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Title: Prediction of the mechanical properties of molecular crystals based upon their crystallographic structure
Author: Ibrahim, Siti Fatimah Binti
ISNI:       0000 0004 5922 122X
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2016
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The APIs mechanical properties particularly, tabletability and flowability are of significant interest in the drug dosage tabletting. Insights into the APIs mechanical behaviour not only assist in the selection of optimum tabletting process but the choice of suitable excipients for dosage blend. Prediction of the mechanical properties of seven solid forms was described in this study two of which were used at the initial stage to develop the model. The objective of the model is to test the reliability of applying molecular and crystallographic modelling to predict the slip behaviour of APIs which will provide a quick tool for observing the mechanical properties. Plane rugosity and interlock properties were calculated for the first time by taking the crystallographic properties of each compound. The prediction model comprises of three main components. Firstly, the identification of likely dislocation Burgers vectors based on lattice geometry and dependency to line dislocation; secondly, selection of slip planes for plastic deformation using the calculation of interplanar interactions, rugosity and surface energy and thirdly, characterisations of slip systems or propensity for cleavage and fracture. The pentaerythritol and its derivative, pentaerythritol tetranitrate were selected as the basis structure during development of model because of known cleave and plastic behaviour. From the calculation, the primary Burgers vector for pentaerythritol was identified as ½ [111], and the prominent slip plane for pentaerythritol is a non-habit plane of (001). The (001) was 94% behaving as an ideal slip plane. However, the primary slip system of pentaerythritol was inactive because the Burgers vector was not in the (001) plane. Pentaerythritol was predicted to cleave at (001) because of strong intraplanar intermolecular interactions. In contrast, pentaerythritol tetranitrate was predicted to undergo deformation by slipped on the plane (110) and in the direction of [001]. The (110) was behaving with 82% of ideal slip plane. The predicted slip behaviour was agreeing with the micro-indentation measurements in the literature. Five solid forms of paracetamol, namely polymorph I and II, paracetamol theophylline, paracetamol trihydrates and paracetamol hydrochloride monohydrate were tested using the developed model to verify the prediction robustness. The influence of each component towards the mechanical behaviour of paracetamol varies depending on intermolecular interactions present in the crystal system.
Supervisor: Roberts, Kevin ; Ramachandran, Vasuki ; Docherty, Robert Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available