Breathing Simulators: One step closer to representative deposition profiles?

Maria Palha, Sofia Silva, Isabel S. Lopes, Eunice Costa

Cascade impactors are widely used for aerodynamic performance testing of dry powder inhalers (DPIs). Impactors are useful and efficient tools for quality control of inhalation products as well as for formulation development as a simple in vitro assessment of the deposition of the drug in the respiratory tract. However, the current USP pharmacopeia method considers a non-physiological representation of the human mouth-throat, the induction port, and a constant flow during testing. The flow achieves a 4 kPa pressure drop and an inhalation volume of 4 L, which does not account for the variability inherent in the patient population when evaluating product performance [1].
The main goal of this work was to compare the recently developed breathing pattern simulator and the Alberta Idealized Throat (AIT) [2], with the current pharmacopeia standard in the aerodynamic performance assessment. Three different setups operating under pharmacopoeia conditions, mimicking a square wave breathing profile, were tested: Fast Screening Impactor (FSI) + Induction Port (IP); FSI + AIT; FSI + AIT + Breathing Simulator (BRS). The two parameters evaluated, Emitted Dose (ED) and Fine Particle Dose (FPD), were relatively insensitive to test conditions when comparing the three setups, with the FSI + AIT + BRS improving reproducibility. In addition, three different breathing patterns were evaluated: medium, strong and weak, as defined in the literature [1]. These patterns represent inhalation profiles derived from patient measurements and capture different target patient populations. It was observed that BRS reduced method variability and that the square and medium profiles yielded the same results. In relation to the weak profile, a reduced FPD was observed, most probably due to insufficient powder dispersion. In relation to the strong inhalation profile, the ED was higher but no differences were observed in terms of the FPD in comparison to the medium and square waves profiles.

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