Freeze-drying of enzymes in case of water-binding and non-water-binding substrates

Enzymes typically have a critical instability, which dominates both formulation and process development. In this paper, the ability to preserve the enzyme activity during freeze-drying was investigated for both water-binding and non-water binding substrates. For this purpose, acid phosphatase was used as model protein. In addition, a procedure for the fast development of a freeze-drying cycle is shown. For the secondary drying part, the effect of processing temperature and time on enzyme activity was investigated. The enzyme activity decreased continuously during secondary drying, with a dramatic drop associated with processing temperatures higher than 293 K. Besides product temperature, the residual moisture level and water mobility are also important. As the residual moisture level and water mobility depend on the product formulation, the stabilizing effect against the enzyme deactivation was studied for a number of formulations which contain different additives, i.e. sucrose, lactose, mannitol, and polyvinylpyrrolidone, with a dramatic activity loss associated with crystallizing excipients. This study also confirmed that not all water-binding substrates can successfully protect the enzyme against deactivation. In fact, water-binding substrates containing reducing sugars (lactose) showed the highest loss of activity

CFD modelling of condensers for freeze-drying processes

The aim of the present research is the development of a computational tool for investigating condensation processes and equipments with particular attention on freeze-dryers. These condensers in fact are usually operated at very low pressures, making it difficult to experimentally acquire quantitative knowledge of all the variables involved. Mathematical modelling and CFD (Computational Fluid Dynamics) simulations are here used to achieve a better comprehension of the flow dynamics and of the process of ice condensation and deposition in the condenser, in order to evaluate condenser efficiency and gain deeper insights on the process to be used for the improvement of its design. Both a complete freeze-drying apparatus of laboratory-scale and an industrial-scale condenser have been investigated in this work, modelling the process of water vapour deposition. Different operating conditions have been considered and the influence exerted by the inert gas as well as other parameters have been investigate