Seed surface properties can influence crystal growth, resulting in crystals with different morphologies as well as differences in physical and bulk properties. This thesis explores the role of seed surface properties in macroscopic and microscopic pharmaceutical crystal growth, by understanding the importance of seed preparation and solvent choice based on interfacial solid-liquid and solid-vapour techniques.
Wettability studies of macroscopic fenofibrate single crystals (>1cm) was firstly undertaken, to understand how the crystal facet surfaces may influence adhesion in microscopic crystal studies. Contact angle values were found to vary from 28.7-101.9° using the water liquid probe between the different facets, depending on the conditions used for crystal growth and the facet probed. Differences were postulated to be attributed by the functional groups exposed on each facet, the densities of these functional groups, the molecular orientation of the crystal, as well as surface roughness, depending on the condition used for crystal growth. In these wettability studies, the importance of surface roughness was also highlighted using optical profilometry, where surfaces that were chemically hydrophobic, became even more hydrophobic when surface roughness was significant. This was extremely evident with crystals grown from acetonitrile for example, where crystals exhibited an average surface roughness of 8.34 µm ± 0.05 for the (-110) facet. Crystals grown from less polar solvents on the other hand, such as those grown in ethanol, exhibited a surface roughness value of 1.39 µm ± 0.54 for the (-110) facet in comparison. For such polar surfaces, such as those grown from acetonitrile for instance, larger contact angles were also noted, this was due to this additional surface roughness present on the facet surface. Resulting in lower “apparent” surface energies in comparison to crystals grown is less polar solvents, such as ethanol for example.

Using different preparations of seeds used to grow macroscopic crystals, microscopic crystal studies were then investigated to understand how the surface property of the seed and solvent choice affected crystal growth. Experiments were conducted to track the effect of seed morphology and surface energy over time, using static light scattering, scanning electron microscopy (SEM) and inverse gas chromatography (iGC) measurements. From these experiments, it was found certain conditions, such as elongated particle morphology from precipitated seeds, had a better control of crystals, with crystals grown being more homogenous in size and shape. Whereas, seeds of equant shape, such as milled seeds and silica seeds, as well plate-shaped heterogeneous seeds resulted in much larger sized crystals, with heterogeneous seeds significantly influencing agglomeration. Highlighting the importance of particle shape, size and surface free energy during crystal growth studies. The effect of surface chemistry was also highlighted, where it was observed the use of hydrophobic silanised glass could be used to control the growth of crystals for a narrow particle size distribution. The importance of solvent choice was also explored, where it was found solvents of a higher solvent polarity, such as crystals grown from acetonitrile, dispersed crystals better which also increased the particle size of crystals due to the random crystal growth, created by the wide variation in nuclei sizes growing at different rates from one another.
Therefore, it can be concluded that the surface properties of seeds, and the method of seed production are extremely important in the process, and performance of crystal growth, attributing to the final product quality of crystals.