title: Fixed artesunate-amodiaquine combined pre-formulation study for the treatment of malaria.
abstract: 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.
authors.affiliation: Laboratory of Galenic Pharmacy and Biopharmacy, Bordeaux 2 University, France.
authors.forename: Tina
authors.initials: T
authors.lastname: Kauss
authors.forename: Fawaz
authors.initials: F
authors.lastname: Fawaz
authors.forename: Michel
authors.initials: M
authors.lastname: Guyot
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Lagueny
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dos Santos
authors.forename: François
authors.initials: F
authors.lastname: Bonini
authors.forename: Piero
authors.initials: P
authors.lastname: Olliaro
authors.forename: Antonella
authors.initials: A
authors.lastname: Caminiti
authors.forename: Pascal
authors.initials: P
authors.lastname: Millet