(107d) Continuous Distillation Operations and Application of the Wiped Film Evaporator (WFE) to Pharmaceutical Pilot Plant Processing

Authors: 
Mohan, A. E., Merck & Co., Inc.
Fisher, E., Merck & Co., Inc.
Hennessey, R., Merck & Co., Inc.
Lashen, D., Merck & Co., Inc.
Miranda, C., Merck & Co., Inc.
Spencer, G., Merck and Co. Inc.
Ward, M., Merck & Co., Inc.
Yue, M., Merck & Co., Inc.
Zhou, G., Merck & Co., Inc.


The utilization of continuous processing technology provides increased productivity and versatility to scaled processes.  Continuous distillation technology, in addition to providing these general benefits, provides the opportunity to process streams at higher temperatures and lower pressure ranges than batchdistillation operations.  Wiped film evaporation (hereafter referred to as "WFE"), which is a type of continuous distillation technology, is ideal for heat sensitive and/or high-boiling products due to the short residence time (less than 60 sec) and the low vacuum capability (down to ~1 mm Hg) of the unit.  In addition, the volume of batch required for WFE operation is significantly less that that required for batch distillation, making WFE appropriate for low-volume products.  Wiped film evaporation (WFE) is a type of continuous distillation technology recently investigated, developed, and ultimately applied to a pharmaceutical project at the Merck Rahway site at the pilot plant scale.  This technology was utilized in order to address the thermal instability and high boiling issues associated with a specific process.  The data gathered from this operations was analyzed in order to understand and characterize the heat transfer of the WFE unit and the batch performance in the WFE.  Additionally, the data was used to develop a scaling procedure which can be applied to take a process from the lab to the pilot plant scale.  The experiments used to accomplish these tasks explored the controllable variables of the WFE unit, such as feed rate, wiper speed, pressure, and temperature.  The implementation of wiped film evaporation to this process is an example of the appropriate application of continuous distillation technology at scale, and the benefits of such an application.

The objective of this presentation is to communicate and discuss the recent lab development and pilot plant work with wiped film evaporation technology, which is used for continuous distillation processing.  The presentation will focus on the methodology used to scale-up the technology, the challenges faced in the pilot plant, how these challenges were handled, and the accomplishments of the campaign both in the lab and in the pilot plant.  The presentation will provide: (1) an in-depth overview of the wiped film evaporation operation, (2) a detailed description of the data collected and knowledge gained by all WFE units, with specific focus on the larger 6'' unit, (3) a list of the advantages and disadvantages observed through the operation of all size WFE units, and (4) a report of the quantitative and qualitative results of the WFE usage for the batch processing.  The technological and process-specific knowledge that was gained through the Merck WFE experiences can be used to promote the continuous platform.

See more of this Session: Pharmaceutical Process Development & Pilot Plants

See more of this Group/Topical: Process Development Division