Abuse-deterrent properties and cytotoxicity of poly(ethylene oxide) after thermal tampering

• Published in: International journal of pharmaceutics 2021-05, Vol.600, p.120481-120481, Article 120481
• Main Authors: Babanejad, Niloofar, Kandalam, Umadevi, Ahmad, Rand, Omidi, Yadollah, Omidian, Hamid
• Format: Article
• Language: English
• Subjects: Abuse-deterrent; Crush resistance; Cytotoxicity; Heat treatment; Poly(ethylene oxide)
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2021.120481

[Display omitted] Poly(ethylene oxide) (PEO) is the most common deterring agent used in the abuse-deterrent formulations (ADFs). In this study, we investigated the PEO's abuse-deterrent properties and its potential cytotoxicity after being heated at high temperatures (80 °C and 180 °C). The results indicated a significant loss in both crush and extraction resistance features of the polymer, which is primarily associated with the polymer degradation at the higher temperatures. The heat-treated PEO at the high temperature was also found to lose its controlled-release feature, upon which over 80% of the drug was released after one hour in the simulated gastric fluid. The cytotoxicity of the PEO was further assessed to evaluate the safety of the polymer following the thermal treatment. Our findings revealed a substantial loss in the viability of the cells exposed to the PEO treated at higher temperatures. Taken all, heating PEO at high temperatures can lead to a significant loss in both the crush/extraction resistance characteristics and the safety of the polymer. These findings reemphasize the fact that more appropriate and stricter test and regulations will be needed to assure that the abuse deterrent formulations are safe and effective under severe conditions of abuse.