Physical and Chemical Stability of Expired Fixed Dose Combination Artemether-Lumefantrine in Uncontrolled Tropical Conditions

Malaria Journal, Vol. 8, No. 33, pp. 1-7, February 2009

8 Pages Posted: 6 Mar 2010 Last revised: 17 Oct 2013

See all articles by Roger Bate

Roger Bate

American Enterprise Institute (AEI)

Richard Tren

Africa Fighting Malaria (US)

Kimberly Hess

Africa Fighting Malaria (US)

Amir Attaran

University of Ottawa - Department of Epidemiology and Community Medicine; University of Ottawa - Common Law Section

Date Written: February 25, 2009

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.

Conclusion: 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.

Suggested Citation

Bate, Roger and Tren, Richard and Hess, Kimberly and Attaran, Amir, Physical and Chemical Stability of Expired Fixed Dose Combination Artemether-Lumefantrine in Uncontrolled Tropical Conditions (February 25, 2009). Malaria Journal, Vol. 8, No. 33, pp. 1-7, February 2009, Available at SSRN: https://ssrn.com/abstract=1565599

Roger Bate

American Enterprise Institute (AEI) ( email )

1150 17th Street, N.W.
Washington, DC 20036
United States

Richard Tren

Africa Fighting Malaria (US) ( email )

Washington, DC
United States

Kimberly Hess

Africa Fighting Malaria (US) ( email )

Washington, DC
United States

Amir Attaran (Contact Author)

University of Ottawa - Department of Epidemiology and Community Medicine ( email )

451 Smyth Road
Ottawa, Ontario K1H 8M5
Canada

University of Ottawa - Common Law Section ( email )

57 Louis Pasteur Street
Ottawa, K1N 6N5
Canada
613-562-5800 ext: 2015 (Phone)
613-562-5659 (Fax)

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