The artemisinin-derivatives, artemether, artesunate, arteether and dihydroartemisinin, are currently the most potent antimalarial medicines on the market. They are widely available in the different pharmaceutical dosage forms including tablets, injections, suppositories and dry powders .
Since artemisinin and its derivatives are poorly water-soluble and are not very stable in solution, the preparations have to be formulated in the dry form for subsequent reconstitution into a wet suspension with water just before use. The dry powders for reconstitution are normally designed for children from 0–5 years of age, who are not able to swallow tablets. In the malaria endemic countries, living conditions are often poor, including scarce access to clean portable drinking water . As a result, microorganisms can easily thrive when the dry powder is reconstituted with poor quality water. In addition, children suffering from malaria, as well as AIDS or typhoid, have a weakened immunological system and are, therefore, more susceptible to other infections. Moreover, the drugs are packaged in multiple dose containers, making the preparation highly susceptible to contamination following frequent use. Hence, pharmaceutical preparations which need an aqueous vehicle such as syrups and powders for oral suspensions require safeguards from microbial contamination, which may affect product stability or infect the consumer. This is accomplished by the addition of antimicrobial agents in the formulation to destroy and inhibit the growth of those organisms that may contaminate the product during manufacture or use .
The International Committee on Harmonization (ICH) guidelines  requests that for submission of drug registration dossier on dry powders for oral suspensions, data should be provided for the content of the active pharmaceutical ingredient (API) as well as the type(s) and amount(s) of the preservative(s) used. In addition, the efficacy of the antimicrobial preservation should be demonstrated by challenging the reconstituted suspension in its final container with specified microorganisms. This implies that the preservative used in the dry powder must completely dissolve on addition of water to impart the preservation action.
Sources of this microbial contamination may include air and water, manufacturing equipment, manufacturing personnel and/or the consumer . Bacterial contamination of products through consumer use, has resulted in presence of mixed and harmful microbial flora in the product .
Major studies on antimalarial formulations are limited to the active ingredients without mention of the preservatives when studied in syrups and dry powders. In view of the biological role that this excipient plays towards the maintenance of the preparation and the recovery of the patient, there is a dire need for greater attention and awareness directed towards the importance of preservation in paediatric formulations.
Several chemical preservative agents exist and have been widely employed in the cosmetic, food and pharmaceutical industries . For oral use, the choices of the preservatives are limited. These include benzoic acid (BA) C6H5COOH and sorbic acid (SA) C5H7COOH, which are generally effective to control mould and yeast growth, and the parahydroxybenzoic acid esters: methylparaben (MP) C6H4(OH)COOCH3 and propylparaben (PP) C6H4(OH)COOC3H7, which are most commonly used to control bacterial growth due to their broad antimicrobial spectrum with good stability and non-volatility . MP and PP are usually used in combination as they possess a synergistic activity when used together. However, overuse of preservatives may cause allergic reactions hence, they should be shown not to be cytotoxic or sensitizing [8, 9].
Recently, the artemisinin-derivative drugs have become a major target for counterfeiters. Fake and substandard versions of original brands have previously been reported in Southeast Asia [10, 11] and now in Africa . The substandard copies were present in all dosage forms but most especially in the tablets and dry powders. In the latter, quality analysis should also be performed on the preservatives. No report has been published on efficacy of preservatives in artemisinin-like antimalarial drugs.
Thus, the aim of this study was (1) to identify the commonly used antimicrobial agents in the artemisinin-containing dry suspensions on the market, (2) study the dissolution profiles of these preservatives after reconstituting in water, (3) evaluate the activity of the preservatives by performing the preservative efficacy test (PET) on the wet suspension and (4) describe some simple analytical procedures for these analytes in dry powders. The different high performance liquid chromatography (HPLC) methods used were validated for each analyte.