DEVELOPING IN-VITRO TESTS FOR SOLID-STATE ABUSE DETERRENCE CAPACITY

Objective. The main objective of this study was 1) to develop standard testing practices to be used when evaluating crush resistance properties of abuse deterrent formulations, and 2) to determine which methods of particle size reduction (manual or electrical) are the most discriminatory for measuring crush resistance of tablet dosage forms. Background. Crushing, or particle size reduction, is often the first step to make a medication easier to snort, to dissolve for injection, or to destroy slowrelease mechanisms in order to achieve greater euphoric effects. However, no standard methods exist on testing crush resistant properties of prescription medications susceptible to abuse. Such testing is crucial for comparative purposes and to obtain abuse-deterrent labelling for the newly-marketed abuse-deterrent products. Methods. Tablets containing poly(ethylene oxide) as a deterrent agent and acetaminophen as model drug were formulated on tablet press (2000 pounds) before undergoing a post compaction thermal process reported for a crush-resistant marketed formulation. Crush resistance was then assessed using manual (i.e., pill crusher, pestle-mortar) and mechanical (i.e., hardness tester, ball mill, high shear grinder, domestic blender) methods at different time durations and sample mass. The resultant product was then analyzed by sieve analysis. Results. Significant differences were observed between the particle size distributions using different methods. The domestic blender and high shear grinder had better ability to differentiate products compared to other tooling. Conclusion. There is no universal method to measure crush resistance, and methods used to perform particle size reduction can display different level of resistance to manipulation Grants. NSU grants # 335357 and 33582