Development of a Predictive Flow Through Cell Dissolution Method for Carbamazepine Modified‐Release Tablets

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Abstract
Predictive in vitro dissolution methods are crucial for anticipating in vivo drug performance, particularly for poorly soluble drugs like carbamazepine. In vitro ‐ in vivo correlations (IVIVC) link dissolution characteristics to pharmacokinetics, facilitating bioequivalence studies and reducing reliance on clinical trials. This study aimed to develop a predictive in vitro dissolution method using USP Apparatus 4 for a modified‐release carbamazepine formulation, optimizing dissolution conditions by using principles of the IVIVC methodology. A Box–Behnken experimental design optimized dissolution parameters, including sodium lauryl sulfate concentration, flow rate, and glass bead quantity. IVIVC was assessed for a single formulation, using the Wagner‐Nelson deconvolution method and a two‐step scaling approach involving Levy plot transformation and time‐scale alignment. Gohel's reconvolution equation predicted absorbed fractions and plasma concentrations. The method's discriminatory power was evaluated using immediate‐release (IR) and modified‐release (MR) carbamazepine formulations. The refined IVIVC model achieved r 2 = 0.9905, with AUC 0‐t and C max prediction errors of −6.09% and −1.94%, respectively. The method effectively distinguished IR from MR formulations, with discriminatory analysis (f1, f2, DE, MDT) confirming its sensitivity. A predictive flow‐through cell dissolution method was successfully developed, providing a robust tool for bioequivalence studies and generic formulation development. This approach supports formulation optimization and increases the likelihood of successful in vivo bioequivalence outcomes.
Funding Information
  • Universidad Nacional de Colombia

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