Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Spangardt, Christoph, Keßler, Christoph, Dobrzewski, Ramona, Tepler, Antonia, Hanio, Simon, Klaubert, Bernd, Meinel, Lorenz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784838057349873664
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
work_keys_str_mv AT spangardtchristoph leveragingdissolutionbyautoinjectordesigns
AT keßlerchristoph leveragingdissolutionbyautoinjectordesigns
AT dobrzewskiramona leveragingdissolutionbyautoinjectordesigns
AT teplerantonia leveragingdissolutionbyautoinjectordesigns
AT haniosimon leveragingdissolutionbyautoinjectordesigns
AT klaubertbernd leveragingdissolutionbyautoinjectordesigns
AT meinellorenz leveragingdissolutionbyautoinjectordesigns