A flow-through dissolution method for a two component drug formulation where the actives have markedly differing solubility properties

A flow-through dissolution method has been developed for the routine testing of an anti-malarial tablet formulation containing two actives having markedly differing solubility properties. The flow-through apparatus was used because the dissolution rate of one of the components in the selected dissolution fluid using the EP/USP paddle apparatus was found to be poor. This was found to result from the formation of non-sink conditions caused by the presence of the other component in the formulation. We describe a test in which the component shown to exert the adverse affect is removed prior to measuring the dissolution rate of the affected component. This was achieved by taking advantage of the markedly differing solubility properties of each component in different dissolution fluids (water and 0.1 M sodium hydroxide). After a specified time in the test, the dissolution fluid is switched from water to sodium hydroxide to allow the dissolution of the affected component to occur. The results obtained were found to be satisfactory with dissolution rates of over 90% obtained. The effect of flow rate and sodium hydroxide concentration was investigated. The results showed that both factors had a significant effect on the dissolution rate of the component of interest. (C) 1998 Elsevier Science B.V. All rights reserved.