Comparison of Dissolution Profiles and Serum Concentrations of Two Lamotrigine Tablet Formulations

摘要

>Objective: The aim of this study was to investigate the extent of variations in lamotrigine serum concentrations between two immediate-release tablet formulations. Data were compared with in vitro difference and similarity tests on dissolution profiles of the two formulations.>Methods: Dissolution characteristics of formulations A (reference) and B (test) were evaluated at three points spanning the physiologic pH range (pH 1.2, pH 4.5, pH 6.8). A model-independent approach of difference (f1) and similarity (f2) tests were applied to dissolution data. A clinical study was performed with 16 patients who were divided into two groups — one group received formulation A (n=9) and the other received formulation B (n=7). Lamotrigine steady-state concentrations were determined by high-performance liquid chromatography on a reverse-phase column.>Results: There were no statistically significant differences in lamotrigine serum concentrations between the two groups, although formulation B had slightly higher mean concentration values (formulation A: 3.97±4.1 μg/mL; formulation B: 5.78±2.7 μg/mL). Dissolution profiles of the two formulations were similar in the pH 1.2 dissolution medium; however, the dissolution profiles of formulation B were outside the dissolution limit (≥85% at 15 minutes) in the pH 4.5 and 6.8 dissolution media.>Conclusions: No significant changes in the serum concentrations of lamotrigine were seen between the two investigated formulations. There is no evidence to suggest that the differences in dissolution profiles at pH 4.5 and pH 6.8 affect the therapeutic efficacy of the formulations. It is evident that the doses of test formulation given to the patients were higher as a consequence of common assumption that generic products have a lower absorption rate, which is proven unnecessary in this study. This investigation was a pilot study and thus further investigations with a larger sample size are necessary to determine if there is a connection between dissolution profiles and the therapeutic effect of investigated formulations.