title: 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.
  
  
  METHODS
  Seventy samples of expired FDC-ALU were collected from private pharmacies and malaria researchers in seven African countries. The samples were subjected to thin-layer chromatography (TLC), disintegration testing, and near infrared Raman spectrometry for ascertainment of active ingredients, tablet integrity, and chemical degradation of the tablet formulation including both active ingredients and excipients.
  
  
  RESULTS
  Seventy samples of FDC-ALU were tested in July 2008, between one and 58 months post-expiry. 68 of 70 (97%) samples passed TLC, disintegration and Raman spectrometry testing, including eight samples that were post-expiry by 20 months or longer. A weak linear association (R2 = 0.33) was observed between the age of samples and their state of degradation relative to brand-identical samples on Raman spectrometry. Sixty-eight samples were retested in February 2009 using Raman spectrometry, between eight and 65 months post-expiry. 66 of 68 (97%) samples passed Raman spectrometry retesting. An unexpected observation about African drug logistics was made in three batches of FDC-ALU, which had been sold into the public sector at concessional pricing in accordance with a World Health Organization (WHO) agreement, and which were illegally diverted to the private sector where they were sold for profit.
  
  
  CONCLUSIONS
  The data indicate that FDC-ALU is chemically and physically stable well beyond its stated shelf-life in uncontrolled, tropical conditions. While these data are not themselves sufficient, it is strongly suggested that a re-evaluation of the two-year shelf-life by drug regulatory authorities is warranted.
authors.affiliation: Africa Fighting Malaria, Washington, D.C., USA. RBate@aei.org
authors.forename: Roger
authors.initials: R
authors.lastname: Bate
authors.forename: Richard
authors.initials: R
authors.lastname: Tren
authors.forename: Kimberly
authors.initials: K
authors.lastname: Hess
authors.forename: Amir
authors.initials: A
authors.lastname: Attaran
mesh_terms: D000349:Africa; D000962:Antimalarials / Q000737:chemistry* / Q000592:standards / Q000600:supply & distribution* / Q000627:therapeutic use; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000737:chemistry* / Q000592:standards / Q000600:supply & distribution* / Q000627:therapeutic use; D002855:Chromatography, Thin Layer; D004338:Drug Combinations; D004355:Drug Stability; D004356:Drug Storage; D004983:Ethanolamines / Q000737:chemistry* / Q000592:standards / Q000600:supply & distribution* / Q000627:therapeutic use; D005069:Evaluation Studies as Topic; D005449:Fluorenes / Q000737:chemistry* / Q000592:standards / Q000600:supply & distribution* / Q000627:therapeutic use; D006801:Humans; D019265:Spectroscopy, Near-Infrared; D013607:Tablets; D013997:Time Factors; D014329:Tropical Climate
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D013607:Tablets