Numerical and experimental modeling of lyophilization of lactose and mannitol water solitions in vials

Abstract

The paper reports on the development of a numerical model for the simulation of a liofilization process in a vial. The lactose and mannitol-water mixtures are used as the working medium in the vial. Experimental analysis of lyofilization dynamics inside a single vial and multiple vials in a laboratory scale lyofilizer is reported, with the main focus on the primary drying phase. The key parameter measured is the temperature distribution inside the main axis of the vial filling. In the numerical model, a 1D vial approximation is used, and governing equations of heat and water vapor transport with moving front between the frozen and the porous part of the filling are solved by a dedicated finited difference method in a time stepping nonlinear iteration procedure. The comparison of numerical and experimental results show, that the developed numerical model is able to accurately capture the transition points from primary to secondary drying, accompanied by accurate capturing of the temperature levels inside the drying material. The main difference in drying of lactose and mannitol solutions lies in the fact, that the lactose shows undercooling effects during the primary drying phase, which is not the case for the mannitol solution. This effect is a consequence of shrinking behavior of lacose porous matrix, loosing contact with vial side and hence decreasing the overall heat input to the vial. The derived numerical model is able to accurately reproduce drying kinetics of mannitol, whereas for drying of lactose an upgrade of the model to axysimmetric geometry would be needed.