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.

Hot-Melt Extrusion of the Thermo-Sensitive Peptidomimetic Drug Enalapril Maleate

“…FT-IR spectrum of SOL showed characteristic bands at 2922 cm −1 (C-H), 2857 cm −1 (C-H), 1740 cm −1 (C=O of the carboxylic group) and 1633 cm −1 (C=O of the amide group) [ 46 , 47 ]. FT-IR spectrum of PEO showed characteristic bands at 2888 cm −1 (C-H), 1240 cm −1 (O-H), 1093 cm −1 (C-O) and 1059 cm −1 (C-O) [ 48 ].…”

Extended release pellets prepared by hot melt extrusion technique for abuse deterrent potential: Category-1 in-vitro evaluation

“…Similarly, the injectability force was observed to be from 2.4 ± 0.4 to 10.8 ± 0.4, 3.5 ± 0.2 to 16.1 ± 0.3 and 2.5 ± 0.4 to 9.1 ± 0.7, respectively for static, agitated, and thermally manipulated pellets. The decrease in resistance to syringe (pulling) and injection (pushing) for the PEO formulation (F1) after thermal manipulation may be due to a reduction in solution viscosity, degradation, and a shortened polymer chain end-to-end distance of PEO after thermal treatment (Joshi et al, 2018). Thus, reduced pulling and pushing forces could be attributed to ease of syringreability and injectability, which led to compromising the IV abuse deterrent potential.…”

“…Thus, the reduction in solution viscosity of the F1 formulation, after thermal manipulation, was due to random chain scission of the PEO structure into smaller fragments at high temperature. Joshi et al, 2018 reported the effect of temperature and concentration of PEO on the solution viscosity. The reduction in solution viscosity was observed as the temperature increased up to 110°C and a further increase in temperature from 110°C to 150°C resulted in a sharp drop in solution viscosity.…”

“…The FDA-approved opioid products with ADF labeling utilize polyethylene oxide (PEO), a commonly used excipient for abuse deterrence. PEO is a nonionic, water-soluble, and thermoplastic homo-polymer with a molecular weight (MW) of 100,000 to 8,000,000 Da and a melting temperature range of 65°C-70°C (Joshi et al, 2018). The PEO-based matrix formulations are prepared using HME technology because of its low melting temperature and thermoplastic nature (Ma et al, 2014;Zhang and McGinity, 1999).…”

Functional properties of thermally tampered poly(ethylene oxide)

“…6 Thermal manipulation is one of the major tools used by abusers to overcome crush resistance and extraction resistance of drug products. 7 Heating high molecular weight PEO close to its degradation temperature may change its chemical structure 8 and diminish crush resistance. Additionally, the high viscosity built up by PEO in water or hydroalcoholic solutions may be significantly lost if the original solid PEO is heated up to its degradation temperature before preparing its aqueous solutions.…”