One of the significant aspects of the production of proteins is the discussion of their stability and solubility. Studying the stability of proteins and identifying factors that increase their stability, is one of the important and interesting topics in scientific societies. The production of biotech medicinal proteins plays an important role in the fight against diseases. Proteins are stable only in a limited range of temperature and acidity conditions and are very susceptible to physical and chemical degradation. Today, various solutions have been proposed to increase the solubility and stability of proteins, which include guided changes in the protein molecule and optimization in the instructions for expression, purification, and the solubility process of proteins, which most of the time, the first approach is not possible and achievable. This review study provides solutions to increase the stability of proteins at different levels, including investigating the impact of the design of the expression structure, sequence, and protein sequences on stability, the optimal selection of the host cell, and the improvement of the expression conditions be also discussed. In addition, the effect of optimization of buffers used in pharmaceutical formulations, such as the selection of suitable amino acids and osmolytes to increase protein stability, and the effect of sugars and polyols on the stability of recombinant pharmaceutical proteins are also investigated.
