Structural studies of organic crystals of pharmaceutical relevance. Correlation of crystal structure analysis with recognised non-bonded structural motifs in the organic solid state
Thesis-Abstract,table of contents.pdf (338.2Kb)Download
Thesis introduction-chapter one.pdf (483.8Kb)Download
Thesis-experimental-chapter 2.pdf (197.5Kb)Download
Chalcones-chapter 3.pdf (1.147Mb)Download
cryptolepines -chapter 4.pdf (1.108Mb)Download
Biguanides-chapter 5.pdf (1.088Mb)Download
xanthines-chapter 6.pdf (1.503Mb)Download
CONCLUSION -chapter 7.pdf (47.30Kb)Download
Thesis-Appendix-A,B and C.pdf (239.4Kb)Download
INFRA_RED-Appendix D.pdf (981.8Kb)Download
PXRD-Appendix E.pdf (1.071Mb)Download
Raman-Appendix F.pdf (776.0Kb)Download
Mass Spec-Appendix G.pdf (302.6Kb)Download
NMR-Appendix H.pdf (2.749Mb)Download
SupervisorScowen, Ian J.
Edwards, Howell G.M.
KeywordSingle crystal structure
; Structural motifs
; Pharmaceutical solids
; Physico-chemical stability
; Crystallization studies
Rights© 2009 Essandoh, E. This work is licensed under a Creative Commons Attribution-Non-Commercial-Share-Alike License (http://creativecommons.org/licenses/by-nc-nd/2.0/uk).
InstitutionUniversity of Bradford
DepartmentSchool of Pharmacy
MetadataShow full item record
AbstractPharmaceutical solids tend to exist in different physical forms termed as polymorphs. Issues about pharmaceutical systems are mainly concerned with the active ingredient's physico-chemical stability and bioavailability. The main aim of this study is to investigate the non-bonded interactions in pharmaceutical solids that govern the physical pharmaceutics performance of such materials and through the use of structural techniques and correlation of these results with crystal structural database to establish the presence of physical motifs in selected systems. Structural motifs were identified by the use of single crystal and crystal packing analysis on diverse range of pharma-relevant materials including chalcones, cryptolepines, biguanides and xanthines. These selected systems were validated using functional group and molecular analysis and correlating them to the Cambridge Structural Database. Crystallization studies are done on these selected systems as well as exploiting those using synthetic analogues. A total of 51 crystal structures were investigated including 16 new structure determinations. Addition synthesis of new xanthines to investigate novel intermolecular patterns was also undertaken. The understanding and exploitation of intermolecular interactions involving hydrogen bonds and coordination complexation during packing can be used in the design and synthesis of solid state molecular structures with desired physical and chemical properties.
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A Perimetric Test Procedure That Uses Structural InformationGaneshrao, S.B.; McKendrick, A.M.; Denniss, Jonathan; Turpin, A. (2015-01)Purpose: To develop a perimetric test strategy, Structure Estimation of Minimum Uncertainty (SEMU), that uses structural information to drive stimulus choices. Methods: Structure Estimation of Minimum Uncertainty uses retinal nerve fiber layer (RNFL) thickness data as measured by optical coherence tomography to predict perimetric sensitivity. This prediction is used to set suprathreshold levels that then alter a prior probability distribution of the final test output. Using computer simulation, we studied SEMU’s performance under three different patient error response conditions: No Error, Typical False Positive errors, and Extremely Unreliable patients. In experiment 1, SEMU was compared with an existing suprathreshold cum thresholding combination test procedure, Estimation of Minimum Uncertainty (EMU), on single visual field locations. We used these results to finalize SEMU parameters. In experiment 2, SEMU was compared with full threshold (FT) on 163 glaucomatous visual fields. Results: On individual locations, SEMU has similar accuracy to EMU, but is, on average, one presentation faster than EMU. For the typical false-positive error condition, SEMU has significantly lower error compared with FT (SEMU average 0.33 dB lower; p < 0.001) and the 90% measured sensitivity range for SEMU is also smaller than that for FT. For unreliable patients, however, FT has lower mean and SD of error. Structure Estimation of Minimum Uncertainty makes significantly fewer presentations than FT (1.08 presentation on average fewer in a typical false-positive condition; p < 0.001). Assuming that a location in the field is marked abnormal if it falls below the 5th percentile of normal, SEMU has a false-positive rate of less than 10% for all error conditions compared with FT’s rate of 20% or more. Conclusions: On average, simulations show that using RNFL information to guide stimulus placement in a perimetric test procedure maintains accuracy, improves precision, and decreases test duration for patients with less than 15% false-positive rates.