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A novel solvent-free high shear technology for the preparation of pharmaceutical cocrystals
Mohammed, Azad F.
Mohammed, Azad F.
Publication Date
2020
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The University of Bradford theses are licenced under a Creative Commons Licence.
Peer-Reviewed
Open Access status
Accepted for publication
Institution
University of Bradford
Department
Faculty of Life Sciences
Awarded
2020
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Abstract
High shear melt granulation (HSMG) is an established technology for a production
of densified granules. In this project, it was used as a novel solvent-free method
for the preparation of cocrystals. Cocrystals produced by HSMG were compared
to those prepared by Hot Melt Extrusion (HME) to investigate the influence of
variable parameters and conditions on the process of cocrystal conversion. The
potential for the active control of cocrystals polymorphism utilising the intrinsic
properties of lipids was also investigated in this project. Different cocrystal pairs
were prepared by both cocrystallisation methods using glycol derivative polymers.
Thermal analysis, powder X-ray diffraction and Raman spectroscopy were used
as analytical techniques to determine the cocrystal yield and purity.
The results obtained from HSMG suggest that sufficient binder concentrations
(above 12.5% w/w) in a molten state and continuous shearing force are necessary
to achieve a complete cocrystals conversion. Further increase in binder
concentration (15% w/w) was found to provide more regular shape and smooth
surface to the prepared spherical granules. Cocrystals preparation by HME was achievable after introducing a mixing zone to the extruder configuration (Conf B
and Conf C) providing densified extrudates containing pure cocrystals.
In conclusion, HSMG was found as a versatile technique for the preparation of
pure pharmaceutical cocrystals embedded in polymer matrix within a spherical
shape granule of smooth surfaces, providing additional desirable characteristics.
Intensive surface interaction, enhanced by sufficient mixing under optimal
parameters, was found as a key influencing factor in cocrystallisation. Cocrystals
polymorphism was actively controlled by employing the intrinsic properties of
polymers and lipids.
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Type
Thesis
Qualification name
PhD