Application of continuous crystallization in an integrated continuous pharmaceutical pilot plant

TitleApplication of continuous crystallization in an integrated continuous pharmaceutical pilot plant
Publication TypeJournal Article
Year of Publication2014
AuthorsZhang H, Lakerveld R, Heider PL, Tao M, Su M, Testa C, D'Antonio A, Barton PI, Braatz RD, Trout BL, Myerson AS, Jensen KF, Evans JMB
JournalCrystal Growth and Design
Volume14
Issue5
Pagination2148–2157
Date Published03/2014
Abstract

Real-time control using Process Analytical Technology (PAT) tools is required for the implementation of continuous crystallization within Integrated Continuous Manufacturing (ICM) of pharmaceuticals. However, appropriate selection of PAT tools is challenging and the design and operation of automated control loops for continuous crystallization within a continuous pharmaceutical process brings forward important questions. This paper describes the process design and operation of a continuous reactive crystallization of aliskiren hemifumarate as part of an ICM pilot plant. Several PAT tools were used within automated control loops to satisfy specifications on the critical materials attributes of the crystallization process. The operational performance of the process was maintained for periods of time over 100 hours. The purity of the targeted product exceeded 99% and the process yield reached 91.4%.

URLhttp://pubs.acs.org/doi/abs/10.1021/cg401571h
DOI10.1021/cg401571h