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Aerosol delivery to wheezy infants: a comparison between a nebulizer and two small volume spacers.

Inhalation therapy for wheezy infants with either a nebulizer or a pressurized metered-dose inhaler (pMDI) through a spacer is common practice. The aim of our study was to compare aerosol delivery to wheezy infants from a nebulizer and from a pMDI via two small volume spacers. Twenty wheezy infants (aged 4-12 months) were recruited. They inhaled salbutamol from a Pari-Baby nebulizer, from a detergent-coated Babyhaler, and from a Nebuchamber in random order. A filter was placed between the inhalation systems and the patients. The amount of salbutamol deposited on the filter was measured using an ultraviolet spectrophotometer and was expressed as a percentage of the total nebulized or actuated doses. The mean total nebulized dose for the Pari-Baby (1030 micrograms) was higher (P < 0.001) than the mean actuated dose from a pMDI for the Babyhaler (374 micrograms) and for the Nebuchamber (378 micrograms). Mean drug deposition on the filter was 40.2% (150 micrograms) of the total actuated dose for the detergent-coated Babyhaler and 40.7% (154 micrograms) of the total actuated dose for the Nebuchamber. There was no significant difference in drug deposition on the filter between the two spacers. Mean drug deposition on the filter was 25.3% (260 micrograms) of the total nebulized dose for the Pari-Baby nebulizer. There was no weight dependence in drug deposition on the filter for the two spacers, but, drug deposition increased with the subject's weight for the nebulizer. We have shown that aerosol delivery to wheezy infants from a pMDI through small volume spacers is effective and that a higher percentage of the total amount of salbutamol is delivered than from a nebulizer. The weight dependence in drug deposition for the nebulizer can be of clinical relevance.

Administration, Inhalation↗

Jet nebulization of PEI/DNA polyplexes: physical stability and in vitro gene delivery efficiency.

BACKGROUND: Aerosol drug delivery currently represents the most acceptable and convenient delivery system for repeated drug application to the lungs. Although polyethyleneimine (PEI) has recently been demonstrated to mediate gene transfer successfully to mouse lungs via aerosol delivery, the effect of the jet nebulization process on the properties of PEI/DNA polyplexes has not yet been examined. METHODS: PEI/DNA polyplexes were generated in several commonly used solvents, such as distilled water, HEPES buffered saline (HBS), and 5% glucose. The complex parameters, such as particle size, zeta potential, DNA integrity, and transfection efficiency, were examined before and after jet nebulization. RESULTS: The complex parameters and the transfection efficiency were influenced by the solvent that was used for complex formulation and by the nebulization process itself. When polyplexes were formulated in HBS, the particle size, zeta potential, and DNA concentration were affected by the nebulization process and the transfection efficiency decreased dramatically. Polyplexes formulated in 5% glucose were less susceptible to the nebulization process, as indicated by only minor changes of the zeta potential and particle size when compared with HBS. The resulting transfecion efficiency was very low both before and after nebulization. Polyplexes formulated in distilled water had the most resistant behavior with the nebulization process. Zeta potential, particle size, and DNA integrity were influenced least of all by nebulization. CONCLUSION: As a result, the transfection efficiency of PEI/DNA complexes remained constant throughout the nebulization process only when formulated in distilled water. These data suggest that distilled water represents the most appropriate solvent for polyplex formulation when delivered by jet nebulization.

Animals↗

Nebulization associated with bi-level noninvasive ventilation: analysis of pulmonary radioaerosol deposition.

UNLABELLED: Nebulization associated with noninvasive ventilation is used in emergency services and intensive care units. PURPOSES: To compare pulmonary radioaerosol deposition during jet nebulization associated to noninvasive ventilation versus spontaneous breathing nebulization; to measure the rate of lung depuration and the correlation between lung deposition, inspiratory flow and tidal volume (V(t)) using scintigraphy. SUBJECTS: Thirteen healthy volunteers (with normal spirometry), mean age (23.3+/-1.49) years, body mass index 21.2+/-2.3 kg/m(2). METHODS: Nebulization was performed in spontaneous breathing and associated with bi-level noninvasive ventilation (inspiratory pressure=12 cm H(2)O, expiratory pressure=5 cm H(2)O). The radioaerosol used in the nebulization was technetium (Tc99m) with diethylene triamine penta acetic acid, generated over a period of 9 min in a jet nebulizer. Analysis was performed through scintigraphy. Statistical analysis was performed by analysis of variance (for repeated measures), Bonferroni method, Student's t-test and Person's correlation. RESULTS: There was a decrease in radioaerosol lung deposition with nebulization associated to noninvasive ventilation (mean counts in spontaneous breathing 200,510+11,012 and mean counts in noninvasive ventilation 106,093+2811 (P<0.001). During spontaneous breathing nebulization there was a significant correlation between V(t) and radioaerosol deposition (r=0.565, P<0.05), also between inspiratory flow and radioaerosol deposition in the lungs (r=0.141, P<0.05). However, there was no correlation between V(t) and pulmonary deposition of radioaerosol in bi-level noninvasive ventilation nebulization (r=0.082). CONCLUSION: During nebulization with noninvasive ventilation in healthy volunteers, there was an increase in V(t) associated to a higher inspiratory flow rate, without resulting in a significant increase in pulmonary radioaerosol deposition.

