Wang Zijian, Song Sichen, Zhang Hongwei, Liu Xiaohong, A Siegel Ronald, Calvin Sun Changquan, Wang Chenguang
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA; School of Mathematics, University of Minnesota, Minneapolis, MN 55455, USA.
Int J Pharm. 2025 Feb 10;670:125081. doi: 10.1016/j.ijpharm.2024.125081. Epub 2024 Dec 20.
Interest in oral delivery of biological drug products, commonly prepared through lyophilization, is surging. Typically, low solid content solutions are employed for lyophilization to enhance mass transfer and minimize drying time. Yet, this approach often results in lyophilized powders with low bulk density and poor flowability, challenging downstream processing steps that are required for oral product development. Increasing solid content in a starting solution can, in theory, increase the density of lyophilized cakes and powders post-milling. However, the effectiveness of improving powder density and flowability using a higher solid content has not been experimentally verified. In addition, the impact of using a higher solid content on other physicochemical properties of lyophilized materials remains uncertain. To address the knowledge gaps, we lyophilized three common bulk cryoprotectants at two different solid contents (5% and 10%) and systematically evaluated their solid-state properties, bulk density, flowability, compaction characteristics, and physical stability. We found that powders prepared at a higher solid content (10%) exhibited higher bulk density, but they still failed to meet the requirements for easy oral product development. A change in solid content also leads todistinct solid-state properties, compaction behaviors, and stability, highlighting the importance of thorough characterization of lyophilized materials when solid content is changed in the course of oral solid dosage formulation development.
通过冻干法制备的生物药品口服给药方式正受到越来越多的关注。通常，低固含量溶液用于冻干以增强传质并缩短干燥时间。然而，这种方法常常导致冻干粉末的堆积密度低且流动性差，给口服产品开发所需的下游加工步骤带来挑战。理论上，提高起始溶液中的固含量可以增加冻干饼和研磨后粉末的密度。然而，使用更高固含量提高粉末密度和流动性的有效性尚未经过实验验证。此外，使用更高固含量对冻干材料其他物理化学性质的影响仍不确定。为填补这些知识空白，我们以两种不同的固含量（5%和10%）冻干了三种常见的大量冷冻保护剂，并系统地评估了它们的固态性质、堆积密度、流动性、压缩特性和物理稳定性。我们发现，以更高固含量（10%）制备的粉末表现出更高的堆积密度，但它们仍未满足易于口服产品开发的要求。固含量的变化还会导致不同的固态性质、压缩行为和稳定性，这突出了在口服固体剂型开发过程中改变固含量时对冻干材料进行全面表征的重要性。
