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AIM: To investigate the effect of release behavior of sustained-release dosage forms of sinomenine hydrochloride (SM·HCI) on its pharmacokinetics in beagle dogs. METHODS: The in vitro release behavior of two SM·HCI 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·HCI pharmacokinetics was investigated and compared. RESULTS: The optimal SM·HCI sustained-release formulation was achieved by mixing slow-and rapidrelease pellets (9:1, w/w). The SM·HCI 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% vs68.7%. From a pharmacokinetic standpoint, the 24-h SM-HCI sustainedrelease pellets had longer t_(max) and lower C_(max) compared to the 12-h sustained-release tablets, the t_(max) being 2.67±0.52 h vs 9.83±0.98 h and the C_(max) being 1334.45±368.76 ng/mL vs 893.12±292.55 ng/mL, respectively. However, the AUC_(0-tn) of two SM·HCI dosage forms was comparable and both preparations were statistically bioequivalent. Furthermore, the two preparations had good correlations between SM·HCI 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.
AIM: To investigate the effect of release behavior of with-release dosage forms of sinomenine hydrochloride (SM·HCI) on its pharmacokinetics in beagle dogs. METHODS: The in vitro release behavior of two SM·HCI 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·HCI pharmacokinetics was investigated and compared. RESULTS: The optimal SM ·HCI has sustained-release was was achieved by mixing slow-and rapid release pellets (9:1, w/w). The SM·HCI release profiles of the sustained-release pellets were scarcely affected by the pH of the dissolution medium. Release from The 12-h sustained-release tablets were markedly quicker than that from the 24-h sustained-release pellets, the virtually released up to 12-h was 99.9% vs68.7%. From a pharmacokinetic standpoint, the 24-h SM- HCI sustainedrelease pellets had Long t_(max) and lower C_(max) compared to the 12-h sustained-release tablets, the t_(max) being 2.67±0.52 h vs 9.83±0.98 h and the C_(max) being 1334.45±368.76 ng/mL Vs 893.12±292.55 ng/mL, respectively. However, the AUC_(0-tn) of two SM·HCI dosage forms was comparable and both preparations were balanced ly bioequivalent., the two preparations had good correlations between SM·HCI percentage absorption in Summary: The in vitro release properties of the toxicity properties of the harmful microorganisms in in vivo. administering the dosage forms is a promising strategy for obtaining the optimal in vivo pharmacokinetic Characteristics and safe the therapeutic drug concentration-time curves.