College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, USA.
College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA.
Int J Pharm. 2021 May 1;600:120481. doi: 10.1016/j.ijpharm.2021.120481. Epub 2021 Mar 22.
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.
聚环氧乙烷（PEO）是在滥用防御配方（ADFs）中最常用的阻止剂。在这项研究中，我们研究了 PEO 在高温（80°C 和 180°C）下加热后的滥用防御特性及其潜在的细胞毒性。结果表明，聚合物的粉碎和提取阻力特性显著丧失，这主要与聚合物在较高温度下的降解有关。还发现，在高温下处理的 PEO 失去了其控制释放特性，在模拟胃液中一个小时后，超过 80%的药物被释放。进一步评估了 PEO 的细胞毒性，以评估聚合物在热处理后的安全性。我们的研究结果表明，暴露于高温处理的 PEO 的细胞活力显著丧失。总的来说，将 PEO 加热到高温会导致粉碎/提取阻力特性和聚合物安全性的显著丧失。这些发现再次强调，需要更合适和更严格的测试和法规来确保滥用防御配方在滥用的恶劣条件下是安全有效的。
