Purcell Mona, Babaee Sahab, Galluppi Michael, Cline John, Hu Guangli, Petrescu Ioan, Hughes Jennifer, Allen Meredith, Messina Eric, Persak Steven, Krishnamachari Yogita, Lay-Fortenbery Ashley, Miller Corin O
Translational Imaging, Merck Research Laboratories, Merck and Co., Inc., Rahway, NJ, United States.
Device Development, Merck Research Laboratories, Merck and Co., Inc., Rahway, NJ, United States.
Front Drug Deliv. 2023 Jul 13;3:1223177. doi: 10.3389/fddev.2023.1223177. eCollection 2023.
Many commercially available biologics, previously delivered only intravenously, are being re-formulated for subcutaneous delivery to improve patient access and compliance. However, due to inherent solubility limitations, large volume injections (more than 2 mL) are typically required. Different strategies are being explored to improve the tolerability of such injections, including the co-formulation with hyaluronidase and/or implementing different needle designs. While there have been separate reports of measuring injection forces and using imaging to track injection delivery and tissue response, there is no current set of methods to simultaneously characterize the injection delivery (bleb) and measure injection pressures. In this study we describe the development of Computed Tomography imaging methods in minipigs to characterize the morphology of the bleb following injection, along with inline pressure measurements to assess subcutaneous pressure during injection using two different injection volumes, 4.5 mL and 9 mL. We show that these parameters change with injection volume, and that inclusion of hyaluronidase in the injection increases bleb dispersion and reduces skin distention while also lowering the injection pressure. This method will likely be a valuable tool for assessing and comparing different injection delivery methods and formulations.
许多市售生物制剂以前仅通过静脉注射给药，现在正重新配制为皮下给药，以提高患者的接受度和依从性。然而，由于固有的溶解度限制，通常需要大容量注射（超过2毫升）。目前正在探索不同的策略来提高此类注射的耐受性，包括与透明质酸酶共同配制和/或采用不同的针头设计。虽然已有关于测量注射力以及使用成像技术跟踪注射给药和组织反应的单独报道，但目前尚无一套方法能够同时表征注射给药（水疱）并测量注射压力。在本研究中，我们描述了在小型猪中开发计算机断层扫描成像方法，以表征注射后水疱的形态，同时进行在线压力测量，以评估使用4.5毫升和9毫升两种不同注射体积进行注射时的皮下压力。我们表明，这些参数会随注射体积而变化，并且在注射中加入透明质酸酶会增加水疱扩散、减少皮肤扩张，同时还会降低注射压力。该方法可能是评估和比较不同注射给药方法和制剂的宝贵工具。
