Li David, Chow Poh Yee, Lin Tzu Ping, Cheow Celine, Li Zhuoxuan, Wacker Matthias G
National University of Singapore, Faculty of Science, 4 Science Drive 2, 117544 Singapore.
National University of Singapore, Faculty of Science, 4 Science Drive 2, 117544 Singapore.
J Pharm Sci. 2023 Jun;112(6):1492-1508. doi: 10.1016/j.xphs.2021.10.031. Epub 2021 Oct 30.
For decades, there has been a growing interest in injectable subcutaneous formulations to improve the absorption of drugs into the systemic circulation and to prolong their release over a longer period. However, fluctuations in the blood plasma levels together with bioavailability issues often limit their clinical success. This warrants a closer look at the performance of long-acting depots, for example, and their dependence on the complex interplay between the dosage form and the physiological microenvironment. For this, biopredictive performance testing is used for a thorough understanding of the biophysical processes affecting the absorption of compounds from the injection site in vivo and their simulation in vitro. In the present work, we discuss in vitro methodologies including methods and media developed for the subcutaneous route of administration on the background of the most relevant absorption mechanisms. Also, we highlight some important knowledge gaps and shortcomings of the existing methodologies to provide the reader with a better understanding of the scientific evidence underlying these models.
几十年来，人们对可注射皮下制剂的兴趣与日俱增，希望借此提高药物进入体循环的吸收效率，并延长其释放时间。然而，血浆水平的波动以及生物利用度问题常常限制了它们在临床上的成功应用。这就需要更深入地研究长效贮库的性能，例如，以及它们对剂型与生理微环境之间复杂相互作用的依赖性。为此，生物预测性能测试被用于全面了解影响体内化合物从注射部位吸收的生物物理过程以及它们在体外的模拟情况。在本研究中，我们将在最相关吸收机制的背景下讨论体外方法，包括为皮下给药途径开发的方法和介质。此外，我们还强调了现有方法存在的一些重要知识空白和不足之处，以便让读者更好地理解这些模型背后的科学依据。
