Modeling of In Vitro Dissolution Profiles of Carvedilol Immediate-Release Tablets in Different Dissolution Media.

Abstract

Quantitative evaluation of drug dissolution characteristics based on mathematical models is essential to understand and predict a particular drug release profile. In this study, model-dependent evaluation of the dissolution kinetics of reference and five test products (25-mg, immediate-release (IR) tablets) of an antihypertensive drug, carvedilol, was carried out using the DDSolver® program. The effects of pH (pH 1.2, 4.5, and 6.8) and various media with/without 0.5% (w/v) anionic, cationic, and nonionic surfactants (sodium lauryl sulfate (SLS), hexadecyltrimethylammonium bromide (CTAB), and polysorbate 80) on the dissolution kinetics of the bioequivalent IR products of carvedilol were investigated. The Weibull-1 model was fitted successfully to the dissolution data of all products at pH 1.2 and pH 4.5, as well as in the pH 6.8 medium with CTAB according to the model goodness of fit (r2 = 0.981-0.999, AIC = 14.5-42.6, MSC = 1.99-5.25). Model fitting produced good fits to Gompertz-1 for all products at pH 6.8 without a surfactant (r2 = 0.975-0.998, AIC = 28.3-55, MSC = 2.53-5.82). For pH 6.8 media containing SLS or polysorbate 80, Logistic-2 was fitted successfully to the dissolution data of all products (r2 = 0.974-0.999, AIC = 20.9-52.1, MSC = 1.90-5.69). Overall, the model-dependent analysis of in vitro dissolution data indicated in vitro equivalence of the reference and test products of carvedilol in each medium in terms of kinetic models, suggesting that it would have an important role in developing generic drug products of the BCS class II drug carvedilol.