Extended release pellets prepared by hot melt extrusion technique for abuse deterrent potential: Category-1 in-vitro evaluation
Extended release pellets prepared by hot melt extrusion technique for abuse deterrent potential: Category-1 in-vitro evaluation
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DOI：
10.1016/j.ijpharm.2020.119624
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发表时间：
2020-09-25
影响因子：
5.8
通讯作者：
Repka, Michael A.
中科院分区：
文献类型：
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作者：
Butreddy, Arun;Sarabu, Sandeep;Repka, Michael A.
本研究的目的是利用高相对分子质量的聚环氧乙烷(PEO)和胶凝剂(黄原胶、瓜尔豆胶和结冷胶)研制模型药物对乙酰氨基酚的缓释(ER)热熔挤压(HME)微丸。HME微丸的滥用威慑(AD)潜力通过1类实验室体外评估参数进行评估，包括粒度减小(PSR)、小体积提取、溶出度、粘度、注射性和注射性。此外，还研究了微丸的物理(粉碎)和热(烤箱和微波)操纵性能，以评估AD性能的强度。物理操作研究表明，这些颗粒完好无损，极其坚硬，并能抵抗PSR和绕过ER特性的操作。所有完整和物理操作的微丸在8h内完全释放药物，并观察到在40%乙醇中耐剂量倾倒。在静置、搅拌和热处理条件下，药物浸出量为50%，浸泡时间为30min。与普通PEO微丸相比，PEO/黄原胶微丸在所有操作条件下均表现出更高的粘度、更高的注射器和注射力以及更低的可注射量。这些发现支持PEO和黄原胶颗粒对抗静脉滥用的AD潜力。
The objective of the present study was to develop extended-release (ER) hot-melt extruded (HME) abuse-deterrent pellets of acetaminophen, a model drug, by utilizing high molecular weight polyethylene oxide (PEO) and gelling agents (xanthan gum, guar gum, and gellan gum). The HME pellets were evaluated for their abuse-deterrence (AD) potential by Category-1 laboratory in-vitro evaluation parameters, including particle size reduction (PSR), small volume extraction, dissolution, viscosity, syringeability, and injectability. Further, the pellets were investigated for resistance to physical (crushing) and thermal (oven and microwave) manipulation to evaluate the strength of the AD properties. Physical manipulation studies demonstrated that the pellets were intact, extremely hard, and resistant to PSR and manipulation to bypass ER properties. Dissolution of all intact and physically manipulated pellets led to complete drug release within 8 h, and resistance to dose-dumping in 40% ethanol was observed. The drug extraction was < 50% in 10 mL of ingestible and non-ingestible solvents under static, agitation, and thermal manipulation conditions with an incubation time of 30 min. The PEO/xanthan gum-based formulation showed higher viscosity, syringe and injection forces, and lower syringeable volume in all manipulation conditions compared with plain PEO pellets. These findings supported the AD potential of PEO and xanthan gum pellets against intravenous abuse.