ABSTRACT

As discussed in Chapter 3, peptides and proteins undergo adsorption to air-water and solid-water interfaces. Such interfaces are readily generated during processing. For example, mixing of solutions will generate extensive air-water interfaces because of the resulting turbulence, and filtration of solutions will generate a solid-water interface. Even after the final product is marketed, the container headspace still provides an air-water interface, and the container walls provide a solid-water interface. Important determinants of adsorption on a solid-water interface will be surface-to-volume ratio, chemical nature of the solid, and the solution/ionic properties of the protein in the formulation. The adsorption may be minimized by reducing the surface area or solid exposed to solution, selecting a surface with minimum adsorption, or controlling the solution properties of the protein. The solution properties of the protein can be controlled by changing the pH or ionic strength or by addition of cosolvents. For adsorption on air-water interfaces, shaking must be minimized. The other approach to prevent adsorption, obviously, is the addition of appropriate pharmaceutical excipients to the formulation.