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Applications of ultrasound in pharmaceutical processing and analytics.

Apshingekar, Prafulla P.
Publication Date
2014
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Supervisor
Paradkar, Anant R
Kelly, Adrian L.
Brown, Elaine
Keywords
High power ultrasound, Co-crystallisation, Process analytical technology, In-line ultrasound monitoring, Pharmaceutical processing
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Creative Commons License
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
Centre for Pharmaceutical Engineering Sciences, Faculty of Life Sciences
Awarded
2014
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PhD Thesis
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Abstract
Innovations and process understanding is the current focus in pharmaceutical industry. The objective of this research was to explore application of high power ultrasound in the slurry crystallisation and application of low power ultrasound (3.5 MHz) as process analytical technology (PAT) tool to understand pharmaceutical processing such as hot melt extrusion. The effect of high power ultrasound (20 kHz) on slurry co-crystallisation of caffeine / maleic acid and carbamazepine / saccharin was investigated. To validate low power ultrasound monitoring technique, it was compared with the other techniques (PAT tools) such as in-line rheology and in-line NIR spectroscopy. In-line rheological measurements were used to understand melt flow behaviour of theophylline / Kollidon VA 64 system in the slit die attached to the hot melt extruder. In-line NIR spectroscopic measurements were carried out for monitoring any molecular interactions occurring during extrusion. Physical mixtures and the processed samples obtained from all experiments were characterised using powder X-ray diffraction, thermogravimetry analysis, differential scanning calorimetry, scanning Electron Microscopy, dielectric spectroscopy and high performance liquid chromatography, rotational rheology, fourier transform infrared spectroscopy and near infrared spectroscopy. The application of high power ultrasound in slurry co-crystallisation of caffeine / maleic acid helped in reducing equilibrium time required for co-crystal formation. During carbamazepine / saccharin co-crystallisation high power ultrasound induced degradation of carbamazepine was negligible. Low power ultrasound can be used as a PAT tool as it was found to be highly sensitive to the changes in processing temperatures and drug concentration.
URI
http://hdl.handle.net/10454/14127
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Type
Thesis
Qualification name
PhD
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