In Vitro Drug Delivery Performance of a New Budesonide/Formoterol Pressurized Metered-Dose Inhaler
- 1 June 2009
- journal article
- research article
- Published by Mary Ann Liebert Inc in Journal of Aerosol Medicine and Pulmonary Drug Delivery
- Vol. 22 (2), 113-120
- https://doi.org/10.1089/jamp.2008.0697
Abstract
A combination of the corticosteroid budesonide and the long-acting beta2-adrenergic agonist formoterol is available in the United States in a single hydrofluoroalkane pressurized metered-dose inhaler (pMDI) for treatment of persistent asthma. The in vitro performance of the product, including delivered dose uniformity, aerodynamic particle size distribution, and dose proportionality, was evaluated. Both marketed formulations of the product were assessed (budesonide/formoterol 80/4.5 microg and 160/4.5 microg). Delivered dose was determined throughout the canister life using an automated dose delivery test method, and aerodynamic particle size distribution was evaluated using an Andersen Cascade Impactor-both in six batches of the product. Proportionality was assessed in 16 batches across three formulation strengths of budesonide, including a development formulation of 40/4.5 microg. Budesonide/formoterol pMDI provided a consistent delivered dose, with a mean value within +/-15% of the label claim for both actives. All individual results were within +/-20% of label claim. Mean fine particle dose (dose fraction <4.7 microm) was 59 and 68% for budesonide and formoterol, respectively. Delivered dose of budesonide was proportional to labeled dose, and fine particle dose was slightly less than proportional. Changes in budesonide content did not affect formoterol dose. Budesonide/formoterol pMDI provides a consistent delivered dose with an appropriate respirable fraction for therapeutic effectiveness. The product satisfies the performance requirements of current U.S. pharmacopeial and regulatory standards for pharmaceutical pMDI products.Keywords
This publication has 11 references indexed in Scilit:
- Twelve-week, randomized, placebo-controlled, multicenter study of the efficacy and tolerability of budesonide and formoterol in one metered-dose inhaler compared with budesonide alone and formoterol alone in adolescents and adults with asthmaClinical Therapeutics, 2007
- Efficacy and Safety of Budesonide and Formoterol in One Pressurised Metered-Dose Inhaler in Adults and Adolescents with Moderate to Severe AsthmaDrugs, 2006
- Modulite®: A Simple Solution to a Difficult ProblemRespiration, 2005
- Characterization of suspension-based metered dose inhaler formulations composed of spray-dried budesonide microcrystals dispersed in HFA-134a.Pharmaceutical Research, 2004
- Effects of bronchodilator particle size in asthmatic patients using monodisperse aerosolsJournal of Applied Physiology, 2003
- Performance of Large- and Small-Volume Valved Holding Chambers with a New Combination Long-Term Bronchodilator/Anti-inflammatory Formulation Delivered by Pressurized Metered Dose InhalerJournal of Aerosol Medicine, 2002
- Pharmaceutical transition to non-CFC pressurized metered dose inhalersRespiratory Medicine, 2000
- Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclomethasoneEuropean Respiratory Journal, 1998
- Optimal particle size for beta 2 agonist and anticholinergic aerosols in patients with severe airflow obstruction.Thorax, 1996
- Deposition of particles in the human respiratory tract in the size range 0.005–15 μmJournal of Aerosol Science, 1986