Dual Formulation of Atropine/Scopolamine with Enhanced Stability

The current US military standard-of-care for organophosphorus nerve agent poisoning is the application of atropine sulfate and 2-pralidoxime autoinjectors, targeting the reversal of acetylcholinesterase enzyme inhibition (via 2-PAM) and the management of OPNA symptoms (via atropine). However, atropine efficacy is largely limited to the periphery and its inability to pass the blood brain barrier and affect the central nervous system. Scopolamine hydrobromide has been demonstrated to effectively cross the blood brain barrier for management of nerve agent poisoning symptoms, and may additionally reduce OPNA-induced seizures. A dual formulation of both atropine and scopolamine as an injectable would therefore be extremely beneficial to the warfighter for treating acute OPNA poisoning and improving patient outcomes. However, a stable co-formulation of these therapeutics has not been previously demonstrated. We propose to develop a stable, efficacious dual formulation of atropine and scopolamine for intramuscular injection to treat OPNA poisoning, with a stable shelf life of at least two years and a volume of 2 mL or less.