Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610963
Title: Exploring the role of the amorphous state in pharmaceutical co-crystal production
Author: Majumder, Mridul
Awarding Body: University of Reading
Current Institution: University of Reading
Date of Award: 2013
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Abstract:
Pharmaceutical co-crystals are multicomponent crystalline materials with defined stoichiometry, often stabilized by hydrogen bonding. Numerous studies into co-crystals have been carried out over the last decade or so with the primary aim being to improve the bioavailability of poorly soluble drugs by this crystal engineering technique. However, knowledge gaps remain in understanding the mechanisms by which co-crystals are formed in the solid-state, screening strategies and scale up processes leading to formulation development that are key to success using this approach. The research presented herein mainly focuses upon mechanisms by which pharmaceutical co-crystals are produced in the solid-state. In addition, to protect intellectual property of a drug molecule, co-crystal diversity in terms of polymorphic forms, hydrates/solvates, salt/co-crystals formation, polymorphic co-crystals/salts formation are considered. Hence, an approach towards producing polymorphic co-crystals using different polymorphic forms of an API was studied. Neat grinding and milling were used extensively throughout this work and a novel co-crystal was made which was also found to be polymorphic and distinct from forms manufactured via the liquid state. Methodology solving crystal structures from powder X-ray diffraction data was successfully employed for two co-crystal models. An H-bond propensity calculation was carried out and it is hypothesized that this informatics-based evidence will aid selection of likely co-formers for co-crystals along with an alternative favourable H-bonding scheme for a novel polymorphic co-crystals. Finally, the role of amorphous states in the formation of co-crystals by grinding was found to be a key factor along with energetically and highly kinetically driven situations. The co-crystals formation in the solid-state is a "thermodynamically driven kinetic process" with an apparent "activation energy" needed to be overcome to initiate the process.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.610963  DOI: Not available
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