Effects of a novel roflumilast and formoterol fumarate dry powder inhaler formulation in experimental allergic asthma.

In this study we aimed to develop a roflumilast (R) and formoterol fumarate (F) dry powder inhaler formulation (DPI) incorporating HPβCD by spray drying and evaluated if it attenuates the inflammatory process and improves lung function in a murine model of ovalbumin induced allergic asthma. The DPI was characterized by powder X-ray diffraction, thermal analysis, scanning electron microscopy, particle size, density, specific surface area and dynamic vapor sorption analyses. In vitro deposition studies were performed using a NGI, while transepithelial permeability and in vivo effects on lung mechanics and inflammation in a model of allergic asthma were also assessed. The R:F formulation was amorphous with high glass transition temperatures, comprised of wrinkled particles, had low bulk and tapped densities, high surface area, suitable particle size for pulmonary delivery and exhibited no recrystallization even at high relative humidities. MMAD were statistically similar of 4.22 ± 0.19 and 4.32 ± 0.13 µm for F and R, respectively. Fine particle fractions (<5 µm) were of more than 50% of the emitted dose. The R:F formulation led to reduced eosinophil infiltration and airway collagen fiber content, yielding decreased airway hyperresponsiveness. In the current asthma model, the R:F formulation combination decreased inflammation and remodeling, thus improving lung mechanics.