Averaging Level Control to Reduce Off-Spec Material in a Continuous Pharmaceutical Pilot Plant

Processes

Richard Lakerveld¹  Brahim Benyahia¹  Patrick L. Heider²  Haitao Zhang²  Richard D. Braatz² 

[1] Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA;

关键词: control;    process modeling;    process simulation;    parameter estimation;    dynamic modeling;    optimization;    crystallization;    continuous pharmaceutical manufacturing;   

DOI  :  10.3390/pr1030330

来源: mdpi

【 摘 要 】

The judicious use of buffering capacity is important in the development of future continuous pharmaceutical manufacturing processes. The potential benefits are investigated of using optimal-averaging level control for tanks that have buffering capacity for a section of a continuous pharmaceutical pilot plant involving two crystallizers, a combined filtration and washing stage and a buffer tank. A closed-loop dynamic model is utilized to represent the experimental operation, with the relevant model parameters and initial conditions estimated from experimental data that contained a significant disturbance and a change in setpoint of a concentration control loop. The performance of conventional proportional-integral (PI) level controllers is compared with optimal-averaging level controllers. The aim is to reduce the production of off-spec material in a tubular reactor by minimizing the variations in the outlet flow rate of its upstream buffer tank. The results show a distinct difference in behavior, with the optimal-averaging level controllers strongly outperforming the PI controllers. In general, the results stress the importance of dynamic process modeling for the design of future continuous pharmaceutical processes.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.