Development and Validation of a Dissolution Test Method for Artemether and Lumefantrine in Tablets
Purpose: To develop and validate a dissolution test method for dissolution release of artemether and lumefantrine from tablets.
Methods: A single dissolution method for evaluating the in vitro release of artemether and lumefantrine from tablets was developed and validated. The method comprised of a dissolution medium of 1000 ml of 2 %w/v of Myrj 52 in 0.005M HCl per vessel with the paddle rotating at 100 rpm for 120 min. The dissolution samples were analysed using a Waters HPLC system with Waters symmetry column (C-18 column of 250mm x 4.6mm i.d., 5 μ particle size). The mobile phase was a mixture of 20 volumes of 0.5 %v/v of triethylamine in water (adjusted to a pH of 3.0 with orthophosphoric acid) and 80 volumes of acetonitrile. The detection wavelength was set at 216 nm and 100 μl of each sample was injected. The HPLC method used for the determination of drug release was validated for the parameters of accuracy, precision, linearity, specificity, filter validation, solution stability and robustness.
Results: The dissolution test provided sink conditions for artemether and lumefantrine and was able to discriminate between tablet formulations of different hardness and different composition. Application of Mann-Whitney U test for significant difference between samples at various time points during the dissolution test yielded z values > 1.96 (1.96 = critical z value at p = 0.05) for the various formulations tested, indicating the discriminatory power of the dissolution test.
Conclusion: This validated dissolution test may be used as a single dissolution test for artemether and luminfantrine in tablet formulations.
Keywords: Artemether, Lumefantrine, Tablet formulations, Single dissolution test, HPLC