Tracking raw material flow through a continuous direct compression line Part I of II: Residence time distribution modeling and sensitivity analysis enabling increased process yield.

Int J Pharm

Laboratory of Plant and Process Design, Faculty of Biochemical and Chemical Engineering, TU Dortmund University, Emil-Figge-Straße 70, D-44227 Dortmund, Germany. Electronic address:

Published: February 2022

Continuous manufacturing (CM) offers advantages in quality and space-time yield compared to common batch manufacturing. However, higher yield losses due to the start-up procedure make a broad application uneconomical. This work discusses the possibility of reducing yield losses by adjusting the degree of back-mixing. Back-mixing of nonconforming material from disturbances or start-up will result in the contamination of subsequent material. Therefore, higher degrees of back-mixing cause the discharge of additional material. Choosing an advantageous setting of operational parameters may be a simple way to change the degree of back-mixing. Based on direct compression, this work demonstrates the identification of promising parameters. Therefore, step-change experiments using color-marked material in the feeder, blender, and tablet press quantify the impact of three operational parameters per device. Models for the devices and the entire process result from those measurements. Subsequently, a global variance-based sensitivity analysis identifies the most influential parameters. As a result, adjusting the minimal filling level of the feeder and the rotational feed frame speed of the tablet press reduces back-mixing by more than 30 %. At high costs of the raw materials, the resulting savings can significantly improve the economic performance of CM compared to batch manufacturing.

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Source
http://dx.doi.org/10.1016/j.ijpharm.2022.121467DOI Listing

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