Skip to main content
Trending this week: Beyond RTRt Models: The Hidden Challenges of Implementation

A NIR-Based Study of Desorption Kinetics during Continuous Spin Freeze-Drying

By Leys, Laurens; Nuytten, Gust; Lammens, Joris; Van Bockstal, Pieter-Jan; Corver, Jos; Vervaet, Chris; De Beer, Thomas

Published on CMKC


The pharmaceutical industry is progressing toward the development of more continuous manufacturing techniques. At the same time, the industry is striving toward more process understanding and improved process control, which requires the implementation of process analytical technology tools (PAT). For the purpose of drying biopharmaceuticals, a continuous spin freeze-drying technology for unit doses was developed, which is based on creating thin layers of product by spinning the solution during the freezing step. Drying is performed under vacuum using infrared heaters to provide energy for the sublimation process. This approach reduces drying times by more than 90% compared to conventional batch freeze-drying. In this work, a new methodology is presented using near-infrared (NIR) spectroscopy to study the desorption kinetics during the secondary drying step of the continuous spin freeze-drying process. An inline PLS-based NIR calibration model to predict the residual moisture content of a standard formulation (i.e., 10% sucrose) was constructed and validated. This model was then used to evaluate the effect of different process parameters on the desorption rate. Product temperature, which was controlled by a PID feedback mechanism of the IR heaters, had the highest positive impact on the drying rate during secondary drying. Using a higher cooling rate during spin freezing was found to significantly increase the desorption rate as well. A higher filling volume had a smaller negative effect on the drying rate while the chamber pressure during drying was found to have no significant effect in the range between 10 and 30 Pa.


Pharmaceutics. Volume 13, 12, 2021, 2168



Type of publication

Peer-reviewed journal


  • Ghent University

Article Classification

Research article

Classification Areas

  • Oral solid dose