH >8)at 37 ℃. Especially when the pH values greater than 9 the stability of silibinin was very poor while when the pH values are between 6 and 8 its stability was much more better. The equilibrium solubility of silibinin in water is 51.06 Hg-mL^-1 at 37 ℃ and has higher values in basic buffer solutions; Tween 80 and poloxamer 188 are good solubilizers for silibinin; The apparent n-octanol/water partition coefficient (P_app) of silibinin is 989.0 and among the values of apparent n-octanol/phosphorate buffer of different pH values, a highest value was got when the pH value was 5.0. Moreover, the chemical stability of silymarin and silibinin were studied and the result showed that exposure to air, light, humidity and high temperature had little effect on the content of silymarin and silibinin.Based on the results of single-factor tests about the influence factors on disintegration time of dispersible tablets, the amounts range of silymarin and excipients were set. The formulation was optimized on the basis of four factors and three levels orthogonal design by evaluating cumulative dissolution percents in 90 min. Silymarin dispersible tablets were prepared according to the best components and preparing condition. Comparing dissolution rate of silymarin and...