Misuse of prescription opioid drugs is the leading cause of the opioid crisis and overdose-related death. Abuse deterrent formulations (ADFs) have been developed to discourage attempts to tamper with the formulation and alter the ingestion methods. However, abusers develop complex extraction strategies to circumvent the ADF technologies. For comprehensive deterrence of drug abuse, we develop tannic acid nanoparticles (NPs) that protect encapsulated opioids from solvent extraction and thermal challenge (crisping), complementing the existing formulation strategy to deter injection abuse. Here, we develop a hybrid ADF tablet (NP-Tab), consisting of iron-crosslinked tannic acid NPs encapsulating thebaine (model opioid compound), xanthan gum, and chitosan (gel-forming polymers), and evaluate its performance in common abuse conditions. NP-Tab tampered by crushing and suspended in aqueous solvents forms an instantaneous gel, which is difficult to pull or push through a 21-gauge needle. NPs insulate the drug from organic solvents, deterring solvent extraction. NPs also promote thermal destruction of the drug to make crisping less rewarding. However, NP-Tab releases thebaine in the simulated gastric fluid without delay, suggesting that its analgesic effect may be unaffected if consumed orally as prescribed. These results demonstrate that NP-Tab can provide comprehensive drug abuse deterrence, resisting aqueous/organic solvent extraction, injection, and crisping, while retaining its therapeutic effect upon regular usage.

中文翻译：

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使用纳米颗粒-聚合物混合制剂进行多维阿片类药物滥用威慑

滥用处方阿片类药物是阿片类药物危机和过量相关死亡的主要原因。滥用威慑制剂（ADF）的开发是为了阻止篡改制剂和改变摄入方法的企图。然而，滥用者制定了复杂的提取策略来规避 ADF 技术。为了全面遏制药物滥用，我们开发了单宁酸纳米颗粒 (NP)，可保护封装的阿片类药物免受溶剂萃取和热挑战（脆化），补充了现有的防止注射滥用的配方策略。在这里，我们开发了一种混合 ADF 片剂 (NP-Tab)，由封装蒂巴因（模型阿片化合物）、黄原胶和壳聚糖（凝胶形成聚合物）的铁交联单宁酸 NP 组成，并评估其在常见滥用条件下的性能。 NP-Tab 通过压碎和悬浮在水性溶剂中而形成瞬时凝胶，很难通过 21 号针头拉动或推动。纳米颗粒将药物与有机溶剂隔离，阻止溶剂萃取。纳米颗粒还会促进药物的热破坏，从而降低脆化效果。然而，NP-Tab 在模拟胃液中立即释放蒂巴因，这表明如果按处方口服，其镇痛效果可能不受影响。这些结果表明，NP-Tab 可以提供全面的药物滥用威慑，抵抗水/有机溶剂提取、注射和脆化，同时在经常使用时保留其治疗效果。