Forecasting in vivo pharmacokinetics of metformin HCl floating beads using Gastroplus® PBPK

利用 Gastroplus® PBPK 预测盐酸二甲双胍漂浮微球的体内药代动力学

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Abstract

BACKGROUND: Diabetes mellitus type II is expected to impact a large population worldwide. Among the available therapeutic options, Metformin hydrochloride is a key medication, particularly for those who cannot effectively manage the condition through changes in diet and lifestyle alone. This research aimed to predict their in vivo parameters from an in vitro release study by developing a physiologically based pharmacokinetic (PBPK) model by using Gastroplus (®) software. METHODS: Sodium alginate-based MH floating beads were prepared by dissolving different concentrations of sodium alginate in deionized water, incorporating MH (1 g) and calcium carbonate (1.5 mg) as a gas-forming agent, and mixing at 200 rpm. The air-free dispersion, achieved through 30 minutes of sonication, was dropped into a 5% w/v calcium chloride solution containing 5% v/v isopropyl alcohol via a syringe for cross-linking and bead formation. Beads were cured in the solution for 30 minutes to enhance mechanical strength, then filtered, washed, and air-dried for 24 hours, ensuring uniformity and stability for controlled drug delivery and the prepared beads were evaluated for their entrapment efficiency %, morphology, floating property and in vitro release Ultimately, using Gastroplus (®) software, to predict the pharmacokinetic profile of in vitro release results. RESULTS: Entrapment efficiency exhibited acceptable values, and the beads were smooth, and rounded in shape for all formulations. The beads remained afloat during the release study; the release study revealed that F1 to F5 showed asymptotic slow-release, while F6 and F7 gave shorter release times. The prediction of absorption indicated highest MH absorption was in the jejunum, then the duodenum. CONCLUSION: The prepared Beads had promising pharmacokinetic parameters and C max was close to MH modified released tablet.

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