A Model-Based Framework to Optimize Pharmaceuticals Freeze Drying

Abstract

This article is focused on the design of pharmaceutical freeze-drying recipes using in-line or off-line tools. In particular, the model predictive control system is here used to optimize the in-line process, and the design space is used for off-line optimization. Because both methods uses a mathematical model of the process, the problem of estimating the model parameters, including their uncertainty or variability in the lot of vials, is addressed. Then, the strengths and the weaknesses of the various methods are discussed, with particular emphasis on their robustness and their application in industrial-scale freeze dryers. In particular, the ability of the model predictive control tool to obtain the optimal recipe in only one run and its capacity to manage the system in case of an in-line modification of the product properties are shown. For this purpose, experimental results obtained for sucrose- and mannitol-based formulations are presented.

Keywords:

• Design space
• Mannitol
• Mass transfer resistance
• Mathematical modeling
• Model predictive control
• Process analytical technology
• Sucrose

ACKNOWLEDGMENTS

The contributions of Giovanni Accardo and Alberto Vallan (Politecnico di Torino) to the experimental investigation and the setup of the weighing device, respectively, are gratefully acknowledged.