Long_2019_Controlling.pdf (1.6 MB)
Controlling polymorphism of carbamazepine nanoparticles in a continuous supercritical-CO2-assisted spray drying process
journal contribution
posted on 2019-09-26, 10:32 authored by Barry Long, Gavin M. Walker, KEVIN M. RYANKEVIN M. RYAN, Luis PadrelaLuis PadrelaControlling polymorphism in the transition from batch to continuous crystallization represents
a major obstacle for the pharmaceutical industry. This work demonstrates a novel methodology
to control the polymorphism of carbamazepine (CBZ) nanoparticles, a highly polymorphic
BCS class II drug, using a continuous supercritical CO2 antisolvent-assisted nano spray drying
(SASD) process. We show herein that when supersaturation conditions are achieved in the
high-pressure SASD nozzle in the presence of anionic additives (e.g. sodium stearate, sodium
dodecyl sulfate), nanoparticles of the metastable CBZ form II (using sodium stearate) or the
stable CBZ form III (using sodium dodecyl sulfate) are obtained from methanol solutions,
respectively. This novel methodology provides control over the final polymorphic form of CBZ
obtained by (1) templating the desired polymorphic form when supercritical CO2 supersaturates
the CBZ-additive methanol solution in the nozzle and (2) avoiding/minimizing the occurrence
of any possible polymorphic transformation by immediately spray drying the supercritical
antisolvent induced suspension into a dried fine powder. These results contrast with those
obtained when using non-supersaturating conditions in the SASD nozzle (amorphous CBZ is
obtained, regardless of the additive used) and when using conventional spray drying (SD)
where there is no antisolvent effect in the nozzle (CBZ form IV is obtained, regardless of the
additive used). The impact that the mass ratio of methanol and supercritical CO2 has on the
supersaturation and consequently on the polymorphic outcome of carbamazepine obtained
from batch and continuous supercritical CO2 antisolvent crystallization processes is also
discussed.
Funding
Study on Aerodynamic Characteristics Control of Slender Body Using Active Flow Control Technique
Japan Society for the Promotion of Science
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Publication
Crystal Growth and Design;19 (7), pp. 3755-3767Publisher
American Chemical SocietyNote
peer-reviewedOther Funding information
SFI, ERCRights
© 2019 ACS This document is the Accepted Manuscript version of a Published Work that appeared in final form in Crystal Growth and Design, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see htttp://dx.doi.org/10.1021/acs.cgd.9b00154Language
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