Freeze-Dryer Equipment Capability Limit: Comparison of Computational Modeling With Experiments at Laboratory Scale

• Published in: Journal of pharmaceutical sciences Vol. 108; no. 9; pp. 2972 - 2981
• Main Authors: Shivkumar, Gayathri, Kshirsagar, Vaibhav, Zhu, Tong, Sebastiao, Israel B., Nail, Steven L., Sacha, Gregory A., Alexeenko, Alina A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2019
• Subjects: freeze-drying; lyophilization; quality by design (QBD); thermodynamics; tunable diode laser absorption spectroscopy (TDLAS); thermodynamics; freeze-drying; quality by design (QBD); lyophilization; tunable diode laser absorption spectroscopy (TDLAS)
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1016/j.xphs.2019.04.016

The equipment capability curve is one of the bounding elements of the freeze-drying design space, and understanding it is critical to process design, transfer, and scale-up. The second bounding element of the design space is the product temperature limit beyond which the product collapses. The high cost associated with freeze-drying any product renders it crucial to operate using the most efficient cycle within the limits of the equipment and the product. In this work, we present a computational model to generate the equipment capability curve for 2 laboratory scale freeze-dryers and compare the results to experimentally generated equipment capability curves. The average deviations of the modeling results from the experiments for the 2 lyophilizers modeled are −4.8% and −7.2%. In addition, we investigate the effect of various numerical and geometric parameters on the simulated equipment capability. Among the numerical parameters, the chamber wall thermal boundary conditions exert the largest influence with a maximum value of 12.3%. Among the geometric parameters, the inclusion of the isolation valve reduces the equipment capability by 23.7%. Larger isolation valves, required for controlled nucleation technology, choke the flow in the duct at lower sublimation rates, thereby lowering the equipment capability limit.