Comparative pharmacokinetic profiles of five poorly soluble pulchinenosides in different formulations from Pulsatilla chinensis saponins extracts for enhanced bioavailability

Abstract

Pulsatilla chinensis, a traditional Chinese medicine (TCM), has been used for treating amoebic diseases, vaginal trichomoniasis and bacterial infections over a long history. Now growing attention has been attracted to its antitumor activities. The purpose of this work was to compare the pharmacokinetic profiles of pulchinenosides in different formulations and to improve their oral bioavailability. Extracts of P. chinensis saponins were prepared for PRS-Na (salt forming), PRS-HPβCD (hydroxypropyl-β-cyclodextrin inclusion complex), PRS-O/W (oil-in-water emulsion) and PRS-silica (micronization), respectively. A simpler and more durable LC-MS/MS method was developed in this study for quantitative analysis of pulsatilla sapoin D, B7, B10, B11 and sapoin PD simultaneously. The four formulations enhanced saponins oral bioavailability to varying degrees, as PRS-HPβCD > PRS-silica > PRS-O/W > PRS-Na, which indicated that water-soluble preparations can obviously improve the solubility of saponins, and are helpful to increase bioavailability. In particular, hydroxypropyl-β-cyclodextrin inclusion complex was the most effective way to promote absorption of saponins, raising the F values (bioavailability) >20 times. Therefore, P. chinensis saponin molecules can be slowly released by emulsion and micronization, which can avoid the enormous Cmax appearing in HPβCD, considering the pharmacokinetics profiles. However, appropriate pharmacokinetic parameters were observed in PRS-Na, although the F value was minimum among the four preparations.

An integrated strategy using UPLC–QTOF-MSE and UPLC–QTOF-MRM (enhanced target) for pharmacokinetics study of wine processed Schisandra Chinensis fructus in rats

“…Currently, LC-coupled to triple-quadrupole mass spectrometry (QqQ-MS), operating in multiple-reaction monitoring (MRM) mode and this technique has been the first choice for quantitative analysis because of its high sensitivity and selectivity against a complex matrix background [4][5][6][7]. The limitations of QqQ-based method are obvious, such as low-resolution (LR), inability for untargeted analysis, and dependencies on reference substances.…”

Oral Bioavailability, Tissue Distribution, Metabolism, and Excretion of Panduratin A from Boesenbergia rotunda Extract in Healthy Rats

“… 40 By promoting water solubility, the bioactive substances could be more readily absorbed, resulting in increases in plasma levels and oral bioavailability. 41 …”

Influence Factors of the Pharmacokinetics of Herbal Resourced Compounds in Clinical Practice

“…Finally, they found that these two newly synthesized conjugates exhibited approximate 11-13 times longer t 1/2 in vivo than ROP alone, showing good absorption following subcutaneous administration [105]. In addition, other technologies like micronization, salt formation, and hydroxypropyl- β -cyclodextrin inclusion were reported to enhance oral bioavailability of target compounds [106].…”