The effects of polymer concentration and solvents on cocrystal morphology of
low solubility drugs were investigated, both of which had an impact. The
melting temperatures also decreased with increasing polymer concentration.
Placing the binding agent, benzene, at different interfaces induced
morphological changes, such as formation of porous cocrystals.
Previously liquid-liquid phase separation (LLPS) has been reported as a
hindrance in the crystallisation process impeding further development. A
phase diagram was constructed, and different phases were categorised into 4
types. After separation of the highly concentrated amorphous Oil Phase II, it
was prone to gradual crystallisation. Crystallisation took place over 30-60
minutes; this allowed the in-situ monitoring.
A novel cocrystallisation technique was developed; from (LLPS). Cocrystals of
indomethacin with saccharin and nicotinamide were obtained by mixing Oil
Phase II with the coformers.
In-situ monitoring by spectroscopic had gradual changes in spectra;
characteristic peaks increased in height and area with the formation of crystals
until the reaction was complete. With crystal formation, the XRD spectra
gradually had a sharper baseline due to a decrease in the amorphous
indomethacin. The photoluminescence (PL) spectra displayed several peaks
coupling into one large hump together with increasing intensity as the sample
crystallised. There was a shift in the peak absorbance of the pure drug crystals
obtained from LLPS and the indomethacin:saccharin cocrystal obtained from
LLPS.
Amorphous stabilisation was achieved by mixing polymer (PVP) with Oil
Phase II. There were no changes to the XRD diffractogram as the sample did
not undergo crystallisation.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/18788 |
| Date | January 2019 |
| Creators | Sajid, Muhammad A. |
| Contributors | Paradkar, Anant R, Kelly, Adrian L., Vangala, Venu R. |
| Publisher | University of Bradford, Faculty of Life Sciences |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Thesis, doctoral, PhD |
| Rights | <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>. |
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