Hydroxypropyl-beta-cyclodextrin inhibits spray-drying-induced inactivationof beta-galactosidase

The single-step, fast spray-drying process may represent a valuable alterna tive 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-cyclodexlrin (HP-beta-GD) as stab ilizing excipients in the spray-drying of a model protein, beta-galactosida se. The solutions were processed using a Buchi 190 cocurrent Mini Spray Dry er at an outlet temperature of 61 +/- 2 degrees C. The powders were redisso lved and analyzed for catalytic activity, aggregation, chemical decompositi on, and thermal susceptibility as observed by high-resolution calorimetry. Spray-drying significantly inactivated beta-galactosidase. Spray-drying bet a-galactosidase in the presence of sucrose did not prevent inactivation. Ho wever, after spray-drying beta-galactosidase in the presence of HP-beta-CD, or HP-beta-CD and sucrose, full catalytic activity was exhibited on recons titution. Furthermore, the reconstituted product was unchanged in terms of molecular weight, charge, and thermal stability. These findings are consist ent with a hypothesis that the change responsible for inactivation of beta- galactosidase was mainly a monomolecular, noncovalent change, i.e., the for mation of incorrect structures, that arose from surface denaturation. This study clearly demonstrates that cyclodextrins can be useful stabilizing exc ipients in the preparation of spray-dried protein pharmaceuticals.