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Crystalline materials are ubiquitous in the pharmaceutical, food, chemical and agrochemical industries, to name a few. The development of products and formulations containing crystalline solids requires the in-depth understanding and exploration of the various existing solid forms of these substances. At the same time, crystal engineering aims to design molecular crystals with directed properties, based on the knowledge of hydrogen bonding and intermolecular interactions within the crystal lattice. Such knowledge can enable delivering particles with optimized physiochemical properties, such as stability, morphology and surface chemistry, which can ultimately lead to a faster product development and more efficient formulations for specific applications. Therefore, there is a profound need of understanding how these properties related to the crystallographic characteristics of solids. In this doctoral project, different solid forms of an important food grade flavonoid substance, quercetin, including quercetin anhydrous (QA), quercetin monohydrate (QMH), quercetin dihydrate (QDH), quercetin DMSO-solvate (QDMSO), quercetin ethanol-solvate (QE) and their respective de-solvated forms, were studied in order to understand how the crystallographic structure affects the macroscopic properties of quercetin particles. The strength and nature of the intermolecular pairwise interactions (synthons) in the different structures were calculated and the lattice was comprehensively examined. The modelling work was integrated and validated with experimental solid-state characterization. It was found that crystallization of quercetin from an aqueous solvent favors the formation of hydrates, with QDH being the structure of highest stability at ambient conditions. This is because the water molecules in the lattice satisfy the hydrogen bonding interactions available in the quercetin molecules, allowing a more planar conformation of this molecule that enable the formation of stronger π-π interactions. It was, further, demonstrated that the stronger hydrogen bonding network between the quercetin and the DMSO molecules in QDMSO can lead to a higher relative thermal stability for the that structure compared to QDH, for which the hydrogen bonds between the quercetin and the water molecules were weaker. The attachment energy morphological predictions and surface chemistry analysis of quercetin forms, verified by experimental studies on the structures, demonstrated surface anisotropy and heterogeneous surface energies for the quercetin forms. The facet-specific surface chemistry was explained based on the study of the extrinsic synthons. It was shown that overall QDH has more non-polar surfaces compared to QDMSO, whose dominant surface was found to grow by polar hydrogen bonding interactions. The solid-form landscape of quercetin was also further explored, and four new structures were discovered: two new solvates (QDMSO and QE) and their de-solvated forms. The transformation conditions between the different solid forms were also established. The approach presented in this work can be extremely useful when designing products and processes involving different solid forms, specifically solvates, and for understanding and controlling the morphology and surface chemistry of crystalline solids. The interlink established between the crystal lattice and the physiochemical properties of quercetin not only elucidates the underlying chemistry behind many crystallization phenomena, such as the formation of solvates and their anisotropic nature, but also assists in enabling the prediction and design of tailor-made crystals with optimal characteristics.

The use of acoustic techniques as Process Analytical Technology (PAT) tools is relatively low compared to their electromagnetic counterparts, with buffer rod techniques having especially scarce use. Some work has been completed using acoustic techniques to monitor crystallisation and mostly consists of pulse echo techniques. Use of acoustic techniques as PAT is mostly limited to single frequency transducers and using the most basic acoustic parameters to gain information on the process. This thesis aims to fill this gap in knowledge through the use of both a buffer rod and broadband transducers for the acoustic/ultrasound monitoring of crystallisation processes. Current PAT, many of which are based on electromagnetic waves, have a range of limitations including an inability to accurately measure opaque solutions. Low powered acoustic techniques are relatively underutilised for studying phase transitions despite providing unique information - speed of sound and adiabatic compressibility of the system studied. Low power (<10 W m-2 ) pulsed acoustic techniques, such as ultrasound reflectance and velocimetry, have the benefit of being non-material altering, affordable, non-invasive and can study opaque systems without any dilution. Here we present a novel in-situ ultrasound technique, whose application is corroborated with optical turbidity in the measurement of the metastable zone width of glycine in water with good agreement. Differential scanning calorimetry (DSC) has been used extensively in a range of industries since the 1960s. However, traditional DSC is limited by small sample size and lack of stirring; additionally, it is traditionally an offline type of measurement. In particular, in the case of crystallisation, quiescent conditions present a substantial issue as nucleation times can be extremely long. Most industrial processes are on a large scale and have some degree of shear involved; therefore, the relevance of traditional DSC to industrial scale processes may be questionable. Here, the first attempt to overcome the limitations of traditional calorimetry is presented, using a novel measurement concept that applies an in-situ, non-material altering acoustic buffer rod method to measure thermal properties of aqueous solutions. This thesis aims to determine whether low-powered acoustic buffer rod techniques can be used as an effective, multipurpose PAT tool for crystallisation processes.

