Journal
BIOLOGICAL & PHARMACEUTICAL BULLETIN
Volume 24, Issue 4, Pages 409-413Publisher
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.24.409
Keywords
Sho-saiko-to; tolbutamide; dissolution; glycyrrhizin; Chinese medicine
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Dissolution rate is considered an important factor affecting absorption and efficacy after the oral administration of tolbutamide. Since in many cases traditional Chinese medicines, including Sho-saiko-to (TJ-9, Xiao Chaihu Tang), are taken,vith other drugs, it is likely that the dissolution and absorption of concomitant drugs in the gastrointestinal tract are influenced by the presence of traditional Chinese medicines. In this study, the effects of TJ-9 on the in vitro dissolution of tolbutamide were examined. We carried out the dissolution test of tolbutamide in the absence or presence of traditional Chinese medicines (Kakkon-to, TJ-1; Hachimi-jio-gan, TJ-7; Chorei-to, TJ-40; Shakuyaku-kanzo-to, TJ-68; TJ-9; Glycyrrhizae Radix, CR; glycyrrhizin, GL) by using a pH 1.2 dissolution medium. Tolbutamide was determined by HPLC assay, The moment parameters, i.e., mean dissolution time (MDT), and the dissolution rate constant up to 20 min (k(d)) were estimated from the dissolution profiles on the basis of the first-order kinetics. Preparations containing GR, namely TJ-1, TJ-9 and TJ-68, significantly reduced the k(d) and increased the MDT of tolbutamide, while TJ-7 and TJ-40 had no effect on the early dissolution profile of tolbutamide. The extent of decrease in the k(d) in the presence of TJ-1, TJ-9 and TJ-68 was dependent on their GR contents. Similar inhibitory effects on the dissolution rate of tolbutamide were observed when GR alone was added to the test medium. In addition, CL, a major constituent of GR, induced a 50% increase in MDT and a 30% decrease in k(d). The above results indicate that Chinese traditional preparations containing GR have an inhibitory effect on the DI,vitro dissolution of tolbutamide, which is derived from CL in the preparations.
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