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Leveraging Dissolution by Autoinjector Designs
Chemical warfare or terrorism attacks with organophosphates may place intoxicated subjects under immediate life-threatening and psychologically demanding conditions. Antidotes, such as the oxime HI-6, which must be formulated as a powder for reconstitution reflecting the molecule’s light sensitivity...
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/PMC9695427/ https://www.ncbi.nlm.nih.gov/pubmed/36432735 http://dx.doi.org/10.3390/pharmaceutics14112544 |
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author | Spangardt, Christoph Keßler, Christoph Dobrzewski, Ramona Tepler, Antonia Hanio, Simon Klaubert, Bernd Meinel, Lorenz |
author_facet | Spangardt, Christoph Keßler, Christoph Dobrzewski, Ramona Tepler, Antonia Hanio, Simon Klaubert, Bernd Meinel, Lorenz |
author_sort | Spangardt, Christoph |
collection | PubMed |
description | Chemical warfare or terrorism attacks with organophosphates may place intoxicated subjects under immediate life-threatening and psychologically demanding conditions. Antidotes, such as the oxime HI-6, which must be formulated as a powder for reconstitution reflecting the molecule’s light sensitivity and instability in aqueous solutions, dramatically improve recovery—but only if used soon after exposure. Muscle tremors, anxiety, and loss of consciousness after exposure jeopardize proper administration, translating into demanding specifications for the dissolution of HI-6. Reflecting the patients’ catastrophic situation and anticipated desire to react immediately to chemical weapon exposure, the dissolution should be completed within ten seconds. We are developing multi-dose and single-dose autoinjectors to reliably meet these dissolution requirements. The temporal and spatial course of dissolution within the various autoinjector designs was profiled colorimetrically. Based on these colorimetric insights with model dyes, we developed experimental setups integrating online conductometry to push experiments toward the relevant molecule, HI-6. The resulting blueprints for autoinjector designs integrated small-scale rotor systems, boosting dissolution across a wide range of viscosities, and meeting the required dissolution specifications driven by the use of these drug products in extreme situations. |
format | Online Article Text |
id | pubmed-9695427 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96954272022-11-26 Leveraging Dissolution by Autoinjector Designs Spangardt, Christoph Keßler, Christoph Dobrzewski, Ramona Tepler, Antonia Hanio, Simon Klaubert, Bernd Meinel, Lorenz Pharmaceutics Article Chemical warfare or terrorism attacks with organophosphates may place intoxicated subjects under immediate life-threatening and psychologically demanding conditions. Antidotes, such as the oxime HI-6, which must be formulated as a powder for reconstitution reflecting the molecule’s light sensitivity and instability in aqueous solutions, dramatically improve recovery—but only if used soon after exposure. Muscle tremors, anxiety, and loss of consciousness after exposure jeopardize proper administration, translating into demanding specifications for the dissolution of HI-6. Reflecting the patients’ catastrophic situation and anticipated desire to react immediately to chemical weapon exposure, the dissolution should be completed within ten seconds. We are developing multi-dose and single-dose autoinjectors to reliably meet these dissolution requirements. The temporal and spatial course of dissolution within the various autoinjector designs was profiled colorimetrically. Based on these colorimetric insights with model dyes, we developed experimental setups integrating online conductometry to push experiments toward the relevant molecule, HI-6. The resulting blueprints for autoinjector designs integrated small-scale rotor systems, boosting dissolution across a wide range of viscosities, and meeting the required dissolution specifications driven by the use of these drug products in extreme situations. MDPI 2022-11-21 /pmc/articles/PMC9695427/ /pubmed/36432735 http://dx.doi.org/10.3390/pharmaceutics14112544 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 | Article Spangardt, Christoph Keßler, Christoph Dobrzewski, Ramona Tepler, Antonia Hanio, Simon Klaubert, Bernd Meinel, Lorenz Leveraging Dissolution by Autoinjector Designs |
title | Leveraging Dissolution by Autoinjector Designs |
title_full | Leveraging Dissolution by Autoinjector Designs |
title_fullStr | Leveraging Dissolution by Autoinjector Designs |
title_full_unstemmed | Leveraging Dissolution by Autoinjector Designs |
title_short | Leveraging Dissolution by Autoinjector Designs |
title_sort | leveraging dissolution by autoinjector designs |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695427/ https://www.ncbi.nlm.nih.gov/pubmed/36432735 http://dx.doi.org/10.3390/pharmaceutics14112544 |
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