Biological dosage forms: the application of crystal engineering

This thesis describes the novel multicomponent crystals obtained through a cocrystallisation screening with L-Leucine peptides synthesised through Solid Phase Peptide Synthesis. The aim of the project was to investigate the ability of short hydrophobic peptides to generate crystalline systems with a wide range of coformers, and to study the intermolecular interactions involved in such structures. In this sense, the Cambridge Structural Database and literature show a lack of systematic studies. Moreover, the peptides used for this project did not undergo the typical purification stage to remove the trifluoroacetate (TFA) contamination deriving from the cleavage steps. This process is routinely performed through chromatography and ion exchange reaction, inevitably leading to consistent loss in peptide yields. For the first time, crystal engineering concepts have been used as a proof of concept for an alternative method of purification, exploiting the differential crystallisation pathways established during the crystallisation. The structures described in the present work are part of a wide landscape of outcomes with different composition and framework features. Both TFA-free and TFA-contaminated multicomponent crystals are herein analysed and described, in a first attempt to study the impact of the contaminating agent on the crystallisation process of non-purified freshly synthesised peptide. Several unexpected crystallisation products are included to show the complexity and unpredictable behaviour of the various species involved in the cocrystallisation process