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Inhalation JUNE 2020 15 Aerosol deposition in the lungs Several studies have explored the principal factors determining the efficacy of aerosol delivery to the lungs. As early as 2008, Bhashyam, et al 27 described, in a bench study, the effect of infant, pediatric and adult gas ow rates and set-ups on the droplet size and location of deposition within the circuit as well as the delivered dose. e general trend was seen to be that increasing gas ow rate reduced the dose available for inhalation. Additionally, smaller internal diameter nasal cannula select for smaller droplets exiting the system. Both of these e ects were most likely due to inertial impaction losses throughout the circuit. Sub- sequent studies in animal and human models veri ed these results and validated the utility of bench models in predicting the dose delivered in vivo. 28, 29 Additional bench studies have assessed the effect of other variables such as position in the circuit and input droplet size, 30 as well as breathing pattern 23, 31 on HFNT aerosol delivery. Interestingly, distressed breathing was seen to increase the delivered dose. is suggests more e cient entrainment of aerosol in the breath, or the potential for e cient delivery at applied gas ow rates that closely match the peak inspiratory ow or the ratio of administered gas ow to peak inspiratory ow rate. 32 Findings from these studies have found application in the delivery of perhaps non-obvious therapeutics such as lidocaine as an airway analgesic during awake ber optic intubation. 33 aerosol is delivered, however, it is likely that the low dose delivered, even after several pMDI actuations, is not a practical clinical solution. 24 A randomized, crossover, single-photon emission computed tomography study in adults indicated that VMN devices deliver more to the lung than com- pressor-driven jet nebulizers (JN) at the clinically relevant 30 liters per minute applied gas ow rate. 25 Nevertheless, there are currently no clinical outcome studies comparing compressor-driven jet nebulizers to vibrating mesh nebulizers. However, the performance of both has been shown to deliver levels of aerosolized drug that provide comparable bene t to that seen in patients using a hand-held nebulizer during sponta- neous breathing. 18, 22 In the clinical setting, depending on physician prefer- ence, devices available locally, institutional protocols and patient requirements, aerosol may be presented to the patient, but by means of a nebulizer not included in the HFNT system itself. In these instances, JN and VMN in combination with both mouthpiece and facemask are often put to use. A recent bench study evaluated aerosol delivery across combinations of these drug delivery interfaces with and without concurrent HFNT. 26 Across the test combinations, the VMN plus mouthpiece was seen to deliver the highest amount of aerosol, with combinations of concurrent HFNT facilitating delivery of some aerosol, but generally low amounts compared to nebulizer alone. LEARN MORE: www.proveris.com contactus@proveris.com +1 508 460-8822 Scientific expertise and testing strategies for innovator and generic OINDPs • Human Usage Studies • Device Selection • Formulation Screening Alternative BE Studies • Regional Drug Deposition • Plume Velocity • Evaporation Fraction • In Vitro Testing • Drug Product Characterization Studies • Priming/Repriming • Temperature Cycling • Device Robustness • Stability Studies • Batch Release Testing • Long-term Stability Testing • Root Cause Analysis • OOS/OOT Investigation FROM DEVELOPMENT TO COMMERCIALIZATION YOUR PARTNER… NOW FEATURING cGMP COMPLIANT LABORATORY