Real life dose emission characterization using patient inhalation profiles

The aerodynamic characteristics of the dose emitted from dry powder inhalers (DPIs) varies from patient to patient depending on their peak inhalation flow (PIF) and may also be affected by other factors such as the inhaled volume (Vin) and the initial acceleration of the inhalation manoeuvre (ACIM). Compendial methods for the in-vitro determination of the dose emitted from inhalers recommend using a vacuum pump to simulate an inhalation but this is not representative of that made by a patient. In this study a new in-vitro methodology has been developed by adapting a mixing inlet with the Andersen Cascade Impactor (ACI) to use COPD patient inhalation profiles in place of a vacuum pump. The aim was to investigate the effect of inhalation manoeuvre parameters (PIF, Vin and ACIM) on the dose emission performance of both Symbicort® Turbuhaler® and DuoResp® Spiromax®. The medium (200 μg/6 μg budesonide[BUD]/formoterol[FORM]) and high strength (400 μg/12 μg BUD/FORM) products have been used.
In the first part of this thesis a comparison has been made between the Alberta Idealised Throat (AIT) and the traditional USP Induction Port (IP) using standard in-vitro compendial methodology. The medium strength version of the Symbicort® Turbuhaler® was used. The results show that the AIT captured more drug compared to the USP IP throat (p<0.05). Regardless of the inhalation volume, no significant change was observed for the FPD at 28.3 L/min between the two throats, although there was a significant difference in the FPD when the flow was increased to 60 L/min (p<0.05). In contrast to an inhalation flow of 28.3 L/min, at 60 L/min the MMAD reduced significantly (p<0.05). No significant change was observed for TED at both inhalation flows while changing the size of the throats regardless of the inhalation volume.
In the second and the last but major part, the performance of the Symbicort® Turbuhaler® and DuoResp® Spiromax® was evaluated using the medium and high strength products. The results of both inhalers indicate the importance of PIF on the dose emission characteristics as it increased from <30 to >60 L/min. As a result, both FPD and TED increased and MMAD decreased significantly (p<0.05). The Vin and ACIM showed different effects on the medium and high strength of both inhalers. Generally, Vin had a small effect on both FPD and TED which increased and no change was observed with MMAD. The ACIM also had a small impact on FPD, TED and MMAD for Symbicort® Turbuhaler® and only FPD and MMAD for DuoResp® Spiromax®.
The results highlights the potential of this methodology to characterise the dose a patient receive during real life use by using these inhalation profiles in place of the inhalation provided by a vacuum pump. Overall, PIF was the dominant inhalation manoeuver parameter for the dose emission from the Symbicort® Turbuhaler® and DuoResp® Spiromax®.