Instability, stabilization, and formulation of liquid protein pharmaceuticals; A Review
Abstract
Protein-based pharmaceuticals have become indispensable in modern medicine because of their high specificity and therapeutic efficacy. However, unlike conventional small-molecule drugs, proteins are inherently unstable and susceptible to both physical and chemical degradation during manufacturing, storage, and administration. This review discusses the mechanisms responsible for protein instability, including denaturation, unfolding, aggregation, oxidation, deamidation, hydrolysis, and disulfide bond rearrangement. It further explains the fundamental principles governing protein folding, conformational stability, and the influence of environmental factors such as temperature, pH, ionic strength, mechanical stress, and formulation components. The article also highlights various stabilization strategies including optimization of formulation conditions, use of stabilizing excipients, control of processing conditions, and appropriate storage methods. Analytical techniques for monitoring protein stability are reviewed to ensure product quality and therapeutic efficacy. Overall, the review provides a comprehensive understanding of protein behavior and formulation approaches that support the successful development of stable liquid protein pharmaceuticals.
