Study on preparation and pharmacokinetics of gentiopicroside sustained release preparation

Gentiopicroside (GPS) is a natural component with anti-inflammatory, hepatoprotective, and other activities. However, its short half-life and insufficient residence time limit its clinical application. In this study, GPS was identified as a hydrophilic drug based on pre-formulation studies, and two sustained-release preparations were successfully developed, including gentiopicroside microporous osmotic pump tablets (GPS-MPOP) and gentiopicroside matrix sustained-release tablets (GPS-MRT). GPS-MPOP and GPS-MRT were prepared using single-factor experiments. In vitro release studies demonstrated that both preparations exhibited sustained release for 12 h. The release curve followed the Weibull model, and the release mechanism was governed by a combination of diffusion and erosion. In vivo pharmacokinetic study in New Zealand rabbits showed that the T_max of reference preparations (GPS-OT), GPS-MRT and GPS-MPOP were 0.25 h, 1.00 h (p ≤ 0.01) and 1.50 h (p ≤ 0.01); the C_max were 1108.11 ± 14.56 μg/L, 714.71 ± 10.24 μg/L (p < 0.0001) and 850.53 ± 4.80μg/L (p < 0.0001), and the t_1/2 were 1.30 ± 0.07 h, 5.36 ± 1.39 h (p < 0.0001) and 4.86 ± 0.28h (p < 0.0001), respectively. Compared with reference preparations, the relative bioavailability was 103.24% for GPS-MRT and 116.47% for GPS-MPOP, respectively. Both of the two sustained-release preparations prolonged drug release and reduced plasma concentration fluctuation, which provides a new strategy for clinical application of GPS.