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Artemisinin-based combination therapies, including artesunate (AS) + amodiaquine (AQ), are the currently recommended first-line treatment of uncomplicated falciparum malaria. Fixed-dose co-formulations offer logistic and adherence advantages. This paper reports the initial research phase of the pre-development process of an AS-AQ formulation, further developed by the Drug for Neglected Diseases Initiative (DNDi). Results demonstrate that AS and AQ are not compatible, and AS degradation is related to three main parameters: water content (>1%), elevated temperature (80 degrees C in dry condition) and possibly the 4-aminoquinoline moiety. Furthermore, AS and AQ incompatibility led to AS degradation and pharmaco-technical changes in classical wet granulation tablets. Both active principles are stable as dry powders. These investigations led to further development of various co-formulations, including the bilayer tablet currently on the market.

Original publication

DOI

10.1016/j.ijpharm.2010.05.038

Type

Journal article

Journal

International journal of pharmaceutics

Publication Date

08/2010

Volume

395

Pages

198 - 204

Addresses

Laboratory of Galenic Pharmacy and Biopharmacy, Bordeaux 2 University, France. tina.kauss@u-bordeaux2.fr

Keywords

Malaria, Falciparum, Water, Ethanol, Artemisinins, Amodiaquine, Powders, Tablets, Drug Combinations, Antimalarials, Solvents, Feasibility Studies, Drug Compounding, Drug Stability, Humidity, Kinetics, Chemistry, Pharmaceutical, Hydrogen-Ion Concentration, Solubility, Hot Temperature