title: Extrinsic lactose fines improve dry powder inhaler formulation performance of a cohesive batch of budesonide via agglomerate formation and consequential co-deposition.
abstract: The aim of the study was to investigate how the fine particle content of lactose carriers prepared with different types of lactose fines regulates dry powder inhaler (DPI) formulation performance of a cohesive batch of micronised budesonide. Budesonide formulations (0.8 wt%) were prepared with three different lactose carriers (Lactohale (LH) LH100, 20 wt% LH210 in LH100 and 20 wt% LH300 in LH100). Fine particle fraction of emitted dose (FPFED) and mean mass aerodynamic diameter (MMAD) of budesonide was assessed with a Next Generation Impactor (NGI) using a Cyclohaler at 90 l/min. Morphological and chemical characteristics of particles deposited on Stage 2 were determined using a Malvern Morphologi G3-ID. The results indicate that increasing concentration of lactose fines (<4.5 μm) not only increased the FPFED but also the MMAD of budesonide, suggesting drug deposition in agglomerates. Presence of agglomerates on Stage 2 was confirmed by morphological analysis of particles. Raman analysis of material collected on Stage 2 indicated that the more fine lactose particles were available the more agglomerates of budesonide and lactose were delivered to Stage 2. These results suggest drug-fines agglomerate formation is an important mechanism for how lactose fines improve and regulate DPI formulation performance.
authors.affiliation: Pharmaceutical Surface Science Research Group, Department of Pharmacy and Pharmacology, University of Bath, BA2 7AY Bath, UK. Electronic address: hanne.kinnunen@durham.ac.uk.
authors.forename: Hanne
authors.initials: H
authors.lastname: Kinnunen
authors.affiliation: DFE Pharma, Klever Strasse 187, 47574 Goch, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Hebbink
authors.affiliation: DFE Pharma, Klever Strasse 187, 47574 Goch, Germany.
authors.forename: Harry
authors.initials: H
authors.lastname: Peters
authors.affiliation: Malvern Instruments Ltd., Enigma Business Park, Grovewood Road, WR14 1XZ Malvern, UK.
authors.forename: Deborah
authors.initials: D
authors.lastname: Huck
authors.affiliation: Malvern Instruments Ltd., Enigma Business Park, Grovewood Road, WR14 1XZ Malvern, UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Makein
authors.affiliation: Pharmaceutical Surface Science Research Group, Department of Pharmacy and Pharmacology, University of Bath, BA2 7AY Bath, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Price
mesh_terms: D001993:Bronchodilator Agents / Q000737:chemistry*; D019819:Budesonide / Q000737:chemistry*; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D058995:Dry Powder Inhalers; D065347:Hypromellose Derivatives / Q000737:chemistry; D007785:Lactose / Q000737:chemistry*; D010316:Particle Size
chemical_list: D001993:Bronchodilator Agents; D002214:Capsules; D065347:Hypromellose Derivatives; D019819:Budesonide; D007785:Lactose
keywords: Dry powder inhaler; Lactose; Raman spectroscopy