Experimental designed optimisation and stability evaluation of dry suspensions with artemisinin derivatives for paediatric use

There is a great need for oral anti-malaria preparations especially for small children, which are easy to administer and keep their stability under tropical conditions. The purpose of this work was therefore to develop a dry suspension, containing one of the artemisinin derivatives, namely artesunate, artemether and dihydroartemisinin using fast wetting suspending agents, i.e. xanthan gum and Avicel(R) CL611. For the optimisation of these two variables, namely the suspending agent's content, a Doehlert design was applied. Via preliminary tests on sedimentation behaviour, the limits of both products were determined, respectively 0.1-0.4% (w/v) and 1.0-2.5% (w/v). As responses, sedimentation as a function of time, viscosity and price of the suspension, were evaluated. The stability tests of the reconstituted suspensions showed bad results for artesunate, even when the pH was adapted. In contrast, dihydroartemisinin showed only 10% degradation within 10 days and artemether was stable at least 21 days. Practically the last one was able to foresee a chemically and physically stable suspension at least during the administration period (5 to 7 days) and was therefore selected for further optimisation concerning taste and appearance. Based on the results of selection tests for the colourant, sweetener and taste masking agent, the following composition was proposed for a suitable dry powder with artemether (AM) as active compound to prepare 100 ml reconstituted suspension: AM 300 mg, Avicel(R) CL611 2 g, xanthan gum 200 mg, crystalline saccharose 35 g, citric acid monohydrate 150 mg, Nipagine(R) 80 mg, Nipasol(R) 20 mg, sodium saccharinate 250 mg, tutti-frutti 250 mg and Sunset yellow 10 mg. (C) 2004 Published by Elsevier B.V.