Dose Emission Characteristics of Placebo PulmoSphere®Particles Are Unaffected by a Subject's Inhalation Maneuver

Abstract

Good compliance to the prescribed dosing regimen and inhaler instructions for use are critical for asthma/chronic obstructive pulmonary disease (COPD) patients to achieve good control of their disease. We investigated the extent to which a system comprising porous particles delivered with a passive dry powder inhaler could be designed to achieve significant reductions in dose inhalation errors. Porous placebo particles were prepared by an emulsion-based spray-drying method (PulmoSphere® technology). The formulations were administered as dry powders with a portable, blister-based dry powder inhaler (Simoon Inhaler). The inhalation profiles of 69 asthma/COPD subjects were determined with an inhaler simulator with resistance comparable to that of the Simoon Inhaler. Powder emptying from the device was assessed by laser photometry. Aerosol performance was assessed on a Next Generation Impactor, and with the idealized Alberta mouth-throat model using both square-wave and subject-inhalation profiles generated in the breathing study. Virtually all subjects could achieve a pressure drop of at least 1 kPa and an inhaled volume of at least 500 mL with the Simoon Inhaler. In vitro measures of particle deposition were found to be largely independent of the inhalation maneuver (flow rate, inhaled volume, ramp time) across the broad range of inhalation profiles observed in the breathing study. The rapid emptying of powder from the Simoon Inhaler minimizes the impact of dose-related errors, such as failure to exhale before inhalation and failure to breath-hold post inhalation. Inertial impaction that is largely independent of a subject's inhalation maneuver can be achieved with a drug/device combination product comprising a porous particle formulation and blister-based inhaler.