Dissolution testing of bilayer tablets: Method development, validation and application in post-marketing quality evaluation

Abstract

Bilayer tablets are gaining importance as they provide a multilayer system for administration of incompatible or synergistic drugs and reduce the dosing unit burden. Furthermore, two different APIs or portions of an API with different release characteristics can be formulated as single unit, having different layers. Most of the research is directed towards physical stability (prevention of delamination), and simultaneous dissolution testing of different APIs in bilayer tablets has been neglected. In the present study, a method was developed for simultaneous determination of dissolution rates of clopidogrel and aspirin from bilayer tablets. Dissolution media was selected on the basis of sink conditions for both the drugs. Various experimental conditions (type of apparatus, agitation rate, and volume of dissolution media) were optimized, and the developed method was validated according to USP and ICH guidelines. Analysis of dissolution samples was carried out by HPLC using an ODS C-18 column (250 x 4.6 mm, 5 μm) as the stationary phase. The mobile phase consisted of a combination of acetonitrile, methanol, and phosphate buffer (50:7:43, v/v/v) pumped at flow rate of 2 mL/min at ambient temperature while the detector wavelength was set at 240 nm. An independent model approach was applied for comparison of dissolution profiles. The best in vitro dissolution profiles were obtained using 900 mL of hydrochloric acid (HCl) buffer (pH 3) as dissolution media held at 37 ± 2°C and stirred at 75 rpm using apparatus- II. Complete dissolution was achieved within 45 min. for both the drugs. Validation parameters revealed accuracy, precision, and robustness of the method without any interference with sample analysis. The developed method will be helpful in dissolution testing of bilayer tablets containing clopidogrel and aspirin at the level of product development and during routine quality control analysis and post-marketing surveillance studies.