Physical and chemical stability of expired fixed dose combination artemether-lumefantrine in uncontrolled tropical conditions

Abstract

Background: New artemisinin combination therapies pose difficulties of implementation in developing and tropical settings because they have a short shelf-life (two years) relative to the medicines they replace. This limits the reliability and cost of treatment, and the acceptability of this treatment to health care workers. A multi-pronged investigation was made into the chemical and physical stability of fixed dose combination artemether-lumefantrine (FDC-ALU) stored under heterogeneous, uncontrolled African conditions, to probe if a shelf-life extension might be possible.

Degradation Study on the Effects of Storage Conditions on Active Ingredient of an ACT- Based Anti-malarial Drugs

“…Statistical analysis proved that the method is repeatable and selective for the analysis of artemether as bulk drug and in pharmaceutical formulations. Our findings is consistent with the results of Bate et al [25] who found that though artemetherlumefantrine has passed its labelled expiry date with about 3months, their concentration was stable and not degraded and also agrees with Arun and Smith [26] who developed and validated a HPLC-UV method for the simultaneous estimation of artemether and lumefantrine in fixed-dose combination tablets. In their study, HPLC analyses were carried out with a coupled UV detector.…”

Artemether–lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria

“…Most recent data indicate that AL tablets may be chemically and physically stable well beyond the stated shelf-life even under tropical, ie, warm, conditions 44. These data should, however, not pave the way for a permissive attitude about the stability of AL tablets, but rather lead to thorough investigation and examinations and, if possible, chemical and galenic improvement.…”

Quality and stability of artemether-lumefantrine stored under ambient conditions in rural Mali

“…Drug quality and stability in the developing world is a serious concern. Although there have been some studies of artemisinin quality and stability [ 9 – 11 ], this study appears to be the first peer-reviewed study to both evaluate the products’ quality and then study its stability under ambient tropical conditions. The study products were also compared to a reference product.…”

“…Analysis by MS and NMR revealed an artesunate degradation product that was virtually undetectable in the non heat-stressed samples. Bate et al obtained samples of artemether-lumefantrine that were 1 – 58 months past their labelled expiry date [ 11 ]. They found that 97% of expired products passed tests for tablet integrity and the presence and amount of active ingredients using thin layer chromatography, tablet disintegration and infrared (IR) spectroscopy but they did not study the samples using dissolution testing.…”