Lung Deposition of the Dry Powder Fixed Combination Beclometasone Dipropionate Plus Formoterol Fumarate Using NEXThaler ® Device in Healthy Subjects, Asthmatic Patients, and COPD Patients.

Background: This study evaluated the lung deposition and the distribution pattern in the airways of a fixed combination of beclometasone dipropionate (BDP) and formoterol fumarate (FF) (100/6g) delivered as an extrafine dry powder formulation (mass median aerodynamic diameter, MMAD (m) BDP=1.5; FF=1.4) through the NEXThaler((R)) device in healthy subjects, asthmatics, and patients with COPD. Methods: Healthy subjects (n=10), asthmatic patients (n=9; 30%FEV1 < 80%), and COPD patients (n=9; FEV1/FVC 70%, 30%FEV1 < 50%) completed this open-label, single administration (inhalation of four actuations) parallel group study. After inhalation of Tc-99m-radiolabeled BDP/FF combination (radiolabeled BDP + unlabeled FF), the drug deposition was assessed using a gamma-scintigraphy technique. Patients' lung function was assessed. Results: No significant difference in drug deposition was observed between the three study groups. Mean lung deposition, extrathoracic deposition, and amount exhaled ranged, respectively, between 54.9% and 56.2%, between 41.8% and 43.2%, and between 1.6% and 3.3% of BDP emitted dose (71.72.5g) for the three study groups. The central to peripheral ratio (reflecting the lung distribution pattern) ranged between 1.23 and 2.02 for the three study groups, indicating a distribution of the drug throughout the airways, including periphery. The study treatment produced a forced expiratory volume in one second (FEV1) increase over time, reaching a maximum improvement generally within 1-4 hours. Conclusions: The fixed extrafine dry powder combination BDP/FF (100/6g) administered through the DPI NEXThaler((R)) achieved similar intrapulmonary deposition in healthy subjects, in asthmatic patients, and COPD patients (approximately 55% of emitted dose) irrespective of the underlying lung disease with a negligible amount of exhaled particles. The study showed high reliability of the device, reproducible dosing, and distribution throughout the lungs. The results supported the concept of efficient delivery of the combination to the target pulmonary regions, thanks to the extrafine formulation. FEV1 profile confirmed a relevant pharmacodynamic effect of the product.