Freezing step in lyophilization process: towards a comprehensive lyophilization model and workflow development

11/29/2024

Lyophilization is a technique used to stabilize heat-sensitive substances like active pharmaceutical ingredients (APIs), but it involves high operational costs and stringent quality assurance requirements. The process includes three stages: freezing, primary drying, and secondary drying. Nucleation during freezing is critical, as its stochastic nature can lead to product inconsistencies. This study addresses a gap in the gPROMS software, which currently lacks a model for the freezing step, providing models only for sublimation, primary drying, and secondary drying. The research also aimed to develop web applications for each stage of lyophilization, facilitating easier access to these tools. The freezing models developed predict cooling and freezing times within the cooling and phase change zones. Various models were created, from 0D to 2D dimensions, using heat transfer fundamentals, including the finite difference method and moving boundary models. A 1D model based on the finite difference method was validated with experimental data from a collaboration with AstraZeneca, using an interrupted freezing and sublimation study with water. Heat transfer coefficients were estimated by using results from the sublimation model as input for the freezing model. The 1D model demonstrated strong performance, with process time deviations consistently below 10%, often under 5%, except for slight deviations in the post-phase change zone. These models enhance the understanding of lyophilization, potentially reducing operational costs by providing more accurate predictions of cooling and freezing times. Additionally, the development of web applications for these models promotes wider adoption and usability.

Authors in the community:

• 

  J

  João Henrique Azevedo Ribeiro

  ist196606

Supervisors of this institution:

• 

  C

  Carla Isabel Costa Pinheiro

  ist12547

chemical-engineering - Chemical engineering

por - Portuguese

Instituto Superior Técnico