Thesis-2011-Saleemi.pdf (5.92 MB)
Download fileStrategic feedback control of pharmaceutical crystallization systems
thesis
posted on 2011-06-27, 08:54 authored by Ali N. SaleemiCrystallization is a widely used purification and separation technique in the pharmaceutical
industry. More than 90 % of the active pharmaceutical ingredients are produced in the crystalline
form. The quality of the crystalline product greatly affects the downstream processing and
bioavailability of the drug. The Food and Drug Administration (FDA) initiated in 2004 the use
and implementation of process analytical technology (PAT) in the pharmaceutical development
and production and encourages the pharmaceutical industry to adopt quality by design (QBD)
approaches. The prime objective of this initiative has been to optimize the drug development and
manufacturing process by reducing cost, improving product quality and reducing the number of
failed batches. The work presented in this thesis focuses on expanding the use of two PAT tools,
namely attenuated total reflection ultra violet/visible spectroscopy (ATR-UV/Vis spectroscopy)
and focused beam reflectance measurement (FBRM). ATR-UV/Vis spectroscopy and FRBM are
mostly used for process monitoring. The aim here was to develop sophisticated control
approaches using these in situ tools for enhancing the product quality. Chemometrics is an
integral part of PAT, and can provide valuable information about the system. This tool has also
been used in this study for calibration model development and monitoring the cooling and antisolvent
crystallization processes for single and muticomponent crystallisations.
The development of an accurate and robust calibration model is necessary for qualitative and
quantitative analysis of a system using spectroscopy. A systematic methodology was therefore
presented for the selection of a suitable calibration model for ATR-UV/Vis spectroscopy. The
developed model was then used as part of supersaturation control approach (SSC). SSC uses
information from ATR-UV/Vis spectroscopy in a feedback control loop to keep the system at
desired supersaturation. The developed approach resulted in the production of crystals of uniform
size and can represent the bases for a model-free direct design approach for crystallization
systems. (Continues...).
History
School
- Aeronautical, Automotive, Chemical and Materials Engineering
Department
- Chemical Engineering
Publisher
© Ali Nauman SaleemiPublication date
2011Notes
A Doctoral Thesis. Submitted in partial fulfillment of the requirements for the award of Doctor of Philosophy of Loughborough University.EThOS Persistent ID
uk.bl.ethos.551297Language
- en