Misty Max 10 nebulizer

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1 AirLife brand Misty Max 10 nebulizer Purpose Introduction Delivery of nebulized medication to the lungs is a complex process dependant upon a variety of clinical and device-related variables. Patient breathing patterns, the choice and dilution of drug nebulized, nebulizer flow rates, device selection and orientation all have the potential to affect the amount of drug delivered to the patient. In vitro (bench) testing can provide the end-user with useful information regarding nebulizer performance. Various test methods have been used over the years; however, the quantification of inhaled drug mass through the use of a simulated breathing patient has become an increasingly well-accepted method of evaluation. The use of a simulated breathing patient allows for a more accurate estimation of drug dose. 1 Medication delivery: Misty Max 10 nebulizer performance CareFusion conducted a study, the purpose of which was to compare the performance of four conventional small volume nebulizers (SVN) currently available on the market. The study was designed to closely simulate typical clinical conditions in the acute care setting. Conclusions The Misty Max 10 nebulizer creates finer particles with a tighter distribution than any of the other nebulizers tested. As a result, the respirable fraction performance of Misty the Max 10 nebulizer is significantly higher than that of competitive products. The Misty Max 10 nebulizer delivers significantly higher inhaled respirable mass than the other nebulizers when tested in the angled position. The Misty Max 10 and the VixOne nebulizers deliver significantly higher inhaled respirable mass than the other nebulizers when tested in the vertical position. There was no statistically significant difference between Misty Max 10 and VixOne nebulizer test results. (Continued on next page) Conventional SVN performance at 8 lpm flow AirLife brand Misty Max 10 nebulizer Westmed VixOne Hudson MicroMist Salter Labs 8900 Particle size MMAD GSD % Respirable (< 4.7 μm) % 2.08* %* 2.43* % 1.85* %* Inhaled mass performance: Treatment time (min) Total residual neb, t-piece, m.p. (μg) Inhaled respirable mass (μg) 1, , , , , * 1, , * 1, * 1, , * 1, * 1, Note: All drug masses expressed in micrograms of albuterol = Performance of nebulizer at vertical position = Performance of nebulizer at 60 degrees from vertical Comparisons were made using Student s T-test for means *Difference between MM10 statistically significant (p<.05) Difference between MM10 not statistically significant (p>.05)

2 The Misty Max 10 nebulizer delivers an averaged inhaled respirable mass approximately 14% higher than the closest competitor. The Misty Max 10 nebulizer has the lowest average drug residual volume compared to the other nebulizers tested. Performance criteria evaluated Respirable fraction This is the percent of aerosol generated by mass that falls below an aerodynamic diameter of 5μm. It has been reported that particles less than 5μm will penetrate beyond the upper airways and deposit into the tracheobronchial and pulmonary regions of the lung. 3 The closest cascade plate cutoff point of 4.7μm was utilized to quantify mass below 5μm. Respirable fraction % less than 4.7μm Misty Max 10 VixOne MicroMist 8900 This is an estimate of the amount of respirable drug inhaled by the patient under specified breathing patterns and duration. It is calculated by multiplying the respirable fraction and the total drug mass collected on the inhalation filter. Hess used a similar method of estimating respirable mass available to the patient. 4 Average inhaled respirable mass Drug mass (μg) Misty Max 10 VixOne MicroMist 8900 Treatment time This is the amount of time (minutes) to nebulize 3 ml of 0.083% albuterol solution. Average treatment time Minutes Misty Max 10 VixOne MicroMist 8900 Total residual This is the amount of drug mass found within the nebulizer, t-piece and mouthpiece after treatment. The drug mass within the nebulizer and accessories were assayed using a spectrophotometer. MMAD Mass median aerodynamic diameter (MMAD) is a measurement of central tendency of the size distribution of aerosol particles. It is the diameter, in micrometers, of which 50% of the mass of aerosol is larger and 50% is smaller. Drug mass (μg) d GSD Geometric standard deviation (GSD) is a measure of the width of the size distribution of aerosol. For log normal distributions, it is calculated as follows: GSD = (84.13% diameter/15.87% diameter). 1, Misty Max 10 VixOne MicroMist 8900

