Observations on the Changing Shape of the Ice Mass and the Determination of the Sublimation End Point in Freeze-Drying: An Application for Through-Vial Impedance Spectroscopy (TVIS)

This entry contains the figures and original data for our publication in the journal "Pharmaceutics"<br>Abstract : Models for ice sublimation from a freeze-drying vial rely on the assumption of a planar ice interface up to ~25% loss of ice mass (which is difficult to qualify) whereas single-vial determinations of the sublimation endpoint (by temperature sensors) are based on the point when the observed temperature reaches a plateau, which cannot differentiate between sublimation and desorption-drying. In this work, the real part capacitance of TVIS vial(s) containing frozen water (during sublimation drying) was measured at 100 kHz. This parameter was shown to be highly sensitive to the shape and volume of the ice mass and is therefore a useful parameter for monitoring ice sublimation. By placing a digital camera in front of an isolated TVIS vial containing ice, it was possible to relate the changes in the shape of the ice mass with the changes in the trajectory of the time profile of and determine the point of deviation from a planar ice interface and ultimately determine the point when the last vestiges of ice disappear. Thereafter, the same characteristics of the time-profile were identified for those TVIS vials located out of sight of the camera in a separate full-shelf lyo study, thereby obviating the need for photographic examination.

本条目收录了我们发表于《Pharmaceutics》（《药剂学》）期刊的研究论文配套图表与原始实验数据。<br>摘要：当前用于冻干瓶内冰升华过程的模型，均假设在冰质量损失约25%之前，冰界面保持平面状态（该假设难以验证）；而通过温度传感器测定单瓶升华终点的方法，则以观测温度达到平台期为依据，但该方法无法区分升华干燥与脱附干燥阶段。本研究中，我们在100 kHz频率下，对升华干燥过程中装有冷冻水的TVIS瓶的电容实部进行了测量。研究表明，该参数对冰团的形状与体积具有极高敏感性，因此可作为监测冰升华过程的有效参数。通过在装有冰的孤立TVIS瓶前方放置数码相机，我们可将冰团形状的变化与电容时间分布曲线的轨迹变化相关联，从而确定冰界面偏离平面状态的临界点，并最终确定冰残余完全消失的时刻。此后，在另一项全搁板冻干研究中，我们对未置于相机视野内的TVIS瓶，同样识别出了其时间分布曲线的特征，从而无需再进行摄影观测。