<i>In Vitro</i> Drug Delivery Performance of a New Budesonide/Formoterol Pressurized Metered-Dose Inhaler

Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.