Spray dried formulations for pulmonary delivery – challenges in filling, aerosol generation and delivery
Regina Scherließ1, Angelika Jüptner1, Marie Hellfritzsch1, Camille Kaj², Ségolène Sarrailh², Gerallt Williams²
1Department of Pharmaceutics and Biopharmaceutics, Kiel University, Grasweg 9a, 24118 Kiel, Germany
2Aptar Pharma, Route des Falaises, 27100 Le Vaudreuil, France
Spray dried formulations are increasingly gaining attention in the field of inhalation. By this technique uniform dry powder particles suitable for inhalation without further processing can be created. However, spray dried powders also generate a lot of challenges due to their characteristics. In this study the interplay between spray dried formulation, filling equipment and inhalation device was evaluated to point out these challenges. Two different spray dried model formulations (target x50 < 5 µm) comprising mannitol as matrix without or with addition of leucine, respectively, and a blue dye as model API were prepared and characterised. For comparison an interactive blend was manufactured. Results showed that all spray dried formulations are of low bulk density and high specific surface area. Due to their small size, flowability is typically impaired resulting in a highly cohesive material which cannot be filled with a vacuum drum, but with a dosator. The addition of leucine increases flowability (determined as ffc) which is in favour for capsule filling with a vacuum drum equipment but detrimental for dosator filling. Furthermore, an addition of leucine helps to increase the emitted dose and reduces adhesion at the inner surfaces of a capsule-based device (Twister ®). Further aspects of this study include assessment of other DPI devices, evaluation of the effect of different filling procedures on aerodynamic properties and will also look at spay dried formulations for nasal delivery.