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The initial pharmaceutical development of an artesunate/amodiaquine oral formulation for the treatment of malaria: a public-private partnership
BACKGROUND: Artemisinin-based combination therapy is currently recommended worldwide for the treatment of uncomplicated malaria. Fixed-dose combinations are preferred as they favour compliance. This paper reports on the initial phases of the pharmaceutical development of an artesunate-amodiaquine (A...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128010/ https://www.ncbi.nlm.nih.gov/pubmed/21605361 http://dx.doi.org/10.1186/1475-2875-10-142 |
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author | Lacaze, Catherine Kauss, Tina Kiechel, Jean-René Caminiti, Antonella Fawaz, Fawaz Terrassin, Laurent Cuart, Sylvie Grislain, Luc Navaratnam, Visweswaran Ghezzoul, Bellabes Gaudin, Karen White, Nick J Olliaro, Piero L Millet, Pascal |
author_facet | Lacaze, Catherine Kauss, Tina Kiechel, Jean-René Caminiti, Antonella Fawaz, Fawaz Terrassin, Laurent Cuart, Sylvie Grislain, Luc Navaratnam, Visweswaran Ghezzoul, Bellabes Gaudin, Karen White, Nick J Olliaro, Piero L Millet, Pascal |
author_sort | Lacaze, Catherine |
collection | PubMed |
description | BACKGROUND: Artemisinin-based combination therapy is currently recommended worldwide for the treatment of uncomplicated malaria. Fixed-dose combinations are preferred as they favour compliance. This paper reports on the initial phases of the pharmaceutical development of an artesunate-amodiaquine (ASAQ) bilayer co-formulation tablet, undertaken following pre-formulation studies by a network of scientists and industrials from institutions of both industrialized and low income countries. METHODS: Pharmaceutical development was performed by a research laboratory at the University Bordeaux Segalen, School of Pharmacy, for feasibility and early stability studies of various drug formulations, further transferred to a company specialized in pharmaceutical development, and then provided to another company for clinical batch manufacturing. The work was conducted by a regional public-private not-for-profit network (TropiVal) within a larger Public Private partnership (the FACT project), set up by WHO/TDR, Médecins Sans Frontières and the Drugs for Neglected Disease initiative (DNDi). RESULTS: The main pharmaceutical goal was to combine in a solid oral form two incompatible active principles while preventing artesunate degradation under tropical conditions. Several options were attempted and failed to provide satisfactory stability results: incorporating artesunate in the external phase of the tablets, adding a pH regulator, alcoholic wet granulation, dry granulation, addition of an hydrophobic agent, tablet manufacturing in controlled conditions. However, long-term stability could be achieved, in experimental batches under GMP conditions, by physical separation of artesunate and amodiaquine in a bilayer co-formulation tablet in alu-alu blisters. Conduction of the workplan was monitored by DNDi. CONCLUSIONS: Collaborations between research and industrial groups greatly accelerated the process of development of the bi-layered ASAQ tablet. Lack of public funding was the main obstacle hampering the development process, and no intellectual property right was claimed. This approach resulted in a rapid technology transfer to the drug company Sanofi-Aventis, finalizing the process of development, registration and WHO pre-qualification of the fixed-dose co-formulation together with DNDi. The bi-layered tablet is made available under the names of Coarsucam(® )and Artesunate amodiaquine Winthrop(®), Sanofi-Aventis. The issue related to the difficulty of public institutions to valorise their participation in such initiative by lack of priority and funding of applied research is discussed. |
format | Online Article Text |
