PURPOSE: Nebulizer performance and efficiency has typically been measured by Delivered Dose (DD), Mass Median Aerodynamic Diameter (MMAD), Respirable Fraction (RF%) and Total Output Rate (TOR). It's since been shown that both Respirable Dose (RD) and Respirable Drug Delivery Rate (RDDR) are also important measures to compare nebulizer efficiency. The aim is to compare in-vitro performance and efficiency of 3 commercially available breath-enhanced nebulizers by measuring RD, RDDR, MMAD and nebulization time with budesonide inhalation suspension (Pulmicort Respules®, AstraZeneca, Wilmington, DE).
METHODS: Particle size distribution was measured via cooled NGI (Next Generation Impactor, 17°C) flow rate 30l/m. Budesonide (250μg/ml) fill volume 2.0mL was nebulized in LC® Sprint Reusable Nebulizer (PARI, Midlothian, VA), LC® PLUS Reusable Nebulizer (PARI), and Sidestream Plus reusable nebulizer (Respironics, Murraysville, PA). 1.2bar compressed air supply (PARI PRONEB® Ultra II [USA]/PARI BOY [EU]) was used. Breath simulation performed via PARI COMPAS: tidal volume 500ml, 15 breath/min, I:E 50: 50 to investigate nebulization time and DD. Inspiratory filters were exchanged once after 2 minutes. The amount of budesonide on inspiratory filters and in nebulizer residue was assayed from inspiratory filters using a validated internal standard HPLC-UV method. RD and RDDR were calculated as follows: RD=Respirable Fraction(RF=%droplets<5μm) × Delivered Dose (DD=Drug on both inspiratory filters). RDDR=Respirable Fraction (RF=%droplets<μm) × Drug on first inspiratory filter/2minutes.
RESULTS: Nebulizer RD<5μm [μg] Neb time [min] MMAD [μm] RDDR[μg/min]LC SPRINT 49.8 4.9 5.0 12.8 LC PLUS 53.8 6.0 5.3 9.6 Sidestream Plus 40.4 6.0 5.9 6.9.
CONCLUSION: RDDR is highest with LC® Sprint(p<0.05) and 46% higher compared to Sidestream Plus. Treatment time is shortest for LC® Sprint, followed by similar values for Sidestream Plus and LC® PLUS. LC® PLUS RDDR is 39% higher and RD is 33% higher than Sidestream Plus LC® Sprint RDDR is 25% higher than LC® PLUS, and there is no significant difference in RD.
CLINICAL IMPLICATIONS: RDDR is an important measurement to ensure patients receive clinically effective doses. As a reference, LC® PLUS was used in the pivotal clinical trials to prove safety and efficacy for Pulmicort Respules®. Therefore, further investigation is warranted to evaluate clinical implications of using less efficient nebulizers with current aerosol medications.
DISCLOSURE: Lisa Cambridge, No Financial Disclosure Information; No Product/Research Disclosure Information