Zymeron Corporation, United States
Keywords: Chemoprophylaxis, Nerve Agents, Pyridostigmine Bromide, Extended ReleasePyridostigmine bromide (PB) 30-mg tablets is the currently FDA-approved pretreatment medication (e.g. SNAPP) for use against the lethal effects of nerve agent (e.g., soman) poisoning. The dose of PB pretreatment is one 30 mg SNAPP tablet every 8 hours. It would be beneficial to soldiers with less dosing frequency such as once daily to reduce the drug regimen complexity and improve medication adherence. Additionally, the 30 mg PB immediate release tablets are hygroscopic and must be stored in refrigeration and protected from light. The shelf-life at ambient temperature and humidity is three months, after which the blister pack must be discarded. Therefore, to develop a PB formulation with improved stability would significantly reduce costs and lower logistic burden. Here we developed a series of extended release PB formulations. Sustained release for 24 hours were demonstrated in vitro. Improved bioavailability, sufficiently long duration of effective concentration and rapid onset of action were demonstrated in the rat PK study. Simulated PK curves for humans provided additional evidence for Zymeron’s extended release technology to enable daily oral dosing regimen. In addition, we have demonstrated that the moisture uptake of the SNAPP tablets were significantly reduced by applying moisture protection polymer film coating.