ABSTRACT
INTRODUCTION There are numerous unique, critical applications for proteins in human healthcare (1-3). However, even the most promising and effective protein therapeutic will not be of benefit if its stability cannot be maintained during packaging, shipping, long-term storage, and administration. For ease of preparation and cost containment by the manufacturer and ease of handling by the end user, an aqueous protein solution often is the preferred formulation. However, proteins are readily denatured (often irreversibly) by the numerous stresses arising in solution, for example, heating, agitation, freezing, pH changes, and exposure to interfaces or denaturants (4). The result is usually inactive protein molecules and aggregates, which compromise clinical efficacy and increase the risk of adverse side effects (5). Even if its physical stability is maintained, a protein can be degraded by chemical reactions (e.g., hydrolysis and deamidation), many of which are mediated by water. Thus, inherent protein instability and/or the logistics of product handling often precludes development of aqueous, liquid formulations (6,7). Also, simply preparing stable frozen products, which is relatively straightforward, is not a practical alternative because the requisite shipping and storage conditions are not technically and/or economically feasible in many markets.
