The purpose of this paper is to revisit the design of three steps in the freeze-drying process: freezing, primary drying, and secondary drying. Specifically, it provides up-to-date recommendations for selecting freeze-drying conditions based on the physical-chemical properties of formulations and engineering considerations.
This paper discusses fundamental factors to consider when selecting freezing, primary drying, and secondary drying conditions. It offers mathematical models to predict the duration of each segment and the product temperature during primary drying. Three simple heat/mass transfer primary drying (PD) models were tested, and they demonstrated good agreement in predicting product temperature and sublimation time. These PD models were validated based on experimental data and used to tabulate primary drying conditions for common pharmaceutical formulations, including amorphous and partially crystalline products. Examples of calculated drying cycles, encompassing all steps, are provided for typical amorphous and crystalline formulations.
The authors revisited advice from a seminal paper by Tang and Pikal (Pharm Res. 21(2):191-200, 2004) on selecting freeze-drying process conditions and found that the majority of recommendations are still applicable today. Several advancements, including methods to promote ice nucleation and computer modeling for all steps of the freeze-drying process, have been made. The authors have created a database for primary drying and provided examples of complete freeze-drying cycle designs. This paper can supplement the knowledge of scientists and formulators and serve as a user-friendly tool for quickly estimating the design space.
Thank you to the authors: Serguei Tchessalov (Pfizer), Vito Maglio (Purdue University), Petr Kazarin (Purdue University), Alina Alexeenko (Purdue University), Bakul Bhatnagar (Pfizer), Ekneet Sahni (Regeneron), and Evgenyi Shalaev (AbbVie) for your hard work and dedication to this project.
Download the paper here: https://link.springer.com/article/10.1007/s11095-023-03607-9