Physical and chemical stability of expired fixed dose combination artemether-lumefantrine in uncontrolled tropical conditions
<p>Abstract</p> <p>Background</p> <p>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 co...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2009-02-01
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| Series: | Malaria Journal |
| Online Access: | http://www.malariajournal.com/content/8/1/33 |
| _version_ | 1818758613673443328 |
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| author | Hess Kimberly Tren Richard Bate Roger Attaran Amir |
| author_facet | Hess Kimberly Tren Richard Bate Roger Attaran Amir |
| author_sort | Hess Kimberly |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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 (R<sup>2 </sup>= 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.</p> <p>Conclusion</p> <p>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.</p> |
| first_indexed | 2024-12-18T06:29:37Z |
| format | Article |
| id | doaj.art-4629de8eef324e9a8291374a80de6f66 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-18T06:29:37Z |
| publishDate | 2009-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-4629de8eef324e9a8291374a80de6f662022-12-21T21:17:57ZengBMCMalaria Journal1475-28752009-02-01813310.1186/1475-2875-8-33Physical and chemical stability of expired fixed dose combination artemether-lumefantrine in uncontrolled tropical conditionsHess KimberlyTren RichardBate RogerAttaran Amir<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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 (R<sup>2 </sup>= 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.</p> <p>Conclusion</p> <p>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.</p>http://www.malariajournal.com/content/8/1/33 |
| spellingShingle | Hess Kimberly Tren Richard Bate Roger Attaran Amir Physical and chemical stability of expired fixed dose combination artemether-lumefantrine in uncontrolled tropical conditions Malaria Journal |
| title | Physical and chemical stability of expired fixed dose combination artemether-lumefantrine in uncontrolled tropical conditions |
| title_full | Physical and chemical stability of expired fixed dose combination artemether-lumefantrine in uncontrolled tropical conditions |
| title_fullStr | Physical and chemical stability of expired fixed dose combination artemether-lumefantrine in uncontrolled tropical conditions |
| title_full_unstemmed | Physical and chemical stability of expired fixed dose combination artemether-lumefantrine in uncontrolled tropical conditions |
| title_short | Physical and chemical stability of expired fixed dose combination artemether-lumefantrine in uncontrolled tropical conditions |
| title_sort | physical and chemical stability of expired fixed dose combination artemether lumefantrine in uncontrolled tropical conditions |
| url | http://www.malariajournal.com/content/8/1/33 |
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