Abuse of prescription opioids is a global epidemic resulting in an increasing number of deaths. Abuse-deterrent drug products add to the difficulty to improperly use/abuse opioids. Our work is focused on studying the impact of formulation and process variables along with material interactions during the development of polyethylene-oxide-based abuse-deterrent tablets. New in-vitro testing methodologies were also evaluated to improve the formulation screening. These results will help develop high-quality abuse-deterrent opioid drug products.