Administration, Inhalation↗

The effect of formulation variables on the stability of nebulized aviscumine.

The pulmonary drug delivery of proteins present an alternative to parenteral and oral administration. Nebulization of aqueous protein solutions is an ideal method for pulmonary application of therapeutic proteins considering the difficulties of their formulation as MDIs or DPIs. This research presents the effect of variable excipients on the stability of freeze-dried aviscumine after reconstitution and nebulization. Formulations containing different lyoprotectants have been lyophilized and reconstituted with isotonic salt solution. The loss of aviscumine activity in the nebulizer reservoir and after nebulization with a PariBoy air-jet nebulizer, a Multisonic ultrasonic nebulizer and a Systam ultrasonic nebulizer was determined by a binding assay. The effect of variable lyoprotectants such as 8% (w/v) Dextran T1, HES130, HES450, HP-beta-CD and 6% (w/v) HES450 plus 2% (w/v) mannitol on the stability of aviscumine to air-jet and ultrasonic nebulization has been evaluated. Only 50% of aviscumine activity was retained after 20 min nebulization, where 8% (w/v) HES450 was shown to be the best stabilizer. Stabilization of aviscumine by the addition of variable surfactants as 0.01 and 0.1% (w/v) Poloxamer 188, 0.03 and 0.1% (w/v) PEG 8000, 0.03 and 0.1% (w/v) Solutol HS15 and 0.03 and 0.1% (w/v) octanoyl-N-methyl-glucamide to the reconstitution solution has also been studied. By the addition of 0.03% (w/v) octanoyl-N-methyl-glucamide, 70% of the activity was retained after 20 min nebulization.

Chemistry, Pharmaceutical↗

Contamination of nebulizers with environmental allergens.

BACKGROUND: A previous article described cockroach allergen in the nebulizer reservoir of an asthmatic patient who experienced a life-threatening exacerbation after nebulizer use. OBJECTIVE: To determine whether indoor allergens can be measured in home nebulizers. METHODS: As part of a large study examining nebulizer use in underserved asthmatic children, visiting nurses replaced nebulizer sets in patients' homes. Twenty used sets were randomly selected for analysis, without linkage to clinical or home environmental data. Nebulizer reservoirs and negative controls (buffer and albuterol) were extracted overnight with 2 mL of buffer. For positive controls, nebulizer sets were placed in homes with cats and dogs, and other reservoirs were intentionally contaminated with cat (Fel d 1), dog (Can f 1), cockroach (Bla g 1 and Bla g 2), and mouse (Mus m 1) skin test solutions. Extracts were tested for allergens in a masked manner using enzyme-linked immunosorbent assay. RESULTS: Of 17 reservoirs with adequate specimens for allergen detection, 5 (29%) had measurable levels for at least 1 of 5 allergens tested. One reservoir had measurable Can f 1, 2 had Bla g, 3 had Mus m 1, and none had Fel d 1 allergen. Two of 3 homes with cats where nebulizer setups were placed had measurable Fel d 1 in the reservoir, and 1 of 2 homes with dogs had measurable Can f 1. Reservoirs kept in sealed plastic bags had no detectable allergen. CONCLUSIONS: Indoor allergens can be found in the nebulizer equipment of children with asthma, with the potential for adverse consequences. Storing nebulizer sets in sealed plastic bags may prevent contamination.

Allergens↗

The role of domiciliary nebulizers in managing patients with severe COPD.

