Use of a Test Rig Allows Standardization of In Vitro Respirable Dose Testing with VHCs When Incorporating Short Delays Between Actuation and Inhalation

Dirk Von Hollen


It is important to provide relevant in vitro test data concerning the performance of drug delivery devices under simulated clinically relevant conditions, to guide device selection. An in vitro test system designed to allow the determination of respirable delivered dose (fine particle dose;FPD < 5µm) from valved holding chambers (VHCs) following a short delay between pressurized metered dose inhaler (pMDI) actuation and simulated inhalation was tested using two brands of VHC and two pMDI bronchodilator drug formulations. Twenty VHCs of each brand (OptiChamber Diamond and AeroChamber Plus Flow-vu; OCD and ACPFv) were tested with each pMDI bronchodilator brand/formulation (Ventolin 100µg and ProAir 90µg) with a delay of 0s and 2s. A next generation impactor was combined with an in vitro test rig with a flow of 30 L/min. Following pMDI shake and actuation a microphone attached to the pMDI actuator allowed diversion of the flow via the VHC within [delay + <0.1s] of pMDI actuation. Ten actuations were made into each of 5 VHCs for each time delay and pMDI drug brand/formulation. NGI cups were eluted for quantification by HPLC.   Respirable delivered dose as % label claim for each combination of test variables was; OCD[Ventolin-0s/2s=30.4/16.8] [ProAir-0s/2s=65.3/61.1], ACPFv[Ventolin-0s/2s=32.6/20.4] [ProAir-0s/2s=73.6/66.0]. Delay between pMDI actuation and inhalation resulted in a small difference in respirable delivered dose, but was outweighed by the large difference in respirable delivered dose due to choice of pMDI brand/formulation. There was only a small difference (<5µg) in respirable dose between VHC brands at 2s delay.

Key Message

 The respirable delivered dose from VHCs can be affected by a delay between pMDI actuation and inhalation, but selection of pMDI bronchodilator brand/formulation can affect the respirable delivered dose to a far larger extent than a 2 s delay.

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