Pharmaceuticals with suitable therapeutic properties often found to encounter
challenges with dosage form development due to their poor physicochemical
properties. Aim of thesis is to evaluate potential of crystal engineering directed
cocrystallisation of active ingredients in modulating their physical attributes. The
model compounds considered are isoniazid, caffeine, nifedipine, glyburide,
chlorpropamide and riboflavin. Co-formers selected are based on the suitability
of functional groups for hydrogen bond formation. Co-crystal screening and
preparation methods used include neat grinding (NG), liquid assisted grinding
(LAG) and solution crystallisation.
Antituberculosis drug, isoniazid, upon cocrystallisation with melamine, solubility
has reduced as per high performance liquid chromatography assay, however,
antimicrobial properties determined using REMA assay confirms that cocrystal
anti-mycobacterial activity is not compromised. Next, caffeine-glutaric acid
cocrystal polymorphic forms (Forms I and II) subjected to mechanical property evaluations in multiple faces using nanoindentation and correlated relationship
between crystal structure and mechanical property. The results suggest that
metastable form, Form I, could display suitable tablet properties to that of
thermodynamically stable form, Form II. Subsequently, photosensitive drug,
nifedipine, cocrystallised with theophylline and caffeine. Notably, photochemical
stability along with solubility and drug release of cocrystals is found to be
superior to that of nifedipine. Lastly, crystal engineering principles utilised in
preparation of multicomponent crystals of antidiabetic model drugs, glyburide
and chlorpropamide with various coformers. Interestingly, during the preparation
of chlorpropamide-2-nitrobenzyl alcohol, high Z prime crystal (Z’=3) of 2-
nitrobenzyl alcohol is serendipitously identified. In conclusion, crystal
engineering based cocrystallisation is a viable technology for modulating
physicochemical properties of pharma and nutraceuticals.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/19698 |
| Date | January 2021 |
| Creators | Jhariya, Aditya N. |
| Contributors | Vangala, Venu R., Paradkar, Anant 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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