CHAMBERS, LUKE,IAN (2022) Multicomponent Solid Forms in Pharma, Hair Care and Dental Care. Doctoral thesis, Durham University.
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This work covers multicomponent solid forms including co-amorphous solid forms with active pharmaceutical ingredients (APIs) and, co-crystals, salts, hydrates and solvates to help model intermolecular interaction taking place in larger systems including polymers and proteins. A new prediction model was created to help identify which combinations of APIs and small molecule co-formers were likely to form co-amorphous systems. The prediction model suggests co-amorphous formation is related to the average molecular weight of the two components and the strength of the intermolecular interactions formed. A new co-amorphous screen containing mebendazole with 29 co-formers was performed and compared to the predicted results, which showed a predictive hit rate of 90%.
The dimer of vinylcaprolactam (bisVCap) was used in a co-amorphous screen with 13 APIs. The experimental results were compared to the predicted results with 11 out of 13 systems correctly predicted. The co-amorphous systems found were analysed by FTIR which identified new intermolecular interactions formed between bisVCap and the APIs, stabilising the co-amorphous state.
Crystals of a hydrogenated dimer of vinylpyrrolidone and hydrogen peroxide were grown by cooling crystallisation and characterised by SXRD. The structures were used to identify the bonding models present in a polyvinylpyrrolidone hydrogen peroxide complex. The crystal structures were combined with DFT calculations to produce two new proposed structures of the hydrogen bonding in the polyvinylpyrrolidone hydrogen peroxide complex.
A hair care mixture formed from a gluconamide and a gluconate and 3-hydroxypropyl ammonium salt, is known to strengthen hair fibres; however, the process is unknown. To identify potential interactions between the mixture and hair fibres, a range of crystals were grown. The crystals were identified by SXRD as two polymorphic forms of the gluconamide and three salts of 3-hydroxypropylammonium with sulfuric acid, methane sulfonic acid and oxalic acid. The new crystal structures and structures from the Cambridge structural database were used to speculate potential interactions formed. The gluconamide was identified to be a supramolecular gelator in aniline and benzyl alcohol. The gels were characterised by rheology, scanning electron microscopy, 1H NMR, FTIR and XRPD.
|Item Type:||Thesis (Doctoral)|
|Award:||Doctor of Philosophy|
|Keywords:||Crystallisation, Co-crystals, salts, co-amorphous, hydrogen peroxide, API|
|Faculty and Department:||Faculty of Science > Chemistry, Department of|
|Copyright:||Copyright of this thesis is held by the author|
|Deposited On:||14 Mar 2022 08:56|