Preparation, characterization and pharmacokinetics of extended-release tablets of marine polysaccharide drug

Abstract

Cardiovascular disease (CVD) is a class of chronic diseases, and the patients need long-term medication. Propylene glycol alginate sodium sulfate (PGAS) obtained from marine algae, which has been applied to clinical treatments of CVD in China for 30 years. However, none PGAS have been formulated in extended-release tablet. Herein, we developed an extended-release (ER) tablet of PGAS fabricated by wet granulation method using hydroxypropyl methylcellulose (HPMC) to prolong the duration of efficacy. Furthermore, we investigated its in vitro data and in vivo pharmacokinetic characteristics in beagle dogs. The commercial tablets exhibited a rapid release behavior and more than 75% of PGAS was released within 1 h, while 91.09 ± 1.65% of PGAS released from the PGAS ER tablets in 12 h, which followed the non-Fickian diffusion mechanism in vitro. Moreover, the pharmacokinetic profiles of PGAS in beagle dogs emerged a prolonged release of the ER tablets within 48 h. Compared with the commercial tablets, the Tmax, AUC and bioavailability of PGAS ER tablets are markedly increased by 6-fold, 1.71-fold and 2.17-fold, respectively. Such data further demonstrated PGAS ER tablet as a promising agent for treating CVD.