Cocoa butter (CB) is the foremost ingredient in chocolate, holding responsibility for the products' functional and sensorial characteristics. Numerous studies have investigated the crystallisation and polymorphism of its component triacylglycerols (TAGs), yet no correlation has been made between their stereochemistry and crystalline behaviour; even though the predominant TAG, 1-palmitoyl-2-oleoyl-3-stearoyl-glycerol (POSt), is reportedly present in a racemic mixture. Moreover, several TAGs have higher melting points than human body temperature and their behaviour in the biophysical environment of the gastrointestinal tract is yet to be reported. In this multi-faceted project, three areas of research were investigated; enantiomeric ratio elucidation of CB POSt, the effect of high melting TAGs in the digestion process and organic synthesis measures for the formulation of enantiopure POSt. For the first parameter, two approaches were assessed using a rac-POSt standard for method development, chiral HPLC and derivatisation. Both were ineffectual for enantiomeric resolution, leaving unanswered questions on the enantiomeric composition of CB. For the second parameter, an in vitro analysis procedure was used successfully in an original study on the amount of free fatty acids (FFAs) released, comparing a range of initial melt temperatures (Tm), 37, 50 and 80 oC: temperatures intended to correlate with melting points of various constituent TAGs. Similarities in total FFA release were evident, indicating high melting components had no effect on the lipolysis of CB. Finally, transesterification and chemoenzymatic procedures were undertaken for the synthesis of enantiopure POSt. Difficulties in glycerol deprotection during the latter saw a novel approach introduced in the form of a small-scale reactor (fReactor), which proved consistent in removal of the benzyl protecting group. A near identical NMR spectra of the final product with that of rac-POSt allows determination that the synthesis of (R)-POSt was a success.

Cocoa butter (CB) imparts most of the key sensory and stability characteristics in chocolate, when crystallised in the ß-V form. However, current processing methods can still be improved, since they do not account for the inherent compositional variations observed in products from different origin. Therefore, in-depth knowledge of the nanostructure of CB, and the different parameters affecting CB crystallisation is indispensable for new technologies to be developed. Two of these parameters which remain, surprisingly, under-reported are the temperature at which CB is molten prior to its crystallisation and application of medium pressure (<1000 bar). The nanostructure of the three main polymorphs of CB were determined from X-ray scattering experiments, and a novel structure in liquid CB is proposed. This is followed by the study of the effect of three thermal pre-treatments (50, 80 or 110 °C), using a multi-technique approach. Here, it was observed that by using a higher Timax, the crystallisation of the meta-stable phases was delayed, whereas the formation of the ß-V was enhanced, which is desirable for chocolate production. The differences between the 50 °C treatment and the other two treatments have been associated with the presence of crystallites of fully saturated TAG, DAG and MAG species, respectively. The effect of pressure was analysed by applying 100 to 600 bar to CB, which was subsequently cooled to 24, 26 or 28 °C, respectively. Initial post-processing analysis showed encouraging results, as crystallisation of the ß-V form appeared to be enhanced. However, these findings were not confirmed by in-situ experiments, where only the development of a-polymorphs was observed during pressurisation, which subsequently melted, to different extent, upon releasing the pressure. The observed differences might be caused by design-related issues of the pressuretreating machine used in the initial experiments.

Since its creation in 1945, the microwave has become a popular method of cooking food on both domestic and commercial scales. Despite its popularity, manufacturers have increasingly struggled to provide food products with desirable textural attributes similar to those achieved via conventional oven cooking. A prime example of this is in the potato industry where it is difficult to maintain crispy/crunchy textures of microwaved products due to moisture migration from the centre of the potato to the surface. Microwave heating primarily relies on dielectric heating with heating occurring via dipolar polarisation and ionic conduction. Previous research in this area has identified water as the main driving factor of dielectric activity due to its polar nature. In terms of this thesis, research has been conducted with the aim of understanding the science required to produce a potato chip product within the microwave oven which is able to maintain a moisture rich soft centre with a low moisture crispy exterior. The research has concluded that creation of crisp products within a microwave environment is multifactorial and strongly depends on storage time, selection of potato part and coating constituents, as well as where in the production process a coating is applied (pre fryer, post fryer or post freezer). Further investigation has also shown the importance of water and highlighted that water content alone is not an indicator of dielectric activity, but rather the ratio of free:bound water within the food product and how moisture moves throughout the product as a function of time. It has been found that addition of a polar and ion rich coating can improve product crispness of the base product although not to the same degree as deep fat frying and conventional heating. However, it must be noted that during the first 8 weeks of storage the product constantly alters in terms of moisture content, dielectric activity, acoustic activity, mechanical force measurement, recon loss and ratio of bound:free water with particular reference made to the role of moisture and sodium chloride as a ‘chemical oscillator’. This indicates that the manufacturer should not sell their product until at least 8 weeks after production if they require a high efficacy for their product. Whilst the end product produced was not as crisp as required, the research is promising with further work being required in terms of coating formulation to improve the end product crispness of potato based products within the microwave. Further work is required within the area of moisture migration due to the complex nature of the product involved.