(561g) Implementation of a Dynamic Mechanistic Model Towards Optimal Design and Scale-up of an Atypical Freeze-Drying Process
- Conference: AIChE Annual Meeting
- Year: 2020
- Proceeding: 2020 Virtual AIChE Annual Meeting
- Group: Pharmaceutical Discovery, Development and Manufacturing Forum
- Time: Wednesday, November 18, 2020 - 9:30am-9:45am
This work illustrates process optimization of a previously designed sub-optimal cycle, following a model-based design of experiment approach to minimize the cycle time while meeting the product CQAs. This cycle optimization was unique in that the formulation contained acetic acid and no bulking agent. These atypical formulation components led to a rare freeze-drying cycle optimization opportunity.
A mechanistic, non-steady state process model with a moving boundary (sublimation interface) was used in this work . The cycle time was reduced by 50% (~2.5 days). The process map obtained from the model was used to establish the proven acceptable ranges (PARs) on the critical process parameters and identify the design space. The process was then scaled from lab to pilot plant based on the identified design space. This entire process optimization workflow required less than ~20 grams of the active pharmaceutical ingredient (API) in experimentation.
 Liapis and Bruttini, 1994, A theory for the primary and secondary drying stages of the freeze-drying of pharmaceutical crystalline and amorphous solutes: comparison between experimental data and theory. Sep. Technol., 4, 144-155