<div>
<p>Guided by the continuous manufacturing
paradigm shift in the pharmaceutical industry, the proposed thesis focuses on
the implementation of an integrated continuous crystallization platform, the
oscillatory baffled crystallizer (OBC), with real time process monitoring.
First, by defining an appropriate operating regime with residence time distribution
(RTD) measurements, a system can be defined that allows for plug flow operation
while also maintaining solid suspension in a two-phase system. The aim of
modern crystallization processes, narrow crystal size distributions (CSDs), is
a direct result of narrow RTDs. Using a USB microscope camera and principal
component analysis (PCA) in pulse tracer experiments, a novel non-contact RTD
measurement method was developed using methylene blue. After defining an
operating region, this work focuses on a specific process intensification
technique, namely spherical crystallization.</p>
<p>Used mainly to
tailor the size of a final dosage form, spherical crystallization removes the
need for downstream size-control based unit operations (grinding, milling, and
granulation), while maintaining drug efficacy by tailoring the size of the
primary crystals in the agglomerate. The approach for generating spherical
agglomerates is evaluated for both small and large molecules, as there are
major distinctions in process kinetics and mechanisms. To monitor the spherical
agglomeration process, a variety of Process Analytical Technology (PAT) tools
were used and the data was implemented for scale-up applications.</p>
<p>Lastly, a
compartmental model was designed based on the experimental RTD data with the
intention of predicting OBC mixing and scale-up dynamics. Together, with
validation from both the DN6 and DN15 systems, a scale independent equation was
developed to predict system dispersion at different mixing conditions. Although
it accurately predicts the behavior of these two OBC systems, additional OBC
systems of different scale, but similar geometry should be tested for
validation purposes.</p>
</div>
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| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/7993940 |
| Date | 15 May 2019 |
| Creators | Joseph A Oliva (6588797) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/Process_Intensification_Techniques_for_Continuous_Spherical_Crystallization_in_an_Oscillatory_Baffled_Crystallizer_with_Online_Process_Monitoring/7993940 |
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