title: Nano- and Microstructured model carrier surfaces to alter dry powder inhaler performance.
abstract: The present study investigates the effect of different carrier surface modifications on the aerosolisation performance and on the effective carrier payload of interactive blends for inhalation. Two different active pharmaceutical ingredients (APIs) were used: Formoterol fumarate dihydrate (FF) and budesonide (BUD). Blends were prepared with glass beads as model carriers which have been subjected to mechanical surface modifications in order to introduce surface roughness via treatment with hydrofluoric acid (HF) and/or milling with tungsten carbide (TC). As far as effective carrier payload, in this study expressed as true surface coverage (TSC), is concerned, surface modification had varying effects on blends containing BUD or FF. Aerodynamic characterisation in vitro showed a significant decrease in respirable fraction for glass beads treated with HF (40.2-50.1%), due to the presence of clefts and cavities, where drug particles were sheltered during inhalation. In contrast, grinding with TC leads to surface roughness on a nano scale, ultimately increasing aerodynamic performance up to 20.0-38.1%. These findings are true for both APIs, regardless of their chemical properties.
authors.affiliation: Department of Pharmaceutics and Biopharmaceutics, Kiel University, Grasweg 9a, 24118 Kiel, Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Renner
authors.affiliation: Deva Holding A.S., Istanbul, Turkey.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Steckel
authors.affiliation: Daiichi-Sankyo, Pfaffenhofen, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Urbanetz
authors.affiliation: Department of Pharmaceutics and Biopharmaceutics, Kiel University, Grasweg 9a, 24118 Kiel, Germany. Electronic address: rscherliess@pharmazie.uni-kiel.de.
authors.forename: Regina
authors.initials: R
authors.lastname: Scherließ
mesh_terms: D000336:Aerosols; D001993:Bronchodilator Agents / Q000737:chemistry; D019819:Budesonide / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D058995:Dry Powder Inhalers; D000068759:Formoterol Fumarate / Q000737:chemistry; D005898:Glass / Q000737:chemistry*; D006858:Hydrofluoric Acid / Q000737:chemistry; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D013499:Surface Properties; D017973:Tungsten Compounds / Q000737:chemistry
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D004337:Drug Carriers; D017973:Tungsten Compounds; C002802:tungsten carbide; D019819:Budesonide; D006858:Hydrofluoric Acid; D000068759:Formoterol Fumarate
keywords: Budesonide (PubChem CID: 5281004); Dry powder inhaler; Formoterol fumarate (PubChem CID: 53477580); Glass beads; Impaction analysis; Roughness; Surface modification