Stabilization Effects of Saccharides in Protein Formulations: a Review of Sucrose, Trehalose, Cyclodextrins and Dextrans

Eur J Pharm Sci. 2023 Oct 31:106625. doi: 10.1016/j.ejps.2023.106625. Online ahead of print.ABSTRACTSaccharides are a popular group of stabilizers in liquid, frozen and freeze dried protein formulations. The current work reviewed the stabilization mechanisms of three groups of saccharides: (i) Disaccharides, specifically sucrose and trehalose; (ii) cyclodextrins (CDs), a class of cyclic oligosaccharides; and (iii) dextrans, a class of polysaccharides. Compared to sucrose, trehalose exhibits a more pronounced preferential exclusion effect in liquid protein formulations, due to its stronger interaction with water molecules. However, trehalose obtains higher phase separation and crystallization propensity in frozen solutions, resulting in the loss of its stabilization function. In lyophilized formulations, sucrose has a higher crystallization propensity. Besides, its glass matrix is less homogeneous than that of trehalose, thus undermining its lyoprotectant function. Nevertheless, the hygroscopic nature of trehalose may result in high water absorption upon storage. Among all the CDs, the β form is believed to have stronger interaction with proteins than the α- and γ-CDs. However, the stabilization effect, brought about by CD-protein interactions, is case-by-case - in some examples, such interactions can promote protein destabilization. The stabilization effect of hydroxypropyl-β-cyclodextrin (HPβCD) has been extensively studied. Due to its amphiphilic nature, it can act as ...
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Source Type: research