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|Title: ||Toward continuous crystallization of Urea-Barbituric acid: a polymorphic co-crystal system|
|Authors: ||Powell, Keddon A.|
Wittering, Kate E.
Saleemi, Ali N.
Wilson, Chick C.
Rielly, Chris D.
Nagy, Zoltan K.
|Issue Date: ||2015|
|Publisher: ||© American Chemical Society|
|Citation: ||POWELL, K.A., 2015. Toward continuous crystallization of Urea-Barbituric acid: a polymorphic co-crystal system. Crystal Growth and Design, 15(10), pp 4821–4836.|
|Abstract: ||Pharmaceutical co-crystals are multicomponent molecular systems typically formed through hydrogen bonding of a co-former molecule with the active pharmaceutical ingredient (API). Just as many
single component molecular structures can exhibit polymorphism due to the geometry of hydrogen bond donors and acceptors, the same is true for pharmaceutical co-crystals. In this study, the selective cocrystallization
of the desired polymorphic form of urea-barbituric acid (UBA) co-crystals (forms I and III) is demonstrated, applying a novel periodic mixed suspension mixed product removal (PMSMPR)
crystallizer cascade. The process was monitored using an integrated process analytical technology (PAT) array consisting of Raman spectroscopy, attenuated total reflectance ultraviolet/visible (ATRUV/
vis) spectroscopy, focused beam reflectance measurement (FBRM), particle vision microscopy (PVM), and an in-house
developed commercial crystallization process informatics system (CryPRINS) software tool to determine when a “state of controlled operation” (SCO) was achieved. Three different start-up strategies were employed and their ability to produce selectively a particular polymorphic form of UBA was evaluated. The experimental conditions for producing pure UBA form I were optimized, but pure UBA form III remained elusive. Off-line characterization of the UBA polymorphs was carried out using Powder X-ray Diffraction (PXRD) and Raman spectroscopy.|
|Description: ||This paper is in closed access until 2nd Sept 2016.|
|Sponsor: ||This paper was funded by the EPSRC (EP/I033459/1) and the Centre for Continuous Innovation in Continuous Manufacturing and Crystallization (CMAC) for the financial
support of this work and the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. [280106-CrySys] (for equipment and financial support).|
|Version: ||Accepted for publication|
|Publisher Link: ||http://dx.doi.org/10.1021/acs.cgd.5b00599|
|Appears in Collections:||Closed Access (Chemical Engineering)|
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