The difficulty of assessing nebulizer responses in chronic obstructive pulmonary disease (COPD) has been demonstrated before. This study aims to re-examine both the role of domiciliary nebulizers in COPD and also bronchodilator (BD) assessment in individuals. In a double-blind, randomized, cross-over trial, 19 stable patients with severe COPD were given the following medication 6-hourly for 2-week periods: (1) nebulized salbutamol 2.5 mg with ipratropium 0.5 mg and placebo inhalers (MDI) with spacer; (2) placebo nebules and inhaled salbutamol 400 microg with ipratropium 80 microg via MDI with spacer; (3) inhaled salbutamol 400 microg with ipratropium 80 microg via MDI with spacer (but no placebo nebulized drugs). Both nebulized and MDI drugs produced highly significant improvements in forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), specific airways conductance, 6-min walking distance (6MWD) and residual volume. There were no significant differences between BD responses obtained after active nebulized and active MDI BDs. From the diary cards, 2 weeks of active nebulized BDs produced a slightly higher median peak expiratory flow (PEF) than active MDI BDs (236 and 219 l m(-1), respectively, P=0.01) and slightly less extra inhaler use (0.8 and 1.1 puffs, respectively, P<0.05) but no significant difference in dyspnoea or quality of life (QOL) scores. There were significant correlations between domiciliary PEF and acute BD-induced changes in FVC and 6MWD, and also between domiciliary dyspnoea scores and acute changes in both total lung capacity and 6MWD. In conclusion, nebulized medication conferred little clinical advantage over the regular use of inhalers with spacers in this group of patients with severe COPD. However, acute changes in total lung capacity, FVC and 6MWD may be useful predictors of the longer-term effects of nebulized BDs in individual patients.

Administration, Inhalation↗

Nebulized beta2-agonist use in high-risk inner-city adults with asthma.

Nebulizer use has been linked to worse asthma outcomes, but the precise reason(s) for this relationship is not known. We assessed the frequency of nebulized beta2-agonist use in high-risk inner-city adults with asthma and compared asthma self-management practices according to nebulizer use in this population. This was a cross-sectional study conducted over 6 weeks from July to August 2000. A convenience sample (N=50) was recruited from an inner-city emergency department (ED). Adults (age > or = 18 years) were eligible if they had a physician diagnosis of acute asthma exacerbation. Data regarding asthma symptoms, acute care utilization, use of nebulized beta2-agonist for symptom relief, and indicators of asthma self-management (physician for asthma care, use of controller medications, current cigarette smoking, and substance use) were collected by an interviewer-administered survey. Nebulized beta2-agonist use was reported by 54.0% of patients during the 30 days before their ED visit. Nebulizer users reported more severe asthma symptoms (96.3% vs. 73.9% with moderate or severe persistent asthma, p=0.02) than nonusers. Nebulizer users were more likely to have a physician for asthma care (85.2% vs. 56.5%, p=0.02), have more frequent care from their physicians in the past 12 months (e.g., >3 visits: 59.3% vs. 30.4%, p=0.02), and notify their physician during their asthma exacerbation (39.1% vs. 7.7%, p=0.04). Compared with nonusers, nebulizer users reported better care across other indicators of care, though differences between groups were not significant. After accounting for symptom severity, results were largely unchanged. If these findings are confirmed in other studies with larger numbers of patients, we conclude that the relationship between nebulizer use and higher asthma morbidity largely represents preferential use of nebulizers by patients with more symptomatic disease.

Administration, Inhalation↗

Aerosol drug delivery using heliox and nebulizer reservoirs: results from an MRI-based pediatric model.

An MRI-based model of the mouth, throat, and upper airways of a 5-year-old boy is used to evaluate methods for increasing the nebulized drug dose delivered to the lungs. Four methods are considered: (1) standard nebulizer delivery with air, (2) delivery with 70/30 helium-oxygen (heliox), (3) delivery with air and an aerosol-conserving reservoir, and (4) delivery with heliox and a reservoir. When comparing air and heliox, delivery flowrates were adjusted so that the aerosols produced were of similar size. The reservoir utilized was the Medicator Aerosol Maximizer (Healthline Medical, Baldwin Park, CA). It conserves the aerosol generated by the nebulizer during exhalation and makes it available for the next inhalation. Technetium-DTPA was utilized. The standard nebulizer driven by air delivered 2.2% of the dose loaded into the nebulizer to the lungs as fine droplets, versus 3.3% for the nebulizer with heliox (50% increase; p = 0.002 vs. air), 2.9% for the nebulizer plus reservoir driven by air (32% increase; p = 0.02 vs. no reservoir), and 4.0% for the nebulizer plus reservoir driven by heliox (82% increase; p = 0.002 vs. air without reservoir). The increased pulmonary dose when heliox was utilized occurred because of decreased deposition within the nebulizer and other delivery equipment. The increased pulmonary dose when the reservoirs were utilized occurred due to a decrease in the dose expelled from the nebulizer by exhalation.

Administration, Inhalation↗

Bench testing of nebulizers: a comparison of three methods.

