Preparation of Panax notoginseng flower saponins enteric-coated sustained-release pellets and its pharmacokinetics and in vitro-in vivo correlation

Background Panax notoginseng flower saponins (PNFS) are great contributions towards the biological activity of Panax notoginseng flower (PNF). However, some ginsenoside monomers can be hydrolyzed by the acidic environment in the stomach, resulting in a decrease in their oral bioavailability. Therefore, we created PNFS enteric-coated sustained-release pellets (E-PNFS) to improve their oral bioavailability. Methods The PNFS uncoated pellets (N-PNFS) and E-PNFS were prepared by fluidized bed coating technology using Eudragit NE30D as the sustained-release agent and Opadry as the enteric-coated agent. The single-factor investigation was used to determine the optimal prescription. The E-PNFS were visualized by scanning electron microscopy (SEM) and evaluated for roundness, bulk density, resting angle, hygroscopicity and stability. The plasma drug concentration in SD rats was determined by the UPLC-MS/MS method, and pharmacokinetic parameters were calculated by Phoenix WinNonlin5.2 software. The in vivo absorption fraction was calculated by Wagner-Nelson method The in vivo absorption and in vitro release percentages were linearly regressed by the least square method. Results According to the prescription screened out by the single factor investigation, E-PNFS was successfully prepared, and had good release properties in vitro along with a good measure for roundness, flowability and stability. Compared with N-PNFS, E-PNFS showed decreased Cmax, increased AUC, and an extended MRT and Tmax. Rb1, Rb2, Rb3 and Rc in E-PNFS showed a good correlation between in vitro release and in vivo absorption. Conclusions The successfully prepared E-PNFS were able to improve the oral bioavailability of PNFS in SD rats in general. The in vitro release behaviors of Rb1, Rb2, Rb3 and Rc in E-PNFS correlated well with the in vivo absorption properties.