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In vitro - In vivo correlation modeling of an oxcarbezapine extended-release formulation using numerical
Maziar Kakhi1, Hansong Chen2, Jason Chittenden3
1Division of Product Quality Research, Office of Product Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Abstract:
An in vitro - in vivo correlation (IVIVC) for an oxcarbazepine (OXC) extended-release formulation, originally submitted as part of a regulatory submission and found to be inadequate, was re-evaluated using two-stage numerical deconvolution and found to be predictively robust by meeting internal and external validation criteria. This result was achieved by enhancing the unit impulse response (UIR) characterization and using nonlinear IVIVC mapping functions. The predictive IVIVC was then applied to determine dissolution acceptance criteria, which showed good agreement with the currently approved criteria for the lower bound of dissolution. Furthermore, IVIVCs that linked in vitro drug release of OXC to the in vivo response of the active metabolite showed higher overall accuracy compared to IVIVCs that linked OXC's in vitro drug release to its own in vivo response. This finding was attributed to the stronger rank-order correlation between the active metabolite's pharmacokinetics and the in vitro data.
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