Hydroxypropyl-beta-cyclodextrin inhibits spray-drying-induced inactivation of beta-galactosidase.

The single-step, fast spray-drying process may represent a valuable alternative to the multistep, time-consuming freeze-drying process in the area of formulation and processing of biopharmaceuticals. In this study, we tested the use of sucrose and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as stabilizing excipients in the spray-drying of a model protein, beta-galactosidase. The solutions were processed using a Büchi 190 cocurrent Mini Spray Dryer at an outlet temperature of 61 +/- 2 degrees C. The powders were redissolved and analyzed for catalytic activity, aggregation, chemical decomposition, and thermal susceptibility as observed by high-resolution calorimetry. Spray-drying significantly inactivated beta-galactosidase. Spray-drying beta-galactosidase in the presence of sucrose did not prevent inactivation. However, after spray-drying beta-galactosidase in the presence of HP-beta-CD, or HP-beta-CD and sucrose, full catalytic activity was exhibited on reconstitution. Furthermore, the reconstituted product was unchanged in terms of molecular weight, charge, and thermal stability. These findings are consistent with a hypothesis that the change responsible for inactivation of beta-galactosidase was mainly a monomolecular, noncovalent change, i. e., the formation of incorrect structures, that arose from surface denaturation. This study clearly demonstrates that cyclodextrins can be useful stabilizing excipients in the preparation of spray-dried protein pharmaceuticals.