3 Test methods Particle size An Andersen eight-stage cascade impactor (ACI) with USP inlet was used and assayed with a spectrophotometer (277nm). Particle size characterization was performed using 3 ml of 0.083% albuterol solution and a nebulizer flow rate of 8 L/min. All cascade tests sampled nebulizer aerosol through the manufacturer s supplied t-piece and mouthpiece. Inhaled drug mass The test setup consisted of a filter placed between the mouthpiece of the nebulizer and a simulated breathing patient. The filter captured the inhaled aerosol exiting the mouthpiece and the drug mass deposited onto the filter was quantified with a UV spectrophotometer. A simulated breathing patient was created by using a NPB 7200 ventilator and a Michigan Test Lung. An adult breathing circuit was connected to a ventilator that drove one side of the test lung. A bar was connected to the opposing bellows, duplicating the movement of the test lung and simulating a patient breathing pattern. A BioTek flow analyzer was placed between the simulated patient and the inhalation filter to monitor actual breathing parameters. The breathing pattern was held at a tidal volume of approximately 500 ml, 12 breaths per minute and an I:E ratio of 1:2, similar to a study presented by Siafaka, Hess and Bigatello. 2 A commonly used dosing of albuterol (3 ml, 0.083% albuterol) was nebulized until aerosol production ceased for 30 seconds or after two minutes of sputtering was observed, whichever came first. All nebulizers were run at a flow rate of 8 L/min. Inhaled drug mass was collected onto the filter over the duration of treatment. Within the clinical setting, nebulizer treatments will be given to patients in a variety of incline positions. To better simulate these conditions, nebulizers were tested at both vertical and angled (60 ) positions. Products tested All nebulizers were randomly pulled from production lots. Catalog numbers chosen were of similar configuration: nebulizer, t-piece, mouthpiece, oxygen tubing and 6 flextube. A total of nine samples for each nebulizer were tested: three for particle size and six for inhaled drug mass testing. AirLife brand Misty Max 10 nebulizer (cat. no ) WestMed VixOne (cat. no. 0210) Hudson MicroMist (cat. no. 1883) Salter Labs 8900 (cat. no. 8900)

4 Technical data David A. Rivera, Research and Development February 17, 2004 The purpose of this document is to provide the in vitro performance characteristics of the AirLife brand Misty Max 10 nebulizer. In vitro measurements will help guide the end user as to the likelihood of effective delivery of inhaled medication to the lower respiratory tract Cascade impaction measures aerodynamic diameter directly, which accounts for the density and irregular shape of drug particles. It is believed that aerodynamic diameter more accurately predicts the behavior of aerosol as it is delivered into the patient s lungs. 6 Performance characteristics MMAD Mass median aerodynamic diameter GSD Geometric standard deviation Respirable fraction % < 4.7μm (by mass) Output rate (g/min) Treatment time 3 ml albuterol solution (min) Residual (g) Operating pressure (psi) 3 ml dose of 0.083% albuterol (μg) 5 L/min flow 10 L/min flow 2.21 ±0.07 (μm) 1.30 ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±14 2. There is more historical data on particle size measurement using cascade data than any other method. Relative comparison with historical data can be readily made. 3. Cascade impaction is one of the USP methods for characterization of particle distributions. 7 Particle size testing was conducted with components included with AirLife brand Misty Max 10 nebulizer : T-adapter, mouthpiece, 7 oxygen tubing and 6 flextube. The nebulizer was driven by compressed air (regulated to 50 psi) at 5 and 10 L/min flow. Ambient air, which flows through the open end of the T-adapter, was controlled at 50% ±10% relative humidity. For all cascade tests, the total mass of drug collected on all impactor stages and accessories were within 10% of initial dose. Definition of parameters measured 1. MMAD: Mass median aerodynamic diameter is a measure of central tendency of the size distribution of aerosol particles. It is the diameter, in micrometers, of which 50% of the mass of aerosol is larger and 50% is smaller. 2. GSD: Geometric standard deviation is a measure of the width of the size distribution of aerosol. For log normal distributions, it is calculated as follows 6 : Data presented: mean ±standard deviation Particle size An Andersen eight-stage cascade impactor (ACI) with USP inlet 6 was used and assayed with a spectrophotometer (277nm). Particle size characterization was performed using 3 ml of 0.083% albuterol in normal saline. Cascade impaction was chosen for the following reasons: GSD = (84.13% diameter/15.87% diameter). 5,6 3. Respirable fraction is the percent of aerosol generated by mass that falls below an aerodynamic diameter of 5μm MMAD. It has been reported that particles less than 5μm will penetrate beyond the upper airways and deposit into the tracheobronchial and pulmonary regions of the lung. 8 This measurement is often used to describe the quality of aerosol. 9 The closest cascade plate cutoff point of 4.7μm was utilized to quantify the mass below 5μm.

