Comparison of dissolution profiles of carbamazepine tablets by paddle method and flow-through cell method and study on in vitro-in vivo correlation
WU Bin
ZHU Xiao-yue
ZHU Xue-bin
ZHANG Shu-dong
HU Qin
WANG Lin
WU Zhao-wei
Abstract：Objective:Carbamazepine is a BCS Class II drug with a narrow therapeutic window,for which dissolution is the rate-limiting step for absorption.However,the current dissolution testing method has several limitations,including inconsistent rotational speeds(e.g.,150 r·min-1 for the 0.2 g strength),single-point quality control(where a two-point method is more appropriate for narrow therapeutic window drugs),and a lack of in vitro-in vivo correlation(IVIVC).Therefore,it is necessary to establish an IVIVC-based dissolution method to guide generic drug bioequivalence evaluation.Methods:The paddle and flow-through cell methods were used to determine the dissolution profiles of reference products(Novartis Beijing,0.2 g and Sun Pharma Japan,0.1 g)in five different media.GastroPlus modeling was employed to identify the dissolution conditions with the best IVIVC.These optimized conditions were then applied to evaluate the dissolution behaviors of 9 generic products.Results:The optimal dissolution conditions for both paddle and flow-through cell methods with the highest IVIVC were identified.Both methods effectively discriminated between products from different manufacturers,and the flow-through cell method demonstrated superior sensitivity in detecting intrinsic quality differences between generic and reference products.Conclusion:It is recommended to revise the current dissolution standard for carbamazepine tablets by replacing the paddle method with the flow-through cell method and implementing a two-point quality control approach.
Keywords：CarbamazepineGastropluspaddle methodflow-through cell methoddissolution profilef2 factor
Publication Date：2026-03-15
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：9( 521-529 )