Patil Chanakya D, Tejasvi Mutukuri Tarun, Santosh Arte Kinnari, Huang Yijing, Radhakrishnan Vinay, Tony Zhou Qi
Department of Industrial and Molecular Pharmaceutics, College of Pharmacy, Purdue University, West Lafayette, IN 47907, USA.
Injectable Drug Product Development, Alexion Pharmaceuticals, Inc. (AstraZeneca Rare Disease Unit), New Haven, CT 06510, USA.
Int J Pharm. 2025 Jan 5;668:124974. doi: 10.1016/j.ijpharm.2024.124974. Epub 2024 Nov 19.
Solid-state protein formulations are known to exhibit enhanced storage stability compared to their liquid dosage form counterparts. pH is one of the factors affecting the stability of protein formulations. The pH of protein formulations in the solution could be influenced by the buffer used, directly impacting their solid-state stability. During lyophilization, buffer components may interact with other formulation components present in the protein formulations, causing a pH shift. This study aimed to investigate the effects of phosphate buffer and amino acid buffers (such as histidine and/or arginine) on the physical properties and accelerated storage stability of spray freeze-dried or lyophilized protein formulations. A model protein, bovine serum albumin (BSA), was used to prepare high-concentration protein formulations. The formulations consisted of BSA, trehalose, and mannitol in an 80:15:5 ratio (w/w), respectively. Various buffers were utilized in the preparation of protein formulations, and the resultant solid formulations underwent screening via accelerated stability study using size exclusion chromatography (SEC). The combination of phosphate and arginine buffers resulted in increased monomer loss in the accelerated storage stability study. Additional characterizations, including solid-state Fourier transform infrared spectroscopy (ssFTIR) and powder X-ray diffraction (PXRD), were conducted. While these analyses did not definitively elucidate the mechanism behind the observed instability, their outcomes provide valuable insights for further investigation, highlighting the need for future research in this area.
与液体剂型的蛋白质制剂相比，固态蛋白质制剂具有更高的储存稳定性。pH值是影响蛋白质制剂稳定性的因素之一。溶液中蛋白质制剂的pH值可能会受到所用缓冲液的影响，直接影响其固态稳定性。在冻干过程中，缓冲液成分可能会与蛋白质制剂中存在的其他制剂成分相互作用，导致pH值发生变化。本研究旨在探讨磷酸盐缓冲液和氨基酸缓冲液（如组氨酸和/或精氨酸）对喷雾冷冻干燥或冻干蛋白质制剂的物理性质和加速储存稳定性的影响。使用模型蛋白牛血清白蛋白（BSA）制备高浓度蛋白质制剂。这些制剂分别由BSA、海藻糖和甘露醇按80:15:5的比例（w/w）组成。在蛋白质制剂的制备过程中使用了各种缓冲液，所得的固体制剂通过尺寸排阻色谱（SEC）进行加速稳定性研究筛选。在加速储存稳定性研究中，磷酸盐和精氨酸缓冲液的组合导致单体损失增加。还进行了其他表征，包括固态傅里叶变换红外光谱（ssFTIR）和粉末X射线衍射（PXRD）。虽然这些分析没有明确阐明观察到的不稳定性背后的机制，但其结果为进一步研究提供了有价值的见解，突出了该领域未来研究的必要性。
