Butreddy Arun, Sarabu Sandeep, Dumpa Nagireddy, Bandari Suresh, Repka Michael A
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA; Pii Center for Pharmaceutical Technology, The University of Mississippi, University, MS 38677, USA.
Int J Pharm. 2020 Sep 25;587:119624. doi: 10.1016/j.ijpharm.2020.119624. Epub 2020 Jul 10.
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.
本研究的目的是通过使用高分子量聚环氧乙烷（PEO）和胶凝剂（黄原胶、瓜尔胶和结冷胶）来开发对乙酰氨基酚（一种模型药物）的缓释（ER）热熔挤出（HME）抗滥用微丸。通过1类实验室体外评估参数对HME微丸的抗滥用（AD）潜力进行评估，这些参数包括粒径减小（PSR）、小体积萃取、溶出度、粘度、可注射性和注射性。此外，研究了微丸对物理（压碎）和热（烘箱和微波）处理的抗性，以评估AD特性的强度。物理处理研究表明，微丸完整、极其坚硬，并且对PSR和绕过ER特性的处理具有抗性。所有完整和经过物理处理的微丸的溶出均导致药物在8小时内完全释放，并且观察到在40%乙醇中具有抗剂量倾泻作用。在静态、搅拌和热处理条件下，孵育时间为30分钟时，在10 mL可食用和不可食用溶剂中药物萃取率<50%。与普通PEO微丸相比，基于PEO/黄原胶的制剂在所有处理条件下均表现出更高的粘度、注射器和注射力以及更低的可注射体积。这些发现支持了PEO和黄原胶微丸对静脉内滥用的AD潜力。
