Biphase Extended Release Tablet Formulation for Nerve Agent Pretreatment

Nerve agents exert their toxic effect by binding to and inactivating enzyme acetylcholinesterase, a key enzymatic regulator of cholinergic neurotransmission. The binding becomes irreversible after a varying amount of time with nerve agents and this aging process limits the treatment window of oxime reactivators. To enhance the current antidote treatment of nerve agent autoinjectors, a pyridostigmine pretreatment with 30-mg tablets of pyridostigmine bromide is authorized to use in a potential nerve agent exposure to soldiers. Pyridostigmine reversibly bind and inhibit a critical number of acetylcholinesterase, protecting them from the irreversible inhibition by Soman. However the approved 30-mg PB tablet is only effective for less than 8 hours and soldiers are required to take the medicine three times a day. In an effort to reduce logistic burdens and improve medication compliance, Zymeron proposes to develop an extended release tablet that can sustain the drug levels in the blood for 24 hours allowing once daily administration. The novel formulation is also thermally stable and resistant to moisture so that it has prolonged shelf-life when stored under ambient conditions.