Post-marketing assessment of content and efficacy of preservatives in artemisinin-derived antimalarial dry suspensions for paediatric use

BACKGROUND: Artemisinin-derivative formulations are now widely used to treat falciparum malaria. However, the dry powder suspensions developed for children are few and/or are of poor quality. In addition to the active compound, the presence of a suitable preservative in these medicines is essential. In this study, an evaluation of the preservative content and efficacy in some dry suspensions available on the Kenyan market was performed. METHOD: UV spectrophotometry was used to identify the preservatives in each sample while HPLC-UV was used for quantification. After reconstitution of the powders in water, the dissolution of the preservatives was followed for 7 days. Antimicrobial efficacy of the preservatives was assessed by conducting a preservative efficacy test (PET) following the European pharmacopoeia standards. RESULTS: Four different preservatives were identified namely methylparahydroxybenzoate (MP), propylparahydroxybenzoate (PP), benzoic acid and sorbic acid. MP and PP were identified in Artesiane(® )(artemether 300 mg/100 ml), Alaxin(® )(dihydroartemisinin 160 mg/80 ml) andGvither (® )(artemether 300 mg/100 ml) respectively. Sorbic acid was presentin Artenam(® )(artemether 180 mg/60 ml) while benzoic acid was identified in Santecxin(® )(dihydroartemisinin 160 mg/80 ml) andArtexin(® )(dihydroartemisinin 160 mg/80 ml) respectively. Cotecxin(® )(dihydroartemisinin 160 mg/80 ml) did not contain any of the above preservatives. After reconstitution in water, preservativesin 50%(3/6) of the products did not completely dissolve and the PET results revealed that only Artenam(® )and Gvither(® )met the requirements for antimicrobial efficacy. The other products did not conform. CONCLUSION: These results show that paediatric antimalarial dry powder formulations on the market may contain ineffective or incorrect amounts of preservatives. This is a potential risk to the patient. Studies conducted on the dry powder suspensions should include the analysis of both the active ingredient and the preservative, including the efficacy of the latter.