Although nebulizers can vary widely in performance, there is no uniformly accepted method for bench testing these devices. In the present study, we compared three bench methods of measuring the performance of three commercial jet nebulizers (Whisper Jet [WJ; Marquest Medical, Englewood, CO], Sidestream [SS; Marquest Medical], and Vixone [VO; Westmed, Tucson, AZ] to assess the impact of the method of testing on reported nebulizer performance. Each nebulizer was charged with 3 mL of albuterol mixed with a radiotracer (technetium [99mTc]), and the radioactivity captured on a paper filter was expressed as a percentage of the nebulizer charge (% delivered). The nebulizers were tested with and without duplication of spontaneous respiration by a piston pump (spontaneous respiration and standing cloud methods, respectively). The nebulizers were also tested using a model of mechanical ventilation (mechanical ventilation method). For all three devices, the addition of the standardized breathing pattern significantly reduced the % delivered with all three nebulizers compared with the standing cloud method. For the standing cloud method, the presence of the T-piece/mouth-piece significantly reduced the % delivered with the WJ but not with the other two devices. The mechanical ventilation method had the lowest % delivered for all three devices. The magnitude of the differences between nebulizers varied with duration of treatment. The findings of this study emphasize the importance of bench testing that duplicates intended clinical usage, because significant differences in nebulizer performance may be manifested under certain clinical conditions but not under others.

Administration, Inhalation↗

In vitro estimations of in vivo jet nebulizer efficiency using actual and simulated tidal breathing patterns.

In vivo aerosol delivery efficiency was estimated in vitro for two jet nebulizers using a breath monitor (Breathe!; Pari GmbH, Germany) and breath simulator (COMPAS; Pari GmbH) to reproduce subject tidal breathing patterns. The AeroEclipse (Trudell Medical International, Canada), a breath-actuated nebulizer, and the LC Star (Pari GmbH), a breath-enhanced nebulizer, were filled with levalbuterol HCl solution (Sepracor, USA) and operated with compressed O(2) at 8 lpm. Tidal breathing patterns of 20 adult subjects were digitally recorded with the Breathe! Breath Monitor. Subjects then breathed tidally from each nebulizer separately for 1 minute and to nebulizer dryness. Levalbuterol aerosol collected on filters placed between the nebulizer and mouth was chemically assayed to determine the inspired mass (IM), wasted mass (WM) and total emitted mass (TM). Measurements were repeated using the COMPAS Breath Simulator to simulate each subject's tidal breathing pattern. IM, WM, and TM measurements using actual versus simulated tidal breathing were highly comparable for each nebulizer, except the IM (p < 0.05) from LC Star measured at nebulizer dryness. Breath simulation was an inaccurate tool for estimating the time to nebulizer dryness as simulated measurements to nebulizer dryness took significantly longer than measurements preformed with actual tidal breathing (p < 0.001). While breath simulation provides an accurate in vitro tool for estimating in vivo aerosol delivery, it should not completely replace in vivo measurements until inherent limitations in simulator operation can be overcome to provide a more clinically realistic simulation.

Administration, Inhalation↗

Immunological and physical properties of allergen solutions. Effects of nebulization.

Lyophilised birch pollen allergen extracts, reconstituted with different diluents (H2O, saline, Albumin diluent (AD] were investigated to determine whether the allergen activity and quality of the extracts deteriorated by nebulization with different nebulizers (Pari, Wright, and Sandoz). Allergen activity was measured by IgG4 RAST inhibition technique and allergen quality was analysed by crossed immunoelectrophoresis (CIE). The distribution of particle sizes of aerosols of different allergen solutions was determined by a TSI Aerodynamic Particle Sizer. A significant difference (P less than 0.05) in allergen activity was found between the AD and H2O diluents before and after using a Sandoz nebulizer and a Wright nebulizer equipped with a small chamber. This suggested greater allergen activity in AD-diluted solutions, and the pattern was repeated with the other two nebulizers, but was not statistically significant. The samples diluted with saline showed no significant differences in quality after nebulization except for the impacted aerosol in which one of the precipitates was slightly diminished. In the AD-diluted sample one of the precipitates disappeared from the impacted aerosol and from the nebulization chamber after 2 min nebulization. To elucidate whether the extract proteins had been bound by albumin, samples were submitted to CIE with rabbit anti-human albumin in an intermediate gel. By this procedure one precipitate was transformed to a precipitate in the intermediate gel, indicating that one or more proteins in the extracts may associate with albumin. No significant difference in output was observed between the nebulizers. The particle size distribution curves for each diluent (saline, AD) were identical for the Wright nebulizer with 99% of the dry particles distributed within 0.5-2.0 microns.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗

Technetium-99m DTPA does not break down during ultrasound nebulization.

