Effect of throat models and representative deposition profiles on the performance of carrier-based formulations
Sofia Silva1, Maria Palha1, Andreia Costa1, Ruben Chaves1 & Eunice Costa1
1Hovione FarmaCiencia SA, Sete Casas, 2674-506 Loures, Portugal
Summary
Aerodynamic particle size distribution (APSD), in combination with dose uniformity, are useful and efficient metrics to verify the quality of Dry Powder Inhaler (DPI) products. These compendial methods provide a precise and robust representation of the human throat and upper airway for testing purposes in the context of product quality control. However, the current USP pharmacopeia method considers a non-physiological representation of the human mouth-throat, the USP Throat, and a constant flow during testing. The flow achieves a 4 kPa pressure drop and an inhalation volume of 4L, which does not account for the variability inherent in the patient population.
The main goal of this work was to compare the recently developed Alberta Idealized Throat (AIT) and the Breathing Pattern Simulator (BRS) with the current pharmacopeia standard in the aerodynamic performance assessment of a model DPI formulation while applying a square wave profile. Furthermore, the comparison of these new developed technologies with additional collection surface coating, mimicking the particle impaction that occurs in vivo, was also performed. The Emitted Dose (ED) was generally unaffected by the type of set up or method conditions used. However, the Fine Particle Fraction (FPF) parameter increased when replacing the USP throat by the AIT, and decreased when using the BRS. Finally, different breathing patterns were evaluated using a non-coated AIT, namely profiles mimicking a patient with moderate COPD and another with severe COPD. In both profiles a decrease in the Fine Particle Dose (FPD) was observed when comparing to the standard square wave profile, most probably due to insufficient powder dispersion. This study clearly emphasized the need for using more bio-relevant approaches in investigating drug deposition during DPI product development.
