title: Hydroxypropyl-beta-cyclodextrin inhibits spray-drying-induced inactivation of beta-galactosidase.
abstract: 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.
authors.affiliation: Drug Delivery Group, The School of Pharmacy, University of Bradford, Bradford, BD7 1DP, UK.
authors.forename: S
authors.initials: S
authors.lastname: Branchu
authors.forename: R T
authors.initials: RT
authors.lastname: Forbes
authors.forename: P
authors.initials: P
authors.lastname: York
authors.forename: S
authors.initials: S
authors.lastname: Petrén
authors.forename: H
authors.initials: H
authors.lastname: Nyqvist
authors.forename: O
authors.initials: O
authors.lastname: Camber
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002152:Calorimetry, Differential Scanning; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000494:pharmacology*; D003890:Desiccation; D004355:Drug Stability; D004591:Electrophoresis, Polyacrylamide Gel; D006358:Hot Temperature; D007525:Isoelectric Focusing; D011489:Protein Denaturation; D047392:beta-Cyclodextrins; D001616:beta-Galactosidase / Q000737:chemistry*
chemical_list: D003505:Cyclodextrins; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D001616:beta-Galactosidase