For several years aerosolized 99Tcm-DTPA has been used for studies of pulmonary permeability. Comparable results have been obtained regardless of the 99Tcm-DTPA having been nebulized in an ultrasound nebulizer or a jet nebulizer. It was therefore surprising when in a recent study it was observed that more than 90% of a commercially available 99Tcm-DTPA (Squibb) was dissociated into 99TcmO4- and DTPA during ultrasound nebulization. To verify this observation we performed chromatography of seven commercially available DTPA-labelling kits (including that of Squibb). Four different test preparations of each of the kits were analysed: (1) stock solution of 99Tcm-DTPA; (2) heated (80 degrees C) 99Tcm-DTPA; (3) 99Tcm-DTPA nebulized by a DeVilbiss ultrasound nebulizer; (4) 99Tcm-DTPA nebulized by a Varic ultrasound nebulizer. In no case were we able to demonstrate more than 1.0% reduced pertechnetate (99TcmO2) or more than 0.9% free 99TcmO4- after either heating or ultrasound nebulization. A maximum of 5.6% 99TcmO2 could be demonstrated in the stock solution if chromatography was done immediately after the preparation, but only 15 min later no more than 0.9% 99TcmO2 was present. We conclude that there is no essential chemical breakdown of 99Tcm-DTPA during ultrasound nebulization. Caution should be taken not to use the 99Tcm-DTPA until 15 min after its preparation.

Aerosols↗

Home-use nebulizers: a potential primary source of Burkholderia cepacia and other colistin-resistant, gram-negative bacteria in patients with cystic fibrosis.

Inhalation of aerosols contaminated with gram-negative bacteria generated from home-use nebulizers used by cystic fibrosis (CF) patients may be a primary route for bacterial colonization of the lung. Burkholderia cepacia was isolated from 3 of [corrected] 35 home-use nebulizers, and Stenotrophomonas maltophilia was isolated from 4 of 35 home-use nebulizers. Sputum cultures for two patients whose nebulizers were contaminated with B. cepacia did not yield the organism. However, DNA macrorestriction analysis by pulsed-field gel electrophoresis confirmed that one of two strains of B. cepacia recovered from the nebulizer of a third patient was also present in the sputum of that patient. Although Pseudomonas aeruginosa was isolated from 34 patients, none of the nebulizers were positive for the organism. Sixty-nine percent of nebulizers were contaminated, and up to 16 different environmental colistin-resistant, gram-negative species were identified. The heaviest contamination was found beneath the chamber atomizer. A questionnaire survey showed that the majority of patients (28 of 34) were receiving nebulized colistin and/or gentamicin. Patients who followed recommended instructions for good nebulizer hygienic practice and paid particular attention to drying had minimal or no contamination of their nebulizers.

Adult↗

Effect of dead volume on the efficiency and the cost to deliver medications in cystic fibrosis with four disposable nebulizers.

OBJECTIVES: To evaluate the factors that affect nebulizer efficiency and to compare the relative cost effectiveness of nebulized medications used in the treatment of cystic fibrosis (CF), delivered by four types of disposable jet nebulizers that are widely used in hospitals. DESIGN: The Hudson 1730 Updraft II, Baxter Misty-Neb, Marquest Whisper Jet (WJ), and Marquest Acorn II were evaluated in terms of respirable aerosol output (particles 5 microm or less), nebulizer dead (residual) volume (VD), and time for complete nebulization using saline, salbutamol and tobramycin at flows of 6 and 8 L/min. The respirable fraction (RF) was determined by laser diffraction, and drug output was calculated from the initial volume and concentration of the drug in the nebulizer minus the product of final drug concentration and the VD following nebulization. COST ANALYSIS: The expected pulmonary deposition (DE) was estimated, and incorporated with the material and labour costs to determine the cost effectiveness of each type of nebulizer. RESULTS: With a DE greater than two times that of the WJ at a cost of 2.4 times less, the Updraft II proved most efficient and cost effective of all the nebulizers evaluated in this study. CONCLUSIONS: The cost effectiveness of each nebulizer was determined by its efficiency, which in turn was predominantly related to its VD and RF at each flow. The efficiencies of these four devices were different and could not have been predicted from specifications provided by the respective manufacturers.

Administration, Inhalation↗

Nebulizer performance: AFLM study. Association Française de Lutte contre la Mucoviscidose.

This study was conducted by the AFLM order to determine the performance characteristics of 12 commercially