Study on Integrated Pharmacokinetics of the Component-Based Chinese Medicine of Ginkgo biloba Leaves Based on Nanocrystalline Solid Dispersion Technology

Abstract

Background To improve the dissolution and bioavailability of the component-based Chinese medicine of Ginkgo biloba leaves (GBCCM), a novel nanocrystalline solid dispersion of GBCCM (GBCCM NC-SD) was first prepared. Methods GBCCM mainly containing high pure flavonoid aglycones (FAs) and terpenoid lactones (TLs) was used as the model drug. PVP K30 and SDS were used as solubilizers, combined stabilizers and carriers, and GBCCM NC-SD was prepared by high-pressure homogenization combined with freeze-dryer. Morphology and crystal characteristic of GBCCM NC-SD were analyzed. The dissolution and bioavailability evaluation were performed to investigate the feasibility of GBCCM NC-SD by in vitro dissolution and in vivo integrated pharmacokinetic models. Results After homogenizing for 30 cycles under the pressure of 650 bar and freeze-drying, GBCCM NC-SD with uniform quality would be obtained. The particle size, PDI and zeta potential were found to be 335.9 ± 32.8 nm, 0.29 ± 0.02 and −28.4 ± 0.7 mV respectively. Based on charged aerosol detector (CAD) technology, a new chromatographic method for simultaneous detection of eight components in GBCCM was developed. In vitro drug release study showed that the cumulative dissolution of FAs and TLs in GBCCM NC-SD increased from 12.77% to 52.92% (P < 0.01) and 90.91% to 99.21% (P < 0.05) respectively. In comparison with physical mixture of GBCCM and stabilizer (PM), the integrated pharmacokinetics AUC 0-t of FAs and TLs in GBCCM NC-SD were significantly increased (P < 0.05), and the T 1/2 of TLs was also significantly prolonged (P < 0.05). Conclusion This study demonstrated that novel GBCCM NC-SD was prepared using Polyvinylpyrrolidone K30 (PVP K30) and Sodium dodecyl sulfate (SDS) as a synergetic stabilizer and also provided a feasible way to improve the dissolution and oral bioavailability of poorly soluble candidate antihypertensive drugs.

Pharmacological activities and effective substances of the component-based Chinese medicine of Ginkgo biloba leaves based on serum pharmacochemistry, metabonomics and network pharmacology

“…The conditions were as follows: ion spray voltage was 3.5 kV, capillary temperature was 350 °C, collision voltage was 40 eV, the sheath and auxiliary gases flow rate were 35 and 10 (arbitrary units), respectively. The contents of GBCCM were analyzed by HPLC-CAD (Liang et al, 2022a). data of blank serum and GBCCM containing serum were imported into the software.…”