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Keywords:

  • lyophilization;
  • freeze-drying;
  • protein formulation;
  • proteins;
  • microscopy

Abstract

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 (Tc) 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 Tc of formulations in pharmaceutically relevant products containers (i.e., freeze-drying in vials). OCT–FDM was used to measure the Tc and eutectic melt of three formulations in freeze-drying vials. The Tc 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 Tc measured by LT-FDM and provides a reliable upper limit to setting a product temperature in primary drying. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1773–1785, 2013