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.


METHODS
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) and Artexin (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.


CONCLUSIONS
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.
Atemnkeng
Magnus A
MA
Department of Pharmaceutical Technology and Physical Pharmacy, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. matemnke@vub.ac.be <matemnke@vub.ac.be>
De Cock
Katelijne
K
Plaizier-Vercammen
Jacqueline
J
D000818:Animals; D000900:Anti-Bacterial Agents / Q000032:analysis / Q000494:pharmacology* / Q000592:standards; D000962:Antimalarials / Q000032:analysis*; D037621:Artemisinins / Q000032:analysis*; D002626:Chemistry, Pharmaceutical; D002648:Child; D003257:Consumer Product Safety / Q000592:standards; D004339:Drug Compounding / Q000009:adverse effects / Q000592:standards*; D006801:Humans; D007630:Kenya; D010226:Parabens / Q000032:analysis / Q000494:pharmacology*; D010372:Pediatrics; D010963:Plasmodium falciparum / Q000187:drug effects; D011310:Preservatives, Pharmaceutical / Q000032:analysis / Q000494:pharmacology* / Q000592:standards; D011358:Product Surveillance, Postmarketing / Q000706:statistics & numerical data*
D000900:Anti-Bacterial Agents; D000962:Antimalarials; D037621:Artemisinins; D010226:Parabens; D011310:Preservatives, Pharmaceutical