Isoniazid, pyrazinamide and rifampicin content variation in split fixed-dose combination tablets

Setting: In most developing countries, paediatric tuberculosis is treated with split tablets leading to potential inaccuracy in the dose delivery and drug exposure. There is no data on the quality of first-line drugs content in split fixed-dose combination tablets. Objective: To determine Isoniazid,...

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Main Authors: Thomas Pouplin, Pham Nguyen Phuong, Pham Van Toi, Julie Nguyen Pouplin, Jeremy Farrar
Other Authors: Mahidol University
Format: Article
Published: 2018
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Online Access:https://repository.li.mahidol.ac.th/handle/123456789/33006
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spelling th-mahidol.330062018-11-09T09:35:57Z Isoniazid, pyrazinamide and rifampicin content variation in split fixed-dose combination tablets Thomas Pouplin Pham Nguyen Phuong Pham Van Toi Julie Nguyen Pouplin Jeremy Farrar Mahidol University Oxford University Clinical Research Unit Nuffield Department of Clinical Medicine Agricultural and Biological Sciences Biochemistry, Genetics and Molecular Biology Medicine Setting: In most developing countries, paediatric tuberculosis is treated with split tablets leading to potential inaccuracy in the dose delivery and drug exposure. There is no data on the quality of first-line drugs content in split fixed-dose combination tablets. Objective: To determine Isoniazid, Pyrazinamide and Rifampicin content uniformity in split FDC tablets used in the treatment of childhood tuberculosis. Design: Drug contents of 15 whole tablets, 30 half tablets and 36 third tablets were analysed by high performance liquid chromatography. The content uniformity was assessed by comparing drug content measured in split portions with their expected amounts and the quality of split portions was assessed applying qualitative specifications for whole tablets. Results: All whole tablets measurements fell into the USP proxy for the three drugs. But a significant number of half and third portions was found outside the tolerated variation range and the split formulation failed the requirements for content uniformity. To correct for the inaccuracy of splitting the tablets into equal portions, a weight-adjustment strategy was used but this did not improve the findings. Conclusion: In split tablets the content of the three drugs is non-uniform and exceeded the USP recommendations. There is an absolute need to make child-friendly formulations available for the treatment of childhood tuberculosis. © 2014 Pouplin et al. 2018-11-09T01:44:22Z 2018-11-09T01:44:22Z 2014-07-08 Article PLoS ONE. Vol.9, No.7 (2014) 10.1371/journal.pone.0102047 19326203 2-s2.0-84903881870 https://repository.li.mahidol.ac.th/handle/123456789/33006 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84903881870&origin=inward
institution Mahidol University
building Mahidol University Library
continent Asia
country Thailand
Thailand
content_provider Mahidol University Library
collection Mahidol University Institutional Repository
topic Agricultural and Biological Sciences
Biochemistry, Genetics and Molecular Biology
Medicine
spellingShingle Agricultural and Biological Sciences
Biochemistry, Genetics and Molecular Biology
Medicine
Thomas Pouplin
Pham Nguyen Phuong
Pham Van Toi
Julie Nguyen Pouplin
Jeremy Farrar
Isoniazid, pyrazinamide and rifampicin content variation in split fixed-dose combination tablets
description Setting: In most developing countries, paediatric tuberculosis is treated with split tablets leading to potential inaccuracy in the dose delivery and drug exposure. There is no data on the quality of first-line drugs content in split fixed-dose combination tablets. Objective: To determine Isoniazid, Pyrazinamide and Rifampicin content uniformity in split FDC tablets used in the treatment of childhood tuberculosis. Design: Drug contents of 15 whole tablets, 30 half tablets and 36 third tablets were analysed by high performance liquid chromatography. The content uniformity was assessed by comparing drug content measured in split portions with their expected amounts and the quality of split portions was assessed applying qualitative specifications for whole tablets. Results: All whole tablets measurements fell into the USP proxy for the three drugs. But a significant number of half and third portions was found outside the tolerated variation range and the split formulation failed the requirements for content uniformity. To correct for the inaccuracy of splitting the tablets into equal portions, a weight-adjustment strategy was used but this did not improve the findings. Conclusion: In split tablets the content of the three drugs is non-uniform and exceeded the USP recommendations. There is an absolute need to make child-friendly formulations available for the treatment of childhood tuberculosis. © 2014 Pouplin et al.
author2 Mahidol University
author_facet Mahidol University
Thomas Pouplin
Pham Nguyen Phuong
Pham Van Toi
Julie Nguyen Pouplin
Jeremy Farrar
format Article
author Thomas Pouplin
Pham Nguyen Phuong
Pham Van Toi
Julie Nguyen Pouplin
Jeremy Farrar
author_sort Thomas Pouplin
title Isoniazid, pyrazinamide and rifampicin content variation in split fixed-dose combination tablets
title_short Isoniazid, pyrazinamide and rifampicin content variation in split fixed-dose combination tablets
title_full Isoniazid, pyrazinamide and rifampicin content variation in split fixed-dose combination tablets
title_fullStr Isoniazid, pyrazinamide and rifampicin content variation in split fixed-dose combination tablets
title_full_unstemmed Isoniazid, pyrazinamide and rifampicin content variation in split fixed-dose combination tablets
title_sort isoniazid, pyrazinamide and rifampicin content variation in split fixed-dose combination tablets
publishDate 2018
url https://repository.li.mahidol.ac.th/handle/123456789/33006
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