Institute of Energy and Process Engineering, ETH Zurich, 8092 Zurich, Switzerland.
J Phys Chem Lett. 2023 Jul 6;14(26):5993-6000. doi: 10.1021/acs.jpclett.3c01371. Epub 2023 Jun 22.
The freezing of aqueous solutions is of great relevance to multiple fields, yet the kinetics of ice nucleation, its first step, remains poorly understood. The literature focuses on the freezing of microdroplets, and it is unclear if those findings can be generalized and extended to larger volumes such as those used in the freezing of biopharmaceuticals. To this end, we study ice nucleation from aqueous solutions of ten different compositions in vials at the milliliter scale. The statistical analysis of the approximately 6,000 measured nucleation events reveals that the stochastic ice nucleation kinetics is independent of the nature and concentration of the solute. We demonstrate this by estimating the values of the kinetic parameters in the nucleation rate expression for the selected solution compositions, and we find that a single set of parameters can describe quantitatively the nucleation behavior in all solutions. This holds regardless of whether the nucleation rate is expressed as a function of the chemical potential difference, of the water activity difference, or of the supercooling. While the chemical potential difference is the thermodynamically correct driving force for nucleation and hence is more accurate from a theoretical point of view, the other two expressions allow for an easier implementation in mechanistic freezing models in pharmaceutical manufacturing.
水溶液的冻结与多个领域密切相关，但冰核形成的动力学，即其第一步，仍未被充分理解。文献主要集中在微液滴的冻结上，尚不清楚这些发现是否可以推广和扩展到更大的体积，如生物制药冻结中使用的体积。为此，我们在毫升规模的小瓶中研究了十种不同组成的水溶液中的成核过程。对大约 6000 次测量成核事件的统计分析表明，随机成核动力学与溶质的性质和浓度无关。我们通过估计所选溶液组成的成核率表达式中的动力学参数值来证明这一点，我们发现一组参数可以定量描述所有溶液中的成核行为。无论成核率是表示为化学势差、水活度差还是过冷度的函数，都是如此。虽然化学势差是成核的热力学正确驱动力，因此从理论角度来看更准确，但其他两种表达式在制药生产中的机械冻结模型中更容易实现。
