Introduction

Combination of inhaled corticosteroids (ICS) and long acting ?2 agonists (LABAs) have been shown to improve the pulmonary function with reduction in the rate of exacerbations. Inhalation is the preferred mode of administration of asthma and COPD medications since it delivers the drugs directly into all the sites of lung inflammation including peripheral airways. The clinical efficacy of fixed combination formulation of beclomethasone dipropionate (BDP) and formoterol (100/6 µg) both dissolved in a hydrofluoroalkane (HFA) propellant and delivered by pressurized metered dose inhaler (pMDI) has been reported in a few studies. However, its lung deposition pattern remains to be investigated.

Aim

The lung deposition and lung distribution of the fixed extrafine combination of BDP/formoterol was evaluated in healthy subjects, asthmatics and chronic obstructive pulmonary disease (COPD) patients. This study also assessed how the in-vitro characteristics of the formulation translate into the in-vivo performance in asthma and COPD.

Methods

Study design

• Open-label, single-dose, parallel-group, non-randomized study
• each patient received a single treatment of 4 puffs of BDP/formoterol HFA combination delivered by pMDI attaining a total dose of 400 µg BDP and 24 µg formoterol
• the total cohort comprised of 8 healthy subjects, 8 asthmatics and 9 COPD patients
• The formulation was labelled with ^99mTechnetium (^99mTc), prior to inhalation

Endpoints

• Correlation between particle size distribution of radioactivity and of the drugs in the formulation
• Intra- and extra-pulmonary deposition
• Amount of exhaled drug
• Central/peripheral ratio (C/P)
• Forced expiratory volume in 1 sec (FEV1) upto 24 hours post-dose
• Pharmacokinetic parameters upto 24 hours post-dose

Results

• Particle size distributions of both unlabeled and labeled BDP/formoterol formulations were in close agreement
• The lung deposition and C/P ratios in the groups are shown in figure 1.

• All the groups demonstrated increase in FEV1. However, a more evident bronchodilator effect was observed in the asthma and COPD groups

Conclusion

The beclomethasone dipropionate (BDP)/formoterol extrafine formulation was efficiently delivered to the lungs and resulted in high drug deposition and homogenous distribution of BDP and formoterol throughout the airways, irrespective of the pathophysiology and lung function.

J Aerosol Med Pulm Drug Deliv. 2010 Jun;23(3):137-48. Doi: 10.1089/jamp.2009.0772.