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Investigation of a solvent-free continuous process to produce pharmaceutical co-crystals. Understanding and developing solvent-free continuous cocrystallisation (SFCC) through study of co-crystal formation under the application of heat, model shear and twin screw extrusion, including development of a near infrared spectroscopy partial least squares quantification method
Wood, Clive John
Wood, Clive John
Publication Date
2016
End of Embargo
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The University of Bradford theses are licenced under a Creative Commons Licence.
Peer-Reviewed
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Accepted for publication
Institution
University of Bradford
Department
School of Life Sciences
Awarded
2016
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Abstract
This project utilised a novel solvent-free continuous cocrystallisation (SFCC)
method to manufacture pharmaceutical co-crystals. The objectives were to
optimize the process towards achieving high co-crystal yields and to
understand the behaviour of co-crystals under different conditions. Particular
attention was paid to the development of near infrared (NIR) spectroscopy as
a process analytical technology (PAT).
Twin screw, hot melt extrusion was the base technique of the SFCC process.
Changing parameters such as temperature, screw speed and screw
geometry was important for improving the co-crystal yield. The level of
mixing and shear was directly influenced by the screw geometry, whilst the
screw speed was an important parameter for controlling the residence time
of the material during hot melt extrusion. Ibuprofen – nicotinamide 1:1 cocrystals
and carbamazepine – nicotinamide 1:1 co-crystals were successfully
manufactured using the SFCC method.
Characterisation techniques were important for this project, and NIR
spectroscopy proved to be a convenient, accurate analytical technique for
identifying the formation of co-crystals along the extruder barrel. Separate
thermal and model shear deformation studies were also carried out to
determine the effect of temperature and shear on co-crystal formation for
several different pharmaceutical co-crystal pairs.
Finally, NIR spectroscopy was used to create two partial least squares
regression models, for predicting the 1:1 co-crystal yield of ibuprofen –
nicotinamide and carbamazepine – nicotinamide, when in a powder mixture
with the respective pure API. It is believed that the prediction models created
in this project can be used to facilitate future in-line PAT studies of
pharmaceutical co-crystals during different manufacturing processes.
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Type
Thesis
Qualification name
PhD