engleski

Protein instability and stability, a formulation challenge

Development of stable protein or peptide formulation is one of the critical steps in pharmaceutical protein formulation development, towards to the final therapeutic product. A major challenge is to maintain the integrity of a protein drug during pharmaceutical processing, storage, handling and administration, knowing that proteins typically raise more stability issues than “small molecules” as a result of macromolecular instability and complexity (numerous reactive chemical centers and degradable elements). Stability issues start with preservation of delicate 3-D structure stabilized by noncovalent interactions such as hydrogen bonding, ionic interactions, Van der Waals’ forces and hydrophobic packing and end with protection of linear amino acid sequence and potential post-translational modifications. By determining stabilizing effect of a given stabilizer under the specific physico-chemical conditions, selection and/or comparison of the stabilizers used followed by statistical evaluation bring out general rules that can be applied to prevent unwanted protein/peptide degradation processes. As the science of formulating protein drug today is very much an interdisciplinary problem, together with new advances in the fields such as medicinal research, analytical and pharmaceutical development, manufacturing (process chemistry and engineering), as well as quality and regulatory requirements, new topics in the area of protein formulation emerge.

Protein; Instability; Stability; Pharmaceutical formulation

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