Summary

In dry powder inhaler (DPI) formulations, it is important to understand if newly engineered carrier and drug particles have the necessary characteristics to achieve the desired performance. Therefore, it was the objective of this work to understand how distinct particle characteristics of various lactose grades presenting distinct solid-states, particle size distribution (PSD) and morphologies could potentially influence powder bulk properties and thereby affect the DPI performance. Low-dose blends of salbutamol sulphate (SS) with the distinct lactose particles were prepared and their in-vitro aerodynamic performance investigated using different device types (capsule v/s. reservoir) at increasing airflow rates (28,60 and 100 L/min). To derive insights into the influence of the various particle and bulk properties on the parameters derived in-vitro a multivariate statistical analysis was carried out. Likewise, it was shown that when different aerosolization mechanisms and airflows are at work dissimilar forces act on the formulations resulting in distinctive particle and bulk properties impacting the in-vitro aerodynamic performance. Generally, it was apparent that in combination with a capsule-based device, carriers with smaller particle size (Dv_0.5 ≈ 50 µm) and a certain fraction of fines (about 10%) are less susceptible to different airflows. For certain reservoir devices, excipient particles with a larger particle size (Dv_0.5 ≥ 130 µm) might be more advantageous.

Key Message

A combinational approach using multivariate analysis and in-vitro characterization showed that carriers with smaller particle size and a certain fraction of fines are less susceptible to different airflows, when capsule-based devices are used. For certain reservoir devices, excipient particles with a larger particle size might be more advantageous