A New Model-Based Approach for the Development of Freeze-Drying Cycles Using a Small-Scale Freeze-Dryer

This paper presents a model-based approach for the design of the primary drying stage of a freeze-drying process using a small-scale freeze-dryer (MicroFD® by Millrock Technology Inc.). Gravimetric tests, coupled with a model of the heat transfer to the product in the vials that account also for the heat exchange between the edge vials and the central vials, are used to infer the heat transfer coefficient from the shelf to the product in the vial (K_v), that is expected to be (almost) the same in different freeze-dryers. Differently from other approaches previously proposed, the operating conditions in MicroFD® are not chosen to mimic the dynamics of another freeze-dryer: this allows saving time and resources as no experiments are needed in the large-scale unit, and no additional tests in the small-scale unit, apart from the three gravimetric tests usually needed to assess the effect of chamber pressure on K_v. With respect to the other model parameter, R_p, the resistance of the dried cake to mass transfer, it is not influenced by the equipment and, thus values obtained in a freeze-dryer may be used to simulate the drying in a different unit, provided the same filling conditions are used, as well as the same operating conditions in the freezing stage, and cake collapse (or shrinkage) is avoided. The method was validated considering ice sublimation in two types of vials (2R and 6R) and at different operating conditions (6.7, 13.3 and 26.7 Pa), with the freeze-drying of a 5% w/w sucrose solution as a test case. An accurate estimate for both K_v and R_p was obtained with respect to the values obtained in a pilot-scale equipment, determined through independent tests for validation purposes. Simulation of the product temperature and drying time in a different unit was then possible, and results were validated experimentally.