5 research outputs found
Toward Continuous Crystallization of Urea-Barbituric Acid: A Polymorphic Co-Crystal System
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 co-crystallization
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 (ATR-UV/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