Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
J Pharm Sci. 2020 Mar;109(3):1356-1364. doi: 10.1016/j.xphs.2019.12.005. Epub 2019 Dec 7.
High drug cargo loading in polymer and physical stability was essential for the development of orodispersible films (ODFs) because of the small amount of excipients used in a thin film. The present study aimed to investigate the mechanism of ion-pair strategy in improving drug cargo loading and physical stability of drug in ODFs. The results showed that the ion pair, especially ibuprofen-ethanolamine, improved the drug solubility in polymer up to 60% (w/w) and physical stability by 30% than the pure ibuprofen film. In addition, drug dissolution rate was increased over 2 times. The high drug cargo loading, physical stability and drug dissolution rate was derived from the improved the drug-polymer miscibility introduced by the formation of ion-pair complex. Investigations from the standpoint of physicochemical properties, intermolecular interaction, and polymer mobility indicated the modulation mechanism of ion-pair complexes in the ODFs at molecular level. The amino group and -OH of counter ion exhibited strong hydrogen bond forming ability, which increased the bilateral interaction with both drug and polymer, delayed the onset temperature of sublimation and decreased the polymer mobility. Therefore, ion-pair technology is a promising strategy for high drug loading ODFs in improving the drug-excipient miscibility and stability.
高载药量和聚合物的物理稳定性对于口崩膜（ODF）的开发至关重要，因为在薄膜中使用的辅料量很少。本研究旨在探讨离子对策略提高ODF 中药物载药量和药物物理稳定性的机制。结果表明，与纯布洛芬薄膜相比，离子对（特别是布洛芬-乙醇胺）将药物在聚合物中的溶解度提高了 60%（w/w），并将物理稳定性提高了 30%。此外，药物溶出率提高了 2 倍以上。高载药量、物理稳定性和药物溶出率源于形成离子对复合物所带来的改善药物-聚合物混溶性。从物理化学性质、分子间相互作用和聚合物迁移率的角度对离子对复合物在 ODF 中的分子水平调制机制进行了研究。抗衡离子的氨基和-OH 表现出很强的氢键形成能力，这增加了与药物和聚合物的双边相互作用，延迟了升华的起始温度并降低了聚合物的迁移率。因此，离子对技术是提高载药量高的 ODF 中药物-赋形剂混溶性和稳定性的一种很有前途的策略。
