title: Interaction of Formulation and Device Factors Determine the In Vitro Performance of Salbutamol Sulphate Dry Powders for Inhalation.
abstract: A variety of capsule-based dry powder inhalers were used to evaluate formulation-device interaction. The in vitro deposition of salbutamol sulphate (SS) was compared directly to published data for salmeterol xinafoate (SX). A 3(2) factorial design was used to assess the effect of SS formulations with three blends of different grade coarse lactose supplemented with different levels of fine lactose. These formulations were tested for homogeneity and evaluated for their in vitro deposition using Aeroliser, Handihaler and Rotahaler devices. The performance of the SS-lactose formulations differed across the grade of lactose and amount of fine lactose used compared to the same powder compositions blended with SX. SX had a greater fine particle fraction than SS for most of the comparable formulations, probably because of the different cohesiveness of the drugs. A head-to-head comparison of 'matched' SX and SS formulations when aerosolised from the same three devices demonstrated that formulation-device interactions are as critical in determining the in vitro deposition of drug-lactose blends as the identity of the active pharmaceutical ingredient. This work has revealed the limitations of the interpretative value of published in vitro performance data generated with a single device (even at equivalent aerosolisation force), when designing formulations for a different device.
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London SE19NH, UK; Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, London SE19NH, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Muddle
authors.affiliation: Department of Pharmacy, University of Hertfordshire, Hatfield AL109AB, UK.
authors.forename: Darragh
authors.initials: D
authors.lastname: Murnane
authors.affiliation: Department of Pharmacy, University of Hertfordshire, Hatfield AL109AB, UK.
authors.forename: Irene
authors.initials: I
authors.lastname: Parisini
authors.affiliation: Department of Pharmacy, University of Hertfordshire, Hatfield AL109AB, UK; MedPharm Ltd, R&D Centre, Units 1 and 3 Chancellor Court, Surrey Research Park, Guildford GU2 7AB, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Brown
authors.affiliation: Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, London SE19NH, UK.
authors.forename: Clive
authors.initials: C
authors.lastname: Page
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London SE19NH, UK. Electronic address: ben.forbes@kcl.ac.uk.
authors.forename: Ben
authors.initials: B
authors.lastname: Forbes
mesh_terms: D000280:Administration, Inhalation; D000420:Albuterol / Q000008:administration & dosage* / Q000737:chemistry; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000737:chemistry; D058995:Dry Powder Inhalers / Q000295:instrumentation / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D007785:Lactose / Q000737:chemistry*; D010316:Particle Size; D013431:Sulfates / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D001993:Bronchodilator Agents; D005079:Excipients; D013431:Sulfates; D007785:Lactose; D000420:Albuterol
keywords: aerosols; content uniformity; excipients; formulation; particle size; powder technology; pulmonary drug delivery