id | pubmed-3128010 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-31280102011-07-01 The initial pharmaceutical development of an artesunate/amodiaquine oral formulation for the treatment of malaria: a public-private partnership Lacaze, Catherine Kauss, Tina Kiechel, Jean-René Caminiti, Antonella Fawaz, Fawaz Terrassin, Laurent Cuart, Sylvie Grislain, Luc Navaratnam, Visweswaran Ghezzoul, Bellabes Gaudin, Karen White, Nick J Olliaro, Piero L Millet, Pascal Malar J Research BACKGROUND: Artemisinin-based combination therapy is currently recommended worldwide for the treatment of uncomplicated malaria. Fixed-dose combinations are preferred as they favour compliance. This paper reports on the initial phases of the pharmaceutical development of an artesunate-amodiaquine (ASAQ) bilayer co-formulation tablet, undertaken following pre-formulation studies by a network of scientists and industrials from institutions of both industrialized and low income countries. METHODS: Pharmaceutical development was performed by a research laboratory at the University Bordeaux Segalen, School of Pharmacy, for feasibility and early stability studies of various drug formulations, further transferred to a company specialized in pharmaceutical development, and then provided to another company for clinical batch manufacturing. The work was conducted by a regional public-private not-for-profit network (TropiVal) within a larger Public Private partnership (the FACT project), set up by WHO/TDR, Médecins Sans Frontières and the Drugs for Neglected Disease initiative (DNDi). RESULTS: The main pharmaceutical goal was to combine in a solid oral form two incompatible active principles while preventing artesunate degradation under tropical conditions. Several options were attempted and failed to provide satisfactory stability results: incorporating artesunate in the external phase of the tablets, adding a pH regulator, alcoholic wet granulation, dry granulation, addition of an hydrophobic agent, tablet manufacturing in controlled conditions. However, long-term stability could be achieved, in experimental batches under GMP conditions, by physical separation of artesunate and amodiaquine in a bilayer co-formulation tablet in alu-alu blisters. Conduction of the workplan was monitored by DNDi. CONCLUSIONS: Collaborations between research and industrial groups greatly accelerated the process of development of the bi-layered ASAQ tablet. Lack of public funding was the main obstacle hampering the development process, and no intellectual property right was claimed. This approach resulted in a rapid technology transfer to the drug company Sanofi-Aventis, finalizing the process of development, registration and WHO pre-qualification of the fixed-dose co-formulation together with DNDi. The bi-layered tablet is made available under the names of Coarsucam(® )and Artesunate amodiaquine Winthrop(®), Sanofi-Aventis. The issue related to the difficulty of public institutions to valorise their participation in such initiative by lack of priority and funding of applied research is discussed. BioMed Central 2011-05-23 /pmc/articles/PMC3128010/ /pubmed/21605361 http://dx.doi.org/10.1186/1475-2875-10-142 Text en Copyright ©2011 Lacaze et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Lacaze, Catherine Kauss, Tina Kiechel, Jean-René Caminiti, Antonella Fawaz, Fawaz Terrassin, Laurent Cuart, Sylvie Grislain, Luc Navaratnam, Visweswaran Ghezzoul, Bellabes Gaudin, Karen White, Nick J Olliaro, Piero L Millet, Pascal The initial pharmaceutical development of an artesunate/amodiaquine oral formulation for the treatment of malaria: a public-private partnership |
title | The initial pharmaceutical development of an artesunate/amodiaquine oral formulation for the treatment of malaria: a public-private partnership |
title_full | The initial pharmaceutical development of an artesunate/amodiaquine oral formulation for the treatment of malaria: a public-private partnership |
title_fullStr | The initial pharmaceutical development of an artesunate/amodiaquine oral formulation for the treatment of malaria: a public-private partnership |
title_full_unstemmed | The initial pharmaceutical development of an artesunate/amodiaquine oral formulation for the treatment of malaria: a public-private partnership |
title_short | The initial pharmaceutical development of an artesunate/amodiaquine oral formulation for the treatment of malaria: a public-private partnership |
title_sort | initial pharmaceutical development of an artesunate/amodiaquine oral formulation for the treatment of malaria: a public-private partnership |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128010/ https://www.ncbi.nlm.nih.gov/pubmed/21605361 http://dx.doi.org/10.1186/1475-2875-10-142 |
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