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Title: Probing pharmaceutical materials using atomic force microscopy
Author: Cassidy, A. M. C.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2010
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Microscopic techniques were used to study the surface behaviour of model active pharmaceutical ingredients (APIs) and excipients, while under stress, and this was compared with the response of the bulk material. The model APIs were caffeine/oxalic acid, caffeine/malonic acid cocrystals and aspirin whilst spheronised microcrystalline cellulose (s-MCC), pregelatinised starch (PGS) and dicalcium phosphate dehydrate served as examples of excipients. The difference between the surface and bulk behaviour of caffeine cocrystals in response to storage in controlled humidity environments was investigated. Surface imaging illustrated an anisotropic element to the microstructure of the caffeine cocrystals, which became more pronounced at the extremities of relative humidity (RH) storage. The trends in surface reactivity which were observed for the cocrystals were found to follow those previously reported for bulk behaviour, using PXRD. Atomic force microscopy imaging, however, gave an earlier indication of incompatibility between the ecocrystals and > 75% RH, with surface transformations occurring on a shorter timescale than indicated from the results of bulk analysis. This work represents the first reported analysis of organic molecular cocrystals by AFM. The material properties and subsurface structure of s-MCC and PGS were examined using AFM. Phase imaging and force measurements identified heterogeneity in the material properties of these excipient particles. In the case of s-MCC, the results were used to support a theory for intragranular porosity. The solid-state hydrolysis of aspirin crystals in the presence of dicalcium phosphate dehydrate was studied, using in situ AFM techniques.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available