Walking on thin ice: controlled freezing & thawing of pharmaceutical active molecules

Abstract

Cryopreservation of active pharmaceutical ingredients, cells, or tissues is fundamental to maintain the quality of the respective product. Ice formation, re-crystallization, and other phenomena that occur during the freezing and thawing process can cause significant damage. These ice-induced injuries can be minimized by appropriate molecule design and the use of chemical cryoprotectants or bio-substances in combination with suitable equipment and physical conditions during the freezing and thawing process. It is important to adapt both freezing and thawing processes to the characteristics of the protein or active pharmaceutical ingredient that requires a cold chain to maintain its biological and chemical stability during storage and shipment. Controlled freezing and thawing facilitates consistent product quality during the fluid management processes involved in manufacturing. By preventing damage to active ingredients, the supply of medications is optimized.

Current opinion: advances in machine perfusion and preservation of vascularized composite allografts – will time still matter?

“…However, freezing the intracellular and extracellular water is the main danger of this approach, as resulting ice crystals cause mechanical injury to the cellular structure and osmotic stress. Fortunately, cryoprotective agents (CPAs), which were first introduced in 1949, mitigate this issue by largely controlling ice formation, but do not altogether eliminate its existence [24]. While commonly used CPAs like dimethyl sulfoxide (DMSO), ethylene glycol, glycerol, sorbitol, 2,3butanediol and 1,4-butanediol have successfully preserved single-cell suspensions, the transition to VCAs generally falls short [25][26][27][28][29].…”