Insulin Wave Dynamics in Size-Exclusion Simulated Moving Bed with Residence Time Control

In the application of simulated moving bed (SMB) technology to a pharmaceutical purification, the residence time of a product inside the SMB should be shortened, to prevent possible aggregation or denaturation. In addition, each key concentration wave should be confined in an appropriate zone to maintain high yield and high purity throughout the SMB operation. To achieve both goals, one must first understand clearly dynamic wave propagation phenomena in connection with solute residence time in the SMB. For this purpose, a series of transient column profiles in the tandem SMB for insulin purification are generated from computer simulations based on a detailed rate model. The column profiles show that the insulin molecules take a long time to reach the product port if they stay in the zone where the insulin wave is standing (or the standing zone). This leads to a long residence time. To shorten the insulin residence time, one can reduce the amount of insulin in the standing zone or modify the zone flow rates such that the insulin wave becomes focused or pinched. The former can be realized by a partial feeding strategy and the latter by a pinched wave design (PWD) method. The wave propagation phenomena for each case are shown using a series of insulin column profiles from the rate model simulations. Based on the understanding of the insulin wave dynamics, a three-zone SMB based on the PWD condition is proposed as the most effective strategy to reduce the residence time of insulin.