Analysis of the Effects of Process Parameters on Start-Up Operation in Continuous Wet Granulation

Kensaku Matsunami,Alexander Ryckaert,Ingmar Nopens,Thomas De Beer,Hirokazu Sugiyama,Michiel Peeters,Sara Badr

doi:10.3390/pr9091502

Kensaku Matsunami, Alexander Ryckaert + Show 5 more

Open Access

https://doi.org/10.3390/pr9091502

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Journal: Processes	Publication Date: Aug 25, 2021
Citations: 9	License type: CC BY 4.0

Affiliation: The University of Tokyo, Ghent University

Abstract

Toward further implementation of continuous tablet manufacturing, one key issue is the time needed for start-up operation because it could lead to lower product yield and reduced economic performance. The behavior of the start-up operation is not well understood; moreover, the definition of the start-up time is still unclear. This work investigates the effects of process parameters on the start-up operation in continuous wet granulation, which is a critical unit operation in solid drug manufacturing. The profiles of torque and granule size distribution were monitored and measured for the first hour of operation, including the start-up phase. We analyzed the impact of process parameters based on design of experiments and performed an economic assessment to see the effects of the start-up operation. The torque profiles indicated that liquid-to-solid ratio and screw speed would affect the start-up operation, whereas different start-up behavior resulted in different granule size. Depending on the indicator used to define the start-up operation, the economic optimal point was significantly different. The results of this study stress that the start-up time differs according to the process parameters and used definition, e.g., indicators and criteria. This aspect should be considered for the further study and regulation of continuous manufacturing.

Highlights

Continuous manufacturing has been introduced as an alternative to conventional batch in tablet manufacturing processes [1]
The start-up time is defined as that when the process stabilizes, this work has shown that this could differ between process variables, such as torque, and product response variables, such as granule size
One interesting aspect that emerged from the analysis is the difference in the response at the start-up operation between torque and granule size distribution

Summary

Introduction

Continuous manufacturing has been introduced as an alternative to conventional batch in tablet manufacturing processes [1]. In batch-wise manufacturing, each unit operation is performed separately with a certain lot size, e.g., 100 kg. Researchers have discussed the benefits of continuous manufacturing from various perspectives, e.g., flexibility to demand change, less need for scale-up, and compatibility with process control [2,3]. For further application of continuous manufacturing, various technical and regulatory challenges still exist. Process parameters need to be well defined, which could be more difficult in continuous manufacturing. Due to the nature of operation, the definition of lot size is different from that in batch manufacturing and has yet to be fully fixed [24]. Lot size definition is critical because it affects other challenges, e.g., material traceability and control strategy [24]

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