Novel dry powder inhalation system based on dispersion of lyophilisates

Dry powder inhalers and dry powder formulations experience a growing interest and are the subject of continuous further development. In this study the objective was to evaluate the possible aerosolization of lyophilisates by an air impact and to prove this new concept of creating individual inhalable particles from a coherent bulk at the time of inhalation. Therefore an output test system for disintegration of the lyophilisate and for delivery of the generated fine particles was developed. The output system uses compressed air at a preselectable pressure for reproducible generation of inhalable particles. In order to understand the aerosolization of lyophilisates by the air impact, different single excipient formulations of amino acids and sugars were investigated. Besides the characterization of the different formulations by microscopy and X-ray diffractometry, we focused mainly on the particle size distributions (PSD) of the dispersed particles. Thereby the geometric PSD was analyzed by laser diffraction, whereas the aerodynamic PSD was characterized by time of flight and Andersen cascade impactor analysis. The destruction of the porous structure of the lyophilisates resulted in large geometric particle sizes but aerodynamic particle sizes in the inhalable range with relatively large fine particle fractions (FPF) between 20% and 50% calculated as a percentage of the metered dose. Despite potential differences in freezing behavior and thus cake structure within lyophilization batches, we attained reproducible fine particle fractions. Overall, it is concluded that the controlled disintegration of lyophilisates into inhalable particles by an air impact is possible and substantial FPF are achieved. Therefore, the method represents a promising new dry powder inhalation technology.