# Stability of Multicomponent Antidote Parenteral Formulations for Autoinjectors against Chemical War Agents (Neurotoxics)

## TL;DR

This study evaluates the stability of antidote formulations in autoinjectors under various conditions to find the most effective combination for treating neurotoxic war agents.

## Contribution

The study identifies the most stable drug combination and sealing material for antidote autoinjectors under different storage conditions.

## Key findings

- Midazolam was found to be unstable under all tested conditions.
- Drug adsorption was significantly influenced by the lipophilicity of the drug.
- The most stable formulation was pralidoxime and atropine at pH 4 with the 4023/50 GRAY sealing material.

## Abstract

Combinations of different drugs are formulated in autoinjectors for parenteral administration against neurotoxic war agents. In this work, the effects on the chemical stability of the following three variables were studied: (i) type of drug combination (pralidoxime, atropine, and midazolam versus obidoxime, atropine, and midazolam); (ii) pH (3 versus 4); and (iii) type of elastomeric sealing material (PH 701/50 C BLACK versus 4023/50 GRAY). Syringes were stored at three different temperatures: 4, 25, and 40 °C. Samples were assayed at different time points to study the physical appearance, drug sorption on the sealing elastomeric materials, and drug content in solution. Midazolam was unstable in all tested experimental conditions. Drug adsorption was observed in both types of sealing elastomeric materials and was significantly (p < 0.01) dependent on the lipophilicity of the drug. The most stable formulation was the combination of pralidoxime and atropine at pH 4 with the elastomeric sealing material 4023/50 GRAY.