Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.777652
Title: Physicochemical and computational approaches for the prediction of the manufacturability of active pharmaceutical ingredients
Author: Hooper, Debbie
ISNI:       0000 0004 7963 4275
Awarding Body: University of Greenwich
Current Institution: University of Greenwich
Date of Award: 2018
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Abstract:
Tablets have aided the delivery of active pharmaceutical ingredients (APIs) to patients since the 1800s, however tablet failure, such as punch sticking and tablet hardness issues, during manufacturing is still common. The techniques currently available for the prediction of manufacturability of tablets are not adequately representative of bulk solid properties. There is, therefore, a need to develop new and appropriate characterisation techniques for use in pharmaceutical material evaluation. This is particularly important to ensure that at the manufacturing stage the material properties of medicines are fully understood and predictable to enable optimum manufacturing performance. This thesis presents a novel approach of experimentally predicting punch sticking and deformation properties of APIs. Four diverse particle shapes of ibuprofen, with similar physicochemical properties are reported herein and a correlation between particle shape and sticking propensity established. Ibuprofen particles with a regular particle shape exhibit a greater tendency to stick compared to particles with a needle like particle shape. Surface energy analysis, both experimentally and computationally, reveals that particles with a more regular shape contain a larger proportion of crystal faces that exhibit a higher surface energy driven by the specific energy component. This provides a link between ibuprofen sticking propensity and surface energy. The sticking propensity and surface energy of two further APIs, palbociclib and crizotinib, are reported. In general, particles with regular shapes exhibit higher surface energies and a greater propensity to stick. The specific surface energy measured experimentally and total surface energy measured computationally have been shown as useful tools to fundamentally understand the surface chemistry. These attributes can be used to explain different sticking behaviour between different shapes of the same API, where particles with a high proportion of crystal faces containing unsaturated high energy intermolecular interactions at the surface are more likely to stick. This fundamental understanding could be used to engineer API particle shapes through crystallisation to ultimately reduce punch sticking and minimise production issues during tableting processes.
Supervisor: Mitchell, John ; Snowden, Martin ; Clarke, Fiona Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.777652  DOI: Not available
Keywords: QD Chemistry
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