title: Stabilisation of proteins via mixtures of amino acids during spray drying.
abstract: Biologicals are often formulated as solids in an effort to preserve stability which generally requires stabilising excipients for proper drying. The purpose of this study was to screen amino acids and their combinations for their stabilising effect on proteins during spray drying. Catalase, as model protein, was spray dried in 1+1 or 1+2 ratios with amino acids. Some amino acids namely arginine, glycine and histidine showed good retention of catalase functionality after spray drying and subsequent storage stress. A 1+1 combination of arginine and glycine in a 1+2 ratio with catalase resulted in a tremendously good stabilising effect. Storage at high temperature/humidity also showed beneficial effects of this combination. To evaluate whether this was a general principle, these findings were transferred to an antigenic protein of comparable size and supramolecular structure (haemagglutinin) as well as to a smaller enzyme (lysozyme). Upon spray drying with the combination of amino acids it could be shown that both proteins remain more stable especially after storage compared to the unprotected protein. The combination of arginine and glycine is tailored to the needs of protein stabilisation during spray drying and may hence be utilised in dry powder formulation of biomolecules with superior stability characteristics.
authors.affiliation: Kiel University, Department of Pharmaceutics and Biopharmaceutics, Grasweg 9a, D-24118 Kiel, Germany.
authors.forename: Ankur
authors.initials: A
authors.lastname: Ajmera
authors.affiliation: Kiel University, Department of Pharmaceutics and Biopharmaceutics, Grasweg 9a, D-24118 Kiel, Germany. Electronic address: rscherliess@pharmazie.uni-kiel.de.
authors.forename: Regina
authors.initials: R
authors.lastname: Scherließ
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000956:Antigens, Viral / Q000737:chemistry; D002374:Catalase / Q000737:chemistry* / Q000378:metabolism; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000378:metabolism; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism; D011208:Powders
chemical_list: D000596:Amino Acids; D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011208:Powders; D002374:Catalase; D009113:Muramidase
keywords: Amorphous matrix; Catalase; Haemagglutinin; Lysozyme; Thermal stability; Water replacement