5 Output rate Nebulizers were weighed before and after aerosolizing a fill volume of 5 ml 0.083% albuterol for three min. Performance was reported in the average weight loss per minute (g/min). Testing was done with nebulizers randomly pulled from production lots. The nebulizer was operated with compressed air regulated to 50 psi, and 0.083% albuterol was the nebulized solution. Treatment time and residual The measurements of treatment time and residual will depend on the criteria used to determine the end of treatment. In clinical practice, it is common to tap the nebulizer near the end of the treatment to maximize the amount of drug nebulized. To simulate this practice, the nebulizer was periodically tapped when sputtering was observed for a maximum of two minutes or until tapping resulted in aerosol production for less than three sec. Treatment time was the total time required to nebulize 3 ml of solution. Residual was calculated by subtracting the weight of the nebulizer after the trial from the weight of the nebulizer empty. Treatment time and residual testing were done with nebulizers randomly pulled from production lots. The nebulizer was operated with compressed air and 0.083% albuterol was the nebulized solution. Operating pressure is an estimate of the quantity of respirable drug inhaled by the patient under typical clinical conditions. The concept of inhaled mass was originally introduced in 1991 by Smaldone 10 and has become a wellaccepted method for evaluating nebulizer performance. The test setup consisted of a filter placed between the mouthpiece of the nebulizer and a simulated breathing patient. The filter captured the inhaled aerosol exiting the mouthpiece and the drug mass deposited onto the filter was quantified with a UV spectrophotometer (277nm). To estimate the inhaled respirable mass, the drug mass deposited onto the filter was then multiplied by the corresponding respirable fraction. A simulated breathing patient was created by using a NPB 7200 ventilator and a Michigan Test Lung. An adult breathing circuit was connected to a ventilator that drove one side of the test lung. A bar was connected to the opposing bellows, thus duplicating the movement of the test lung, and thereby simulating a patient breathing pattern. A BioTek flow analyzer was placed between the simulated patient and the inhalation filter to monitor actual breathing parameters. The breathing pattern was held at a tidal volume of approximately 500 ml, 12 breaths per minute and an I:E ratio of 1:2, similar to a study presented by Siafaka, Hess and Biatello. 11 A commonly used dose of albuterol (3 ml, 0.083% albuterol) was nebulized until aerosol production ceased for 30 seconds or after two minutes of sputtering was observed, whichever came first. Collection of inhaled drug mass occurred over the duration of treatment. Testing was done with nebulizers randomly pulled from production lots. Product components used were from AirLife brand Misty Max 10 nebulizer : T-adapter, mouthpiece, 7 oxygen tubing and 6 flextube. Pressure was obtained from a T-connection between the compressed air flow meter and the nebulizer. Testing was done with nebulizers randomly pulled from production lots. Pressures at 5 and 10 L/min flow were evaluated while nebulizing 3 ml of 0.083% albuterol.

6 References 1 Dolovich, M. Assessing nebulizer performance. Respiratory Care, 2002; 47(11). 2 Siafake, A., Hess, D., Bigatello, L. Laboratory evaluation of new generation pneumatic nebulizers. 49th International Respiratory Congress, Abstracts 2003 Open Forum. Respiratory Care, Laube, B. In vivo measure of aerosol dose and distribution: Clinical relevance. Journal of Aerosol Medicine, 1996; 9(1). 4 Hess, D. Medication nebulizer performance. Chest, 1996: 110(2). 5 Consensus Statement: Aerosols and Delivery Devices. Respiratory Care, 2000; 45(6). 6 Hess, D. Medication nebulizer performance. Chest, 1996; 110(2): Aerosols. U.S. Pharmacopia, 23(601). 8 Laube, B. In vivo measurements of aerosol dose and distribution: Clinical relevance. Journal of Aerosol Medicine, 1996; 9(1). 9 Dolovich, M. Influences of inspiratory flow rate, particle size and airway caliber on aerosolized drug delivery to the lung. Respiratory Care, 2000; 45(6). 10 Smaldone, GC. Drug delivery via aerosol systems: Concept of aerosol inhaled. Journal of Aerosol Medicine, 1991; 4: Siafake, A., Hess, D., Bigatello, L. Laboratory evaluation of new generation pneumatic nebulizers. 49th International Respiratory Congress, Abstracts 2003 Open Forum. Respiratory Care, WARNING U.S. Federal Law restricts this device to sale by or on the order of a physician. Manufactured for: CareFusion Savi Ranch Parkway Yorba Linda, CA toll-free tel fax CareFusion France 309 S.A.S. 8 bis rue de la Renaissance F Châteaubriant, France 2011 CareFusion Corporation or one of its subsidiaries. All rights reserved. AirLife and Misty Max 10 are trademarks or registered trademarks of CareFusion Corporation or one of its subsidiaries. All other trademarks are property of their respective owners. RC2564 (0411/1000) L3384 Rev. A CareFusion Yorba Linda, CA carefusion.com