Optimal design of crystallization processes for the recovery of a slow-nucleating sugar with a complex chemical equilibrium in aqueous solution: The case of lactose

Lactose is the major carbohydrate in milk, and similarly to other sugars, it can exist as two anomers in solution, the α and β forms, with a ratio depending on factors including temperature and pH (mutarotation equilibrium). Lactose is extracted from whey mostly to prevent environmental pollution. In fact, the presence of this sugar can contribute to a dramatic increase in the biological oxygen demand (BOD) of whey, making its direct disposal potentially dangerous for the environment. However, preserving our ecosystem is not the only reason why lactose is recovered. Purified lactose is in fact a high-value product that is commonly used as an excipient in pharmaceutical formulations and as a carrier in dry-powder inhalers. Despite the increasing interest that lactose crystallization has recently received, a full understanding of this process is still missing, particularly the link between the process parameters of the crystallization step and the properties of the final product in terms of crystalline structure, purity, and particle size and shape distributions. To the authors’ knowledge, this work is the most comprehensive study of lactose crystallization reported to date, exploring cooling and antisolvent operations to determine the effect of several operative conditions on (i) the kinetics of nucleation, growth, and agglomeration; (ii) the yield of lactose recovery from solution; (iii) the final crystal size and shape distributions; and (iv) the purity of the obtained crystals.