TU Dortmund University, Laboratory of Thermodynamics, Department of Biochemical and Chemical Engineering, Emil-Figge-Str. 70, 44227 Dortmund, Germany.
LMU Munich, Chair of Pharmaceutical Technology and Biopharmaceutics, Department of Pharmacy, Butenandtstr. 5, 81377 Munich, Germany.
Int J Pharm. 2023 Apr 5;636:122836. doi: 10.1016/j.ijpharm.2023.122836. Epub 2023 Mar 20.
The glass-transition temperature and the composition of the amorphous phase/maximally concentrated solution (classically referred to as T' and w', respectively) as function of added excipients are crucial for the design of lyophilization processes. Whereas the determination of T' can be accomplished easily using mDSC, the determination of w' poses challenges, since the experimental effort needs to be redone for each new excipient mixture (limited transferability of the results possible). In this work, an approach was developed which allows to predict w' for (1) single excipients, (2) given compositions of a binary excipient mixture, and (3) single excipients in aqueous (model) protein solutions using the thermodynamic model PC-SAFT and one experimental data point of T'. Sucrose, trehalose, fructose, sorbitol, and lactose were considered as single excipients. The binary excipient mixture consisted of sucrose and ectoine. The model protein was bovine serum albumin in combination with sucrose. The results reveal that the new approach can precisely predict w' in the systems considered, including the non-linear course of w' identified for different sucrose/ectoine ratios. The same applies to the course of w' as function of the protein concentration. This newly developed approach allows for the reduction of the experimental effort to a minimum.
玻璃化转变温度和无定形相/最大浓溶液的组成（分别经典地称为 T'和 w'）作为添加赋形剂的函数对于冻干工艺的设计至关重要。虽然使用 mDSC 可以轻松地确定 T'，但 w' 的确定具有挑战性，因为需要为每个新的赋形剂混合物重新进行实验（结果的可转移性有限）。在这项工作中，开发了一种方法，该方法允许使用热力学模型 PC-SAFT 和 T' 的一个实验数据点来预测（1）单一赋形剂、（2）二元赋形剂混合物的给定组成和（3）水（模型）蛋白质溶液中的单一赋形剂中的 w'。蔗糖、海藻糖、果糖、山梨糖醇和乳糖被视为单一赋形剂。二元赋形剂混合物由蔗糖和外消旋肌醇组成。模型蛋白是牛血清白蛋白与蔗糖的组合。结果表明，新方法可以精确预测所考虑的系统中的 w'，包括不同蔗糖/外消旋肌醇比例下确定的 w'的非线性过程。同样适用于 w'作为蛋白质浓度函数的过程。这种新开发的方法可以将实验工作量减少到最低限度。
