TY  - JOUR
A1  - Spangardt, Christoph
A1  - Keßler, Christoph
A1  - Dobrzewski, Ramona
A1  - Tepler, Antonia
A1  - Hanio, Simon
A1  - Klaubert, Bernd
A1  - Meinel, Lorenz
T1  - Leveraging dissolution by autoinjector designs
JF  - Pharmaceutics
N2  - 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.
KW  - autoinjector
KW  - dissolution
KW  - oxime
KW  - response surface
KW  - nerve agent
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297271
SN  - 1999-4923
VL  - 14
IS  - 11
ER  -