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Development of a dissolution method for lumefantrine and artemether in immediate release fixed dose artemether/lumefantrine tablets

BACKGROUND: Dissolution of artemether (ART) and lumefantrine (LUM) active pharmaceutical ingredients (APIs) in fixed dose combination (FDC) ART/LUM tablets is one of the critical quality attributes. Thus, the verification of the release profile of ART and LUM from FDC ART/LUM tablets using a robust...

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Autores principales: Belew, Sileshi, Suleman, Sultan, Duguma, Markos, Teshome, Henok, Wynendaele, Evelien, Duchateau, Luc, De Spiegeleer, Bart
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140584/
https://www.ncbi.nlm.nih.gov/pubmed/32264882
http://dx.doi.org/10.1186/s12936-020-03209-5
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author Belew, Sileshi
Suleman, Sultan
Duguma, Markos
Teshome, Henok
Wynendaele, Evelien
Duchateau, Luc
De Spiegeleer, Bart
author_facet Belew, Sileshi
Suleman, Sultan
Duguma, Markos
Teshome, Henok
Wynendaele, Evelien
Duchateau, Luc
De Spiegeleer, Bart
author_sort Belew, Sileshi
collection PubMed
description BACKGROUND: Dissolution of artemether (ART) and lumefantrine (LUM) active pharmaceutical ingredients (APIs) in fixed dose combination (FDC) ART/LUM tablets is one of the critical quality attributes. Thus, the verification of the release profile of ART and LUM from FDC ART/LUM tablets using a robust and discriminatory dissolution method is crucial. Therefore, the aim of this study was to develop and validate an appropriate dissolution method for quality control of FDC ART/LUM tablets. METHODS: The dissolution medium was selected based on saturation solubility data and sink conditions. The effect of agitation speed, pH and surfactant concentration on the release of ART and LUM was evaluated by employing a two-level factorial experiment. The resulting final method was validated for linearity, precision, robustness and API stability. In addition, the discriminatory power of the method was evaluated using expired and unexpired FDC ART/LUM products. RESULTS: A suitable dissolution profile of FDC ART/LUM tablets was obtained in 900 ml HCl (0.025 N, pH 1.6) with 1%Myrj 52 using paddle method at 100 rpm and 37 °C. ART and LUM were analysed using a HPLC method with UV detection at wavelengths of 210 and 335 nm, respectively. The results from the stability study showed that ART and LUM were sufficiently stable in HCl (0.025 N, pH 1.6) with 1%Myrj 52 at 37 °C. The method was linear (r(2) = 0.999) over the concentration range of 6.25–100 μg/ml. The results for precision were within the acceptance limit (%RSD < 2). The percent relative standard deviation (< 2%) and statistically non-significant (p > 0.05) difference in release of ART and LUM observed between deliberately changed dissolution method settings (pH = 1.6 ± 0.2 or agitation speed = 100 ± 2) and optimized dissolution conditions revealed the robustness of the dissolution method. The method was capable to discriminate among different FDC ART/LUM products with different quality. CONCLUSIONS: The developed dissolution method is robust and discriminatory. It can be used in the quality evaluation of FDC ART/LUM tablets.
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spelling pubmed-71405842020-04-14 Development of a dissolution method for lumefantrine and artemether in immediate release fixed dose artemether/lumefantrine tablets Belew, Sileshi Suleman, Sultan Duguma, Markos Teshome, Henok Wynendaele, Evelien Duchateau, Luc De Spiegeleer, Bart Malar J Research BACKGROUND: Dissolution of artemether (ART) and lumefantrine (LUM) active pharmaceutical ingredients (APIs) in fixed dose combination (FDC) ART/LUM tablets is one of the critical quality attributes. Thus, the verification of the release profile of ART and LUM from FDC ART/LUM tablets using a robust and discriminatory dissolution method is crucial. Therefore, the aim of this study was to develop and validate an appropriate dissolution method for quality control of FDC ART/LUM tablets. METHODS: The dissolution medium was selected based on saturation solubility data and sink conditions. The effect of agitation speed, pH and surfactant concentration on the release of ART and LUM was evaluated by employing a two-level factorial experiment. The resulting final method was validated for linearity, precision, robustness and API stability. In addition, the discriminatory power of the method was evaluated using expired and unexpired FDC ART/LUM products. RESULTS: A suitable dissolution profile of FDC ART/LUM tablets was obtained in 900 ml HCl (0.025 N, pH 1.6) with 1%Myrj 52 using paddle method at 100 rpm and 37 °C. ART and LUM were analysed using a HPLC method with UV detection at wavelengths of 210 and 335 nm, respectively. The results from the stability study showed that ART and LUM were sufficiently stable in HCl (0.025 N, pH 1.6) with 1%Myrj 52 at 37 °C. The method was linear (r(2) = 0.999) over the concentration range of 6.25–100 μg/ml. The results for precision were within the acceptance limit (%RSD < 2). The percent relative standard deviation (< 2%) and statistically non-significant (p > 0.05) difference in release of ART and LUM observed between deliberately changed dissolution method settings (pH = 1.6 ± 0.2 or agitation speed = 100 ± 2) and optimized dissolution conditions revealed the robustness of the dissolution method. The method was capable to discriminate among different FDC ART/LUM products with different quality. CONCLUSIONS: The developed dissolution method is robust and discriminatory. It can be used in the quality evaluation of FDC ART/LUM tablets. BioMed Central 2020-04-07 /pmc/articles/PMC7140584/ /pubmed/32264882 http://dx.doi.org/10.1186/s12936-020-03209-5 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Belew, Sileshi
Suleman, Sultan
Duguma, Markos
Teshome, Henok
Wynendaele, Evelien
Duchateau, Luc
De Spiegeleer, Bart
Development of a dissolution method for lumefantrine and artemether in immediate release fixed dose artemether/lumefantrine tablets
title Development of a dissolution method for lumefantrine and artemether in immediate release fixed dose artemether/lumefantrine tablets
title_full Development of a dissolution method for lumefantrine and artemether in immediate release fixed dose artemether/lumefantrine tablets
title_fullStr Development of a dissolution method for lumefantrine and artemether in immediate release fixed dose artemether/lumefantrine tablets
title_full_unstemmed Development of a dissolution method for lumefantrine and artemether in immediate release fixed dose artemether/lumefantrine tablets
title_short Development of a dissolution method for lumefantrine and artemether in immediate release fixed dose artemether/lumefantrine tablets
title_sort development of a dissolution method for lumefantrine and artemether in immediate release fixed dose artemether/lumefantrine tablets
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140584/
https://www.ncbi.nlm.nih.gov/pubmed/32264882
http://dx.doi.org/10.1186/s12936-020-03209-5
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