title: In vitro dry powder inhaler formulation performance considerations.
abstract: It has long been desired to match airflow conditions during formulation evaluation to those of relevance to lung deposition. In this context several strategies have been adopted involving sampling at different: flow rate (without consideration of flow conditions, e.g. shear, Reynolds number, work function); pressure drop (with and without consideration of flow conditions) and; flow rate and pressure drop. Performance testing has focused on the influence of these sampling conditions on delivered dose uniformity and aerodynamic particle size distribution. However, in order to be physiologically relevant it is also important to know when the drug was delivered with respect to initiation of airflow as variation in this parameter would influence lung deposition. A light obscuration method of detecting the dose delivered from a dry powder inhaler while sampling for aerodynamic particle size distributions (APSD) by inertial impaction has been developed. Four formulations of albuterol sulfate and budesonide in sieved and milled lactose, respectively, were dispersed and their rate of delivery monitored. The differences observed have the potential to impact the site of delivery in the lungs. The rate of delivery of drug is clearly an important companion measurement to delivered dose and APSD if the intent is to predict the similarity of in vivo performance of dry powder inhaler products.
authors.affiliation: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 25599-7571, USA; F. Hoffman-La Roche Ltd, Basel, Switzerland.
authors.forename: Susanne
authors.initials: S
authors.lastname: Ziffels
authors.affiliation: RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709, USA.
authors.forename: Norman L
authors.initials: NL
authors.lastname: Bemelmans
authors.affiliation: RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709, USA.
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Durham
authors.affiliation: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 25599-7571, USA; RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Hickey
mesh_terms: D000420:Albuterol / Q000008:administration & dosage / Q000493:pharmacokinetics; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D019819:Budesonide / Q000008:administration & dosage / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D058995:Dry Powder Inhalers; D005079:Excipients; D066298:In Vitro Techniques; D007785:Lactose; D010316:Particle Size; D011208:Powders
chemical_list: D018927:Anti-Asthmatic Agents; D004337:Drug Carriers; D005079:Excipients; D011208:Powders; D019819:Budesonide; D007785:Lactose; D000420:Albuterol
keywords: Aerodynamic particle size distribution; Aerosols; Deliver dose; Delivery rate; Flow rate; In vitro testing; Inhalation; Lungs; Pressure drop