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Impact of Excipients and Seeding on the Solid-State Form Transformation of Indomethacin during Liquid Antisolvent Precipitation
[Image: see text] Long-acting injectables are a unique drug formulation strategy, providing a slow and sustained release of active pharmaceutical ingredients (APIs). In this study, a novel approach that combines liquid antisolvent precipitation with seeding to obtain a stable form of the API indomet...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9542716/ https://www.ncbi.nlm.nih.gov/pubmed/36217420 http://dx.doi.org/10.1021/acs.cgd.2c00678 |
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author | Hugo Silva, Mariana Kumar, Ajay Hodnett, Benjamin K. Tajber, Lidia Holm, René Hudson, Sarah P. |
author_facet | Hugo Silva, Mariana Kumar, Ajay Hodnett, Benjamin K. Tajber, Lidia Holm, René Hudson, Sarah P. |
author_sort | Hugo Silva, Mariana |
collection | PubMed |
description | [Image: see text] Long-acting injectables are a unique drug formulation strategy, providing a slow and sustained release of active pharmaceutical ingredients (APIs). In this study, a novel approach that combines liquid antisolvent precipitation with seeding to obtain a stable form of the API indomethacin while achieving the desired particle size distribution is described. It was proven that when a metastable form of indomethacin was initially nucleated, the rate of its transformation to the stable form was influenced by the presence of excipients and seeds (17.10 ± 0.20 μm), decreasing from 48 to 4 h. The final particle size (D50) of the indomethacin suspension produced without seeding was 7.33 ± 0.38 μm, and with seeding, it was 5.61 ± 0.14 μm. Additionally, it was shown that the particle size distribution of the seeds and the time point of seed addition were critical to obtain the desired solid-state form and that excipients played a crucial role during nucleation and polymorphic transformation. This alternative, energy-efficient bottom-up method for the production of drug suspensions with a reduced risk of contamination from milling equipment and fewer processing steps may prove to be comparable in terms of stability and particle size distribution to current industrially accepted top-down approaches. |
format | Online Article Text |
id | pubmed-9542716 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-95427162022-10-08 Impact of Excipients and Seeding on the Solid-State Form Transformation of Indomethacin during Liquid Antisolvent Precipitation Hugo Silva, Mariana Kumar, Ajay Hodnett, Benjamin K. Tajber, Lidia Holm, René Hudson, Sarah P. Cryst Growth Des [Image: see text] Long-acting injectables are a unique drug formulation strategy, providing a slow and sustained release of active pharmaceutical ingredients (APIs). In this study, a novel approach that combines liquid antisolvent precipitation with seeding to obtain a stable form of the API indomethacin while achieving the desired particle size distribution is described. It was proven that when a metastable form of indomethacin was initially nucleated, the rate of its transformation to the stable form was influenced by the presence of excipients and seeds (17.10 ± 0.20 μm), decreasing from 48 to 4 h. The final particle size (D50) of the indomethacin suspension produced without seeding was 7.33 ± 0.38 μm, and with seeding, it was 5.61 ± 0.14 μm. Additionally, it was shown that the particle size distribution of the seeds and the time point of seed addition were critical to obtain the desired solid-state form and that excipients played a crucial role during nucleation and polymorphic transformation. This alternative, energy-efficient bottom-up method for the production of drug suspensions with a reduced risk of contamination from milling equipment and fewer processing steps may prove to be comparable in terms of stability and particle size distribution to current industrially accepted top-down approaches. American Chemical Society 2022-09-09 2022-10-05 /pmc/articles/PMC9542716/ /pubmed/36217420 http://dx.doi.org/10.1021/acs.cgd.2c00678 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Hugo Silva, Mariana Kumar, Ajay Hodnett, Benjamin K. Tajber, Lidia Holm, René Hudson, Sarah P. Impact of Excipients and Seeding on the Solid-State Form Transformation of Indomethacin during Liquid Antisolvent Precipitation |
title | Impact of Excipients
and Seeding on the Solid-State
Form Transformation of Indomethacin during Liquid Antisolvent Precipitation |
title_full | Impact of Excipients
and Seeding on the Solid-State
Form Transformation of Indomethacin during Liquid Antisolvent Precipitation |
title_fullStr | Impact of Excipients
and Seeding on the Solid-State
Form Transformation of Indomethacin during Liquid Antisolvent Precipitation |
title_full_unstemmed | Impact of Excipients
and Seeding on the Solid-State
Form Transformation of Indomethacin during Liquid Antisolvent Precipitation |
title_short | Impact of Excipients
and Seeding on the Solid-State
Form Transformation of Indomethacin during Liquid Antisolvent Precipitation |
title_sort | impact of excipients
and seeding on the solid-state
form transformation of indomethacin during liquid antisolvent precipitation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9542716/ https://www.ncbi.nlm.nih.gov/pubmed/36217420 http://dx.doi.org/10.1021/acs.cgd.2c00678 |
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