Effect of Micronization on Panax notoginseng: In Vitro Dissolution and In Vivo Bioavailability Evaluations

Abstract

Panax notoginseng (PN) has become the most widely used dietary supplement and herbal in Asian countries. The effect of micronization on PN is not entirely clear. The aim of this study was to investigate the effects of particle size of Panax notoginseng powder (PNP) and the potential to improve the bioavailability. The results showed that particle size reduction significantly changed the Panax notoginseng saponins (PNS) in vitro dissolution and in vivo pharmacokinetics. The size of the Panax notoginseng powder (PNP) ranges from 60 to 214 μm. The surface morphology and thermal properties of PNP were extensively characterized, and these changes in physicochemical properties of PNP provide a better understanding of the in vitro and in vivo release behaviors of PNS. The in vitro studies demonstrated that the dissolution of PNS and particle size were nonlinear (dose- and size-dependent). The pharmacokinetics parameters of PNP in rats were determined by UHPLC-MS/MS. Powder 4 (90.38 ± 8.28 μm) showed significantly higher AUC_0-T values in plasma (P < 0.05). In addition, we also investigated the influence of the hydrothermal treatment of PNP. The results showed that the PNS in vitro release and in vivo bioavailability of PNP pretreatment at 40°C were the highest. This suggests that PNP with a particle size of around 90 μm and heat pretreatment at 40°C would be beneficial. These results provided an experimental basis, and it was beneficial to choose an appropriate particle size and hydrothermal temperature when PNP was used in clinical treatment.

Figure 1

(a) Morphological appearance and PLM images of the PNP with different particle sizes, (b) SEM and PLM images of the hydrothermally treated PNP, and (c) structure of notoginsenoside R₁ and ginsenosides Rg₁ and Rb₁.

Figure 2

Dissolution profiles of the PNP in pure water (A ∼ H) and simulated gastric fluid (a ∼ h). A, E, a, e: notoginsenoside R₁; B, F, b, f: ginsenosides Rg₁; C, G, c, g: ginsenosides Rb₁; D, H, d, h: PNS. 1 ∼ 6 correspond to Powders 1 ∼ 6, and 30, 40, 50, and 100°C correspond to the PNP treated at different hydrothermal temperatures.

Figure 3

MRM chromatograms and the plasma concentration-time profiles of notoginsenoside R₁, Rg₁, and Rb₁ in rats following intragastric administration of different sizes of PNP at a dose of 540 mg/kg. A: blank rat plasma, B: blank plasma spiked with notoginsenosides and IS, C: rat plasma collected at 30 min after intragastric administration of 540 mg/kg PNP. a, d: notoginsenoside R₁; b, e: ginsenosides Rg₁; c, f: ginsenosides Rb₁. Samples 1 ∼ 6 correspond to Powders 1 ∼ 6, and 30, 40, 50, and 100°C correspond to the PNP treated at different hydrothermal temperatures.