The crystalline solid state is invaluable to both the pharmaceutical and fine chemical sectors. The
advantages primarily relate to reducibility criteria required during processing of stable solid state
materials and delivering purification, which is inherently performed by the crystal growth process. A
major challenge is achieving control through crystallising solids with the desired physico-chemical
properties. If this can be achieved the crystalline solid is of great financial and practical benefit. One
emerging methodology for manipulating the solid crystalline form is the application of co-crystals.
This work relates to key steps in the understanding of rational design of co-crystals utilizing crystal
engineering concepts to determine systems before then applying screening criteria to the selected
sub-set. Co-crystal screening is routinely undertaken using high-throughput solution growth. We
report a low- to medium-throughput approach, encompassing both a melt and solution crystallization
step as a route to the identification of co-crystals. Prior to solution studies, a melt growth step was
included utilizing the Kofler mixed fusion method. This method allowed elucidation of the
thermodynamic landscape within the binary phase diagram and was found to increase overall
screening efficiency. This led to the discovery of a number of co-crystal systems with the co-former
nicotinamide, with the single crystal structures determined for the following systems; R/S ibuprofen:
nicotinamide, S ibuprofen: nicotinamide, R/S flurbiprofen: nicotinamide and salicylic acid:
nicotinamide.
To assess the crystallization and phase behaviours of determined co-crystals the R/S ibuprofennicotinamide
system was selected and successful studies were undertaken determining the aqueous
ternary phase behavior and the pre-nucleation speciation in methanol. There have, as yet, been a
limited number of published examples which are concerned with pharmaceutical property
enhancement by co-crystals, as vast proportion of the literature concerns the growth and isolation of
these novel phases. To elucidate further the pharmaceutical relevance of co-crystals the properties
of the R/S ibuprofen- nicotinamide system were then assessed showing a positive profile for this
material. / AstraZeneca and the University of Bradford / The accompanying "Experimental raw data files and cifs" are not available online.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/4932 |
| Date | January 2009 |
| Creators | Berry, David J. |
| Contributors | Blagden, Nicholas, Storey, Richard |
| Publisher | University of Bradford, School of pharmacy |
| 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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