Solid-state protein formulations
Protein-based medicines are essential, but their stability remains a major challenge. This thesis investigates how excipients, such as sugars and amino acids, form a protective ‘glass matrix’ during freeze-drying by replacing water molecules and restricting movement at the molecular level.The studies focused on unraveling these mechanisms. Research was conducted into how combinations of the amino acid arginine and the sugar molecule pullulan affect the stability of specific model proteins under varying temperatures and humidity levels.
To make this process less dependent on trial-and-error, a computer model was employed to simulate how protective molecules arrange themselves around a protein. These simulations were used to test whether the degree to which the protein surface is ‘covered’ can predict the minimum amount of excipient required in practice.Additionally, an accelerated testing method was developed to freeze dry and screen a broad range of excipient combinations simultaneously using minimal amounts of material.
Furthermore, the research explored how this ‘toolbox’ of excipients could be applied more broadly, for instance, in the development of inhalable powders. Experiments were also conducted with 3D-printing tablets at room temperature. This involved attempting to stabilize proteins within a sugar matrix and providing them with a protective coating for targeted release in the intestines.