Aim: To investigate the effect of release behavior of sustained-release dosage forms of sinomenine hydrochloride (SM.HCl) on its pharmacokinetics in beagle dogs.
Methods: The in vitro release behavior of two SM.HCl dosage forms, including commercial 12-h sustained-release tablets and 24-h sustained-release pellets prepared in our laboratory, was examined. The two dosage forms were orally administrated to beagle dogs, and then the in vivo SM.HCl pharmacokinetics was investigated and compared.
Results: The optimal SM.HCl sustained-release formulation was achieved by mixing slow- and rapid-release pellets (9:1, w/w). The SM.HCl release profiles of the sustained-release pellets were scarcely influenced by the pH of the dissolution medium. Release from the 12-h sustained-release tablets was markedly quicker than that from the 24-h sustained-release pellets, the cumulative release up to 12-h was 99.9% vs 68.7%. From a pharmacokinetic standpoint, the 24-h SM.HCl sustained-release pellets had longer tmax and lower Cmax compared to the 12-h sustained-release tablets, the tmax being 2.67+/-0.52 h vs 9.83+/-0.98 h and the Cmax being 1 334.45+/-368.76 ng/mL vs 893.12+/-292.55 ng/mL, respectively. However, the AUC(0-tn) of two SM.HCl dosage forms was comparable and both preparations were statistically bioequivalent. Furthermore, the two preparations had good correlations between SM.HCl percentage absorption in vivo and the cumulative percentage release in vitro.
Conclusion: The in vitro release properties of the dosage forms strongly affect their pharmacokinetic behavior in vivo. Therefore, managing the in vitro release behavior of dosage forms is a promising strategy for obtaining the optimal in vivo pharmacokinetic characteristics and safe therapeutic drug concentration-time curves.