Preliminary formulation of a fixed-dose paediatric combination of artesunate and amodiaquine hydrochloride

Background. Since the introduction of artemisinin combination therapy (ACT), it has been recognised that challenges exist in presenting drugs as fixed dose combinations due to potential incompatibilities of the different chemical compounds. The aim of this study was to develop stable prototype formulations combining Artesunate (ART) and Amodiaquine hydrochloride (AMQ). Materials and Methods. Two fast-disintegrating granular formulations, containing ART and AMQ respectively were produced by wet granulation. Samples were stored as single component formulations or blends in glass vials for periods up to 13 weeks at refrigerated storage conditions (10C), room temperature (24-26C) and ambient humidity (in the dark and light conditions), 25C/75% RH, and 50C/75% RH. The active agent content of the two drugs was determined using HPLC-UV at 1, 4 and 13 weeks from the start of the study. Statistical analysis of data were undertaken to determine the factors influencing the stability of the formulations, both alone and in combination. Results. The chemical stability of ART was markedly affected by relative humidity, with greatest levels of degradation occurring at 13 weeks after storage at 50C/75% RH. No significant loss of active agent content was observed for AMQ at any storage conditions over the duration of the study. Conclusions. The results indicate that stable fixed dose granular formulations of ART and AMQ can be produced that are stable under accelerated conditions. These formulations should, however, be protected from extremes of relative humidity using suitable packaging materials to avoid degradation of ART.