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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.

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OBJECTIVE: This study aimed to determine whether selected superabsorbent polymers (SAPs) could be used as a suitable alternative to thwart extraction, filtration, and syringeability attempts for abuse. Many abuse-deterrent formulations (ADFs) rely on high molecular weight polymers such as poly(ethylene oxide) to provide crush and extraction resistance. However, these polymers suffer from slow dissolution kinetics, and are susceptible to a variety of abuse conditions. METHODS: Several commercially available SAPs were evaluated for swelling behavior in extraction solvents, and tableting properties. Post-compaction abuse properties were evaluated by recoverable volume and syringeability after solvent extraction. Drug release and percent drug extraction were conducted using tramadol HCl as a model drug. RESULTS: Certain SAPs had the ability to rapidly imbibe solvent and effectively stop extraction processes in a variety of solvents, including water and water/alcohol mixtures. Tablets containing SAP and drug showed no effect on drug release in vitro. CONCLUSIONS: SAPs possess adequate properties for tableting, and maintain their high and fast swelling properties after compaction. The fast and extensive interactions of SAPs with aqueous medium are a major advantage over non-crosslinked high molecular weight viscosifying agents such as poly(ethylene oxide).

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OBJECTIVES: This study was conducted to evaluate suitable methods of testing crush-resistant tablets composed largely of thermoplastic polymers. The objectives were, i) to evaluate the effect of thermal processes on crush resistance, ii) to develop test method(s) to indicate whether a crush-resistant tablet is susceptible to tampering by insufflation based on generated particle sizes, and iii) to find an appropriate analytical tool for discriminatory studies. METHODS: We investigated the crush-resistance properties of poly(ethylene oxide) (PEO) tablets using three manual and four electrical devices. PEO tablets were directly compressed or further heat-treated to mimic thermal manufacturing processes (i.e. hot-melt extrusion, sintering). Differential scanning calorimetry was also utilized to evaluate effect of thermal processes on polymer properties. RESULTS: Non-heat treated tablets were easily crushed by all methods. Heat-treated tablets were only susceptible to cryogenic grinding and high-powered domestic blender. Our results confirm that manual methods are not suitable for discriminatory study. CONCLUSIONS: Testing methods for crush resistance may not be applicable to all products nor allow control over all process factors. Notwithstanding, the use of high-powered electrical devices may be an effective discriminatory tool for testing heat treated PEO-based ADFs.

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