title: The Production of a Stable Infliximab Powder: The Evaluation of Spray and Freeze-Drying for Production.
abstract: In prospect of developing an oral dosage form of Infliximab, for treatment of Crohn's disease and rheumatoid arthritis, freeze-drying (vial vs Lyoguard trays) and spray-drying were investigated as production method for stable powders. Dextran and inulin were used in combination with sucrose as stabilizing excipients. The drying processes did not affect Infliximab in these formulations, i.e. both the physical integrity and biological activity (TNF binding) were retained. Accelerated stability studies (1 month at 60°C) showed that the TNF binding ability of Infliximab was conserved in the freeze-dried formulations, whereas the liquid counterpart lost all TNF binding. After thermal treatment, the dried formulations showed some chemical modification of the IgG in the dextran-sucrose formulation, probably due to Maillard reaction products. This study indicates that, with the appropriate formulation, both spray-drying and freeze-drying may be useful for (bulk) powder production of Infliximab.
authors.affiliation: Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands.|University of Groningen, Department of Pharmaceutical Technology and Biopharmacy, Groningen, The Netherlands.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Kanojia
authors.affiliation: Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands.
authors.forename: Rimko Ten
authors.initials: RT
authors.lastname: Have
authors.affiliation: AIMM Therapeutics, Amsterdam, The Netherlands.
authors.forename: Arjen
authors.initials: A
authors.lastname: Bakker
authors.affiliation: AIMM Therapeutics, Amsterdam, The Netherlands.
authors.forename: Koen
authors.initials: K
authors.lastname: Wagner
authors.affiliation: University of Groningen, Department of Pharmaceutical Technology and Biopharmacy, Groningen, The Netherlands.
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
authors.affiliation: Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands.|Leiden Academic Centre of Drug Research, Drug Delivery Technology, Leiden, The Netherlands.
authors.forename: Gideon F A
authors.initials: GF
authors.lastname: Kersten
authors.affiliation: Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Amorij
mesh_terms: D002850:Chromatography, Gel; D003911:Dextrans / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D004591:Electrophoresis, Polyacrylamide Gel; D005612:Freeze Drying; D000069285:Infliximab / Q000032:analysis / Q000737:chemistry*; D007444:Inulin / Q000737:chemistry; D015416:Maillard Reaction; D013395:Sucrose / Q000737:chemistry
chemical_list: D003911:Dextrans; D013395:Sucrose; D007444:Inulin; D000069285:Infliximab