Determining Abuse Deterrence Performance of Poly (ethylene oxide) Using a Factorial Design

Abstract

Purpose: The purpose of this study was to determine the effects of thermal processing and antioxidant formulation variables on the abuse deterrence performance of a high molecular weight poly(ethylene oxide) (PEO) polymer. Methods: A 24 factorial design with one categorical factor (antioxidant type) and three continuous factors (curing time, curing temperature, % antioxidant) was used. Abuse deterrence performance was evaluated using solution viscosity, surface melting temperature, and mechanical strength. Thermal degradation of PEO powders before compaction was also studied using DSC, FTIR spectroscopy, and viscosity analysis. Results: Our results showed that curing temperature and type of antioxidant can significantly affect the deterrence performance of PEO. The main effect plot for viscosity shows the most prominent factors affecting viscosity are curing temperature and type of antioxidant. However, curvature in the linear model obtained was not sufficient to completely describe the behavior. For surface melting temperature, butylated hydroxytoluene was associated with higher surface melting temperatures compared to ascorbic acid. Additionally, higher percent of antioxidant resulted in higher melting temperature. Particle size distribution to indicate mechanical strength showed no significant effects of tested factors. This suggests that comminution method has more prominent effect on tablet fragment size than the formulation and processing factors studied. Conclusion: While heat confers the mechanical strength to the polymer, it can diminish its physical stability and solution state viscosity. The experimental studies showed that prolonged exposure to high temperatures, even in the presence of antioxidants, can severely hamper polymer deterrence performance in both solid and solution states.

Keywords: Abuse deterrent formulation, Injecting drug use, Crush resistance, Opioid abuse, Poly(ethylene oxide)