Accurate Prediction of Collapse Temperature using Optical Coherence Tomography-Based Freeze-Drying Microscopy

The objective of this study was to assess the feasibility of developing and applying a laboratory tool that can provide three-dimensional product structural information during freeze-drying and which can accurately characterize the collapse temperature (T_c) of pharmaceutical formulations designed for freeze-drying. A single-vial freeze dryer coupled with optical coherence tomography freeze-drying microscopy (OCT–FDM) was developed to investigate the structure and T_c of formulations in pharmaceutically relevant products containers (i.e., freeze-drying in vials). OCT–FDM was used to measure the T_c and eutectic melt of three formulations in freeze-drying vials. The T_c as measured by OCT–FDM was found to be predictive of freeze-drying with a batch of vials in a conventional laboratory freeze dryer. The freeze-drying cycles developed using OCT–FDM data, as compared with traditional light transmission freeze-drying microscopy (LT-FDM), resulted in a significant reduction in primary drying time, which could result in a substantial reduction of manufacturing costs while maintaining product quality. OCT–FDM provides quantitative data to justify freeze-drying at temperatures higher than the T_c measured by LT-FDM and provides a reliable upper limit to setting a product temperature in primary drying.