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

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 r² = 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.