Formulation and protein stabilisation

There are several possible ways in which the physical stability of the protein can be improved through formulation. We will examine methods for minimising this and chemical degradation in the following sections. 

Some measures can be taken to eliminate, or at least minimise, protein denaturation resulting 

Some excipients and buffer components added to the protein solution are able to minimise denaturation through their effects on 

Cosolvent effects such as this can be analysed from a thermodynamic point of view. Addition of cosolvents which cause preferential hydration of the protein stabilises the compact conformations of the protein because the cosolvent results in an increase in the free energy of the system. To reduce the free energy, the surface area of the protein is minimised. 

In order to avoid stability problems arising from charge neutralisation and to ensure adequate solubility, a pH must be selected which is at least 0.5 pH units above or below the isoelectric point. This is often difficult to achieve, however, since a pH range of 5-7 is usually required to minimise chemical breakdown and this frequently coincides with the isoelectric point. 

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