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Dissolution and pharmacokinetic properties of alkaloids and flavonoids in a Xiexin multiple-unit drug delivery system.

Alkaloids from Rhizoma coptidis and flavonoids from Radix scutellariae were prepared in 2 separate units using a Xiexin multiple-unit drug delivery system (XXMU) to avoid the interactions that occur in the Xiexin decoction (XXD), which reduce oral bioavailability. Similarity factors (f 2 ) were calculated for the release of each component, and 4 equations were fitted to describe the release mechanism. In vivo pharmacokinetic studies were undertaken in rats to compare orally administered XXMU to a XXD powder suspension. No significant differences in the in vitro release properties of the 4 main components were observed between the individual pellets and the entire XXMU delivery system. The release mechanisms for coptisine, berberine, palmatine and baicalin from XXMU involved non-Fickian transport, non-Fickian transport, Fickian diffusion and zero-order release, respectively. The AUC(0-6 h), Cmax1(0-0.5 h) and Cmax3(2-6 h) values for berberine were significantly higher for XXMU than for XXD, but significant differences between the 2 dosage forms were not observed for pharmacokinetic parameters of baicalin. Interactions between flavonoids and alkaloids were reduced in XXMU, and the oral bioavailability of berberine was improved. The successful application of a multiple-unit drug delivery system may provide a method to improve the oral bioavailability of traditional Chinese medicines with multiple components.