Abstract：
Molecular interactions are crucial to stabilize amorphous drugs in amorphous solid dispersions (ASDs). Most polymers, however, have only a limited ability to form strong molecular interactions with drugs. Polymers tailored to fit the physicochemical properties of the drug molecule to be incorporated, for instance by allowing the incorporation of specific functional groups, would be highly sought-for in this regard. For this purpose, the novel allyl-terminated polymer methoxy(polyethylene glycol)-block-poly(jasmine lactone) (mPEG-b-PJL) has been synthesized and functionalized to potentially enhance specific drug-polymer interactions. This study investigated the use of mPEG-b-PJL in ASDs, using carvedilol (CAR), a weakly basic model drug. The findings revealed that the acidic functionalized form of the polymer (mPEG-b-PJL-COOH) indeed established stronger molecular interactions with CAR compared to its non-functionalized counterpart mPEG-b-PJL. Evaluations on polymer effectiveness in forming ASDs demonstrated that mPEG-b-PJL-COOH outperformed its non-functionalized counterpart in miscibility, drug loading ability, and stability, inferred from reduced molecular mobility. However, dissolution tests indicated that ASDs with mPEG-b-PJL-COOH did not significantly improve the dissolution behaviour compared to amorphous CAR alone, despite potential solubility enhancement through micelle formation. Overall, this study confirms the potential of functionalized polymers in ASD formulations, while the challenge of improving dissolution performance in these ASDs remains an area of further development.
摘要：
分子相互作用对于稳定无定形固体分散体（ASD）中的无定形药物至关重要。大多数聚合物，然而,与药物形成强分子相互作用的能力有限。为适应要掺入的药物分子的物理化学性质而定制的聚合物，例如，通过允许结合特定的官能团，在这方面将是非常需要的。为此,新型烯丙基封端的聚合物甲氧基（聚乙二醇）-嵌段-聚（茉莉内酯）（mPEG-b-PJL）已被合成并官能化以潜在地增强特定的药物-聚合物相互作用。本研究调查了mPEG-b-PJL在ASD中的使用，使用卡维地洛（CAR），一种弱基础的模型药物。发现揭示了聚合物的酸性官能化形式(mPEG-b-PJL-COOH)与其非官能化对应物mPEG-b-PJL相比确实建立了与CAR的更强的分子相互作用。对形成ASD的聚合物有效性的评估表明，mPEG-b-PJL-COOH在混溶性方面优于其非官能化对应物，载药能力,和稳定性,从降低的分子迁移率推断。然而,溶出测试表明，与单独使用无定形CAR相比，使用mPEG-b-PJL-COOH的ASD并未显着改善溶出行为。尽管通过胶束形成潜在的溶解度增强。总的来说,这项研究证实了官能化聚合物在ASD配方中的潜力，而改善这些ASD的溶解性能的挑战仍然是进一步发展的领域。
