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Title: Co-crystallisation of active pharmaceutical ingredients
Author: Srirambhatla, Vijay Kumar
ISNI:       0000 0004 8503 5615
Awarding Body: Heriot-Watt University
Current Institution: Heriot-Watt University
Date of Award: 2014
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In the thesis presented here, novel co-crystals of two active pharmaceutical ingredients (APIs), i.e. paracetamol and furosemide are presented. Co-crystals are molecular complexes in which two or more components are held together through non-covalent interactions. The work on co-crystals was aimed to investigate and identify robust hydrogen bonds and primary structural motifs which can be used to predict the solid-state assembly in related molecular complexes. The Database mining based on retro-synthetic approach followed by co-crystal screening using mechano-chemical and crystallisation methods in conjunction with high-throughput powder X-ray analysis led to the discovery of four novel co-crystal forms of paracetamol. The study shows that a balance between the retrosynthetic approach and database screening of supramolecular synthons provides a useful approach for targeted co-crystal synthesis. The ability of charge transfer hydrogen bonding interaction to drive the assembly of molecules in co-crystals was investigated. This led to the synthesis of a series of isostructural host-guest complexes of furosemide. It has been discovered that charge transfer interaction drives the crystal packing arrangement in presence of other hydrogen bonding interactions. The ability of two component physical mixture to form ternary co-crystals has been investigated. Systematic synthesis with careful selection of components based on simple geometric principles led to the discovery of a series of ternary co-crystals stabilised through a novel two-dimensional hydrogen-bonded network, which serves a prototype for a new family of ternary co-crystals. This has enabled a targeted approach for the selection and synthesis of new ternary co-crystals with control over symmetry and gross structural features. The study demonstrates that networks that maintain their dimensionality and integrity provide a degree of predictability in the crystal packing arrangements in the solid state.
Supervisor: Powell, Anthony Vivian ; Kraft, Arno Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available