Novel Pressurised Metered Dose Inhaler Aerosol Delivery of Fluticasone Propionate via Tempo® in Humans

Abstract

RATIONALE: Aerosol drug delivery by pMDI remains popular but problematic. Poor coordination, high oropharyngeal deposition and little peripheral airway deposition limit conventional MDIs. MAP has developed a novel pMDI (Tempo) which promises to overcome these limitations with a synchronous trigger, plume control and vortexing flow control chambers.METHODS: Fluticasone propionate (FP) studied via originator actuator and via Tempo: 1) In vitro particle size characterization at 28.3 and 45 L/min by Andersen Cascade Impactor. 2) In vivo inhaled 99mTc radiolabeled FP in 12 healthy volunteers in a randomized, crossover study.RESULTS: 1) Fine particle fraction at 28.3 and 45 L/min was 88.6% and 89.2% for Tempo FP versus 40.4 % and 43.1% for originator. 2.i) Oropharyngeal deposition was reduced from 76.8% (originator) to 18.3% (Tempo). 2.ii) Lung deposition increased from 13.8% (originator) to 41.5% (Tempo). 2.iii) Dose variability was reduced by 50% with Tempo.CONCLUSIONS: The Tempo system allows delivery at pre-specified time within an inspiratory maneuver; provides greater respirable proportion of metered dose; reduces oropharyngeal deposition resulting in greater absolute dose reaching peripheral lung, with greater consistency across a range of lung functions and inspiratory flows. Improved lung deposition and dose variability may allow higher payload and the use of more potent and narrow therapeutic range drugs requiring accurate biotargetting to be delivered by pMDI. Tempo clinical trials are underway to further confirm these findings. RATIONALE: Aerosol drug delivery by pMDI remains popular but problematic. Poor coordination, high oropharyngeal deposition and little peripheral airway deposition limit conventional MDIs. MAP has developed a novel pMDI (Tempo) which promises to overcome these limitations with a synchronous trigger, plume control and vortexing flow control chambers. METHODS: Fluticasone propionate (FP) studied via originator actuator and via Tempo: 1) In vitro particle size characterization at 28.3 and 45 L/min by Andersen Cascade Impactor. 2) In vivo inhaled 99mTc radiolabeled FP in 12 healthy volunteers in a randomized, crossover study. RESULTS: 1) Fine particle fraction at 28.3 and 45 L/min was 88.6% and 89.2% for Tempo FP versus 40.4 % and 43.1% for originator. 2.i) Oropharyngeal deposition was reduced from 76.8% (originator) to 18.3% (Tempo). 2.ii) Lung deposition increased from 13.8% (originator) to 41.5% (Tempo). 2.iii) Dose variability was reduced by 50% with Tempo. CONCLUSIONS: The Tempo system allows delivery at pre-specified time within an inspiratory maneuver; provides greater respirable proportion of metered dose; reduces oropharyngeal deposition resulting in greater absolute dose reaching peripheral lung, with greater consistency across a range of lung functions and inspiratory flows. Improved lung deposition and dose variability may allow higher payload and the use of more potent and narrow therapeutic range drugs requiring accurate biotargetting to be delivered by pMDI. Tempo clinical trials are underway to further confirm these findings.