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Assessment of Diverse Solid−State Accelerated Autoxidation Methods for Droperidol
The present study aimed to investigate methods for accelerating autoxidation of crystalline drugs in the solid-state that can potentially predict real−time stability. Solid droperidol (DPD) was selected as the model drug. A common free−radical initiator, 2,2′−azobisisobutyronitrile (AIBN), was used...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227907/ https://www.ncbi.nlm.nih.gov/pubmed/35745687 http://dx.doi.org/10.3390/pharmaceutics14061114 |
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author | Iyer, Jayant Saraf, Isha Ray, Andrew Brunsteiner, Michael Paudel, Amrit |
author_facet | Iyer, Jayant Saraf, Isha Ray, Andrew Brunsteiner, Michael Paudel, Amrit |
author_sort | Iyer, Jayant |
collection | PubMed |
description | The present study aimed to investigate methods for accelerating autoxidation of crystalline drugs in the solid-state that can potentially predict real−time stability. Solid droperidol (DPD) was selected as the model drug. A common free−radical initiator, 2,2′−azobisisobutyronitrile (AIBN), was used to induce autoxidation in solutions. AIBN decomposes at elevated temperatures to yield carbon−centred cyano−isopropyl free radicals that can auto−oxidize neighboring drug molecules. Although the reaction of AIBN is relatively straightforward in solution, it is less so in solids. In this study, we used solid AIBN mixed with DPD powder in the presence and absence of pressurized oxygen headspace. Samples were prepared directly in the form of binary mixtures with DPD and additionally in the form of powder compact/pellet with DPD. The main challenge in carrying out the reaction was related to the preservation of AIBN at elevated temperatures due to the disintegration of the pellet containing the latter. A commercially available free−radical coated silica particle (i.e., 2,2,6,6−tetramethyl−1−piperinyloxy (TEMPO) or (SiliaCAT(TM) TEMPO)) was tested as a potential stressor, but with limited success to induce autoxidation. The most valuable results were obtained when a physical mixture of pre−milled PVP K−60 containing free radicals and DPD was exposed to elevated oxygen−temperature conditions, which yielded significant degradation of DPD. The study highlights the practical challenges for conducting accelerated solid−state stress studies to assess the autoxidation susceptibility of drugs using traditional free−radical initiators and presents a proof of application of milled PVP with free−radical as a potential alternative. |
format | Online Article Text |
id | pubmed-9227907 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92279072022-06-25 Assessment of Diverse Solid−State Accelerated Autoxidation Methods for Droperidol Iyer, Jayant Saraf, Isha Ray, Andrew Brunsteiner, Michael Paudel, Amrit Pharmaceutics Communication The present study aimed to investigate methods for accelerating autoxidation of crystalline drugs in the solid-state that can potentially predict real−time stability. Solid droperidol (DPD) was selected as the model drug. A common free−radical initiator, 2,2′−azobisisobutyronitrile (AIBN), was used to induce autoxidation in solutions. AIBN decomposes at elevated temperatures to yield carbon−centred cyano−isopropyl free radicals that can auto−oxidize neighboring drug molecules. Although the reaction of AIBN is relatively straightforward in solution, it is less so in solids. In this study, we used solid AIBN mixed with DPD powder in the presence and absence of pressurized oxygen headspace. Samples were prepared directly in the form of binary mixtures with DPD and additionally in the form of powder compact/pellet with DPD. The main challenge in carrying out the reaction was related to the preservation of AIBN at elevated temperatures due to the disintegration of the pellet containing the latter. A commercially available free−radical coated silica particle (i.e., 2,2,6,6−tetramethyl−1−piperinyloxy (TEMPO) or (SiliaCAT(TM) TEMPO)) was tested as a potential stressor, but with limited success to induce autoxidation. The most valuable results were obtained when a physical mixture of pre−milled PVP K−60 containing free radicals and DPD was exposed to elevated oxygen−temperature conditions, which yielded significant degradation of DPD. The study highlights the practical challenges for conducting accelerated solid−state stress studies to assess the autoxidation susceptibility of drugs using traditional free−radical initiators and presents a proof of application of milled PVP with free−radical as a potential alternative. MDPI 2022-05-24 /pmc/articles/PMC9227907/ /pubmed/35745687 http://dx.doi.org/10.3390/pharmaceutics14061114 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Iyer, Jayant Saraf, Isha Ray, Andrew Brunsteiner, Michael Paudel, Amrit Assessment of Diverse Solid−State Accelerated Autoxidation Methods for Droperidol |
title | Assessment of Diverse Solid−State Accelerated Autoxidation Methods for Droperidol |
title_full | Assessment of Diverse Solid−State Accelerated Autoxidation Methods for Droperidol |
title_fullStr | Assessment of Diverse Solid−State Accelerated Autoxidation Methods for Droperidol |
title_full_unstemmed | Assessment of Diverse Solid−State Accelerated Autoxidation Methods for Droperidol |
title_short | Assessment of Diverse Solid−State Accelerated Autoxidation Methods for Droperidol |
title_sort | assessment of diverse solid−state accelerated autoxidation methods for droperidol |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227907/ https://www.ncbi.nlm.nih.gov/pubmed/35745687 http://dx.doi.org/10.3390/pharmaceutics14061114 |
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