Biomedical Science, Malmö University, Malmö, Sweden; Biofilms research center for Biointerfaces, Malmö, Sweden; NextBioForm Competence Centre, Stockholm, Sweden.
RISE Research Institutes of Sweden, Stockholm, Sweden; NextBioForm Competence Centre, Stockholm, Sweden.
J Pharm Sci. 2022 Jul;111(7):2030-2037. doi: 10.1016/j.xphs.2022.01.027. Epub 2022 Feb 1.
The ice crystallization and melting in systems where the equilibrium state is difficult to reach is one of the growing areas in pharmaceutical freeze-drying research. The quality of the final freeze-dried product depends on the parameters of the cooling step, which affect the ice nucleation and growth. In this paper, we present a DSC study of ice crystallization and melting in a sucrose-water system. Using two different types of thermal cycles, we examine the influence of cooling and heating rates on the thermal behavior of sucrose-water solutions with water contents between 50 and 100 wt%. The DSC results show that low cooling rates provide crystallization at higher temperatures and lead to lower amount of non-freezing water. Consequently, the glass transition and ice melting properties observed upon heating depend on the cooling conditions in the preceding step. Based on the experimental results, we investigate the reasons for the existence of the two steps on DSC heating curves in sucrose-water systems: the glass transition step and the onset of ice melting. We show that diffusion of water can be the limiting factor for ice growth and melting in the sucrose-water system when the amorphous phase is in a liquid state. In particular, when the diffusion coefficient drops below 10 m/sec, the ice crystals growth or melting becomes strongly suppressed even above the glass transition temperature. Understanding the diffusion limitations in the sucrose-water system can be used for the optimization of the freeze-drying protocols for proteins and probiotics.
在平衡状态难以达到的体系中，冰的结晶和融化是药物冷冻干燥研究中日益增长的领域之一。最终冷冻干燥产品的质量取决于冷却步骤的参数，这些参数会影响冰的成核和生长。在本文中，我们进行了 DSC 研究，以了解蔗糖-水体系中的冰结晶和融化。我们使用两种不同类型的热循环，研究了冷却和加热速率对水含量在 50 至 100wt%之间的蔗糖-水溶液热行为的影响。DSC 结果表明，较低的冷却速率在较高温度下提供结晶，并导致非冻结水的量减少。因此，在加热过程中观察到的玻璃化转变和冰熔化特性取决于前一步骤中的冷却条件。基于实验结果，我们研究了蔗糖-水体系 DSC 加热曲线上存在两个步骤（玻璃化转变步骤和冰熔化起始步骤）的原因。我们表明，当非晶相处于液态时，水的扩散可能是蔗糖-水体系中冰生长和熔化的限制因素。特别是当扩散系数降至 10m/sec 以下时，即使在玻璃化转变温度以上，冰晶的生长或熔化也会受到强烈抑制。了解蔗糖-水体系中的扩散限制可以用于优化蛋白质和益生菌的冷冻干燥方案。
