College of Pharmacy, Health Professions Division, Nova Southeastern University, 3301 College Avenue, Fort Lauderdale, FL 33314-7796, USA.
Int J Pharm. 2019 Oct 5;569:118602. doi: 10.1016/j.ijpharm.2019.118602. Epub 2019 Aug 5.
An innovative abuse-deterrent composition was developed to deter the most dangerous route of drug abuse, the intravenous route. The composition is based on a crosslinked sodium starch glycolate (X-SSG) that can effectively complex with cationic drugs in aqueous solutions and minimize the amount of the free drug available for extraction. Furthermore, the crosslinked polymer swells in and entraps a portion of the drug solution by which it reduces the available volume for syringing and subsequent injection. Two deterrent compositions were prepared, a drug-polymer physical blend and a drug-polymer chemical complex. The composition in its complexed form showed greater deterrence capacity than the physical blend except in solvents with ionic moieties, where the deterrence remained almost the same. The studies revealed that the complexation with the drug played a major role in total drug entrapment. Tablets prepared from the drug-polymer complex showed a complete and immediate drug release in 0.1 N HCl within the first 15 min. Moreover, the dissolution studies in the simulated intestinal media ruled out the re-complexation potential between the drug and the polymer. The proposed X-SSG composition provides a desirable drug release in the gastric and intestinal media under the legitimate use while deterring an intravenous abuse.
一种创新的防滥用组合物被开发出来，以阻止最危险的药物滥用途径，即静脉途径。该组合物基于交联羧甲淀粉钠 (X-SSG)，它可以在水溶液中有效与阳离子药物络合，并将游离药物的含量降到最低，从而减少可供提取的药物量。此外，交联聚合物在其中溶胀并捕获部分药物溶液，从而减少可用于注射器抽吸和随后注射的体积。制备了两种防滥用组合物，一种是药物-聚合物物理混合物，另一种是药物-聚合物化学复合物。除了在含有离子基团的溶剂中外，复合物形式的组合物表现出比物理混合物更大的防滥用能力，而在这些溶剂中，防滥用能力几乎相同。研究表明，与药物的络合在药物的完全包埋中起主要作用。由药物-聚合物复合物制备的片剂在最初的 15 分钟内，在 0.1N HCl 中完全立即释放药物。此外，在模拟肠介质中的溶解研究排除了药物和聚合物之间重新络合的可能性。所提出的 X-SSG 组合物在合法使用时在胃和肠介质中提供了理想的药物释放，同时阻止了静脉滥用。
