Interactions between therapeutic protein formulations and surfaces

Abstract

Therapeutic protein formulations encounter a multitude of different surfaces in every part of their production, packaging, storage and administration to patients. These interfaces can be very different---chemically---from the formulation's solution chemistry and can have unintended, negative effects on the formulation. Protein molecules can adsorb to these surfaces, which can induce structural perturbations in the therapeutic and promote aggregation. Components from the formulation can be absorbed into the surfaces, altering the formulation solution conditions, which can bring about additional stresses on the therapeutic. Formulations can even chemically modify surfaces they come in contact with, altering the surface properties. Understanding such interactions between formulations components and surfaces is critical to developing better storage and delivery devices and improved formulations. In this work, I examined the pharmaceutical compatibility of a novel syringe plunger coating---designed to be used in silicone oil-free, pre-filled syringes---and found it to cause much less protein aggregation during agitation than was observed in a traditional siliconized syringe. Second, I found that plastics found in catheters absorbed phenolic compounds from insulin analog formulations and that this depletion had a profound impact on different insulin analogs' assembly states and stabilities under thermal stress. Finally, I also found that zinc ions, found in insulin formulations as well, chemically damaged analytical size exclusion chromatography columns, which are used to monitor soluble aggregates of insulin in therapeutic formulations.