Original Articles
M. EL Karbane, Y. Ramli, M. Am
Abstract
The UV-Vis method required by the USP pharmacopeia for simvastatin tablet dissolution assays suffers from a lack of specificity and reproducibility which limit its use to perform kinetic dissolution profile between the innovator and its generics. This variability caused by the manganese dioxide treatment step or by the hydrolysed compound of simvastatin. In order to obtain an acceptable precision of the percent release of simvastatin under normal and accelerated conditions, a HPLC method was developed and validated according to ICH Q2R1 guidelines. The separation was achieved using a GL Science Inertsil ODS - 3 V (5μm, 150mm×4.6mm i.d.) column. The gradient elution mobile phase was composed of buffer (pH=4.2, 12 mM sodium acetate and adjust pH by glacial acetic acid and acetonitrile at a flow rate of 1.7ml/min. The detection was performed at 238 nm. It was demonstrated that the USP UV-Vis method is not suitable to assess the dissolution kinetic profiles and to perform a comparative study between the innovator and different references of simvastatin. This UV-visible method cannot distinguish between the simvastatin as principal active ingredient and its impurity A obtained by hydrolysis in the dissolution medium test. While it was demonstrated that the HPLC method is more suitable to quantify accurately and precisely the percent release of the innovator and the generics for simvastatin under normal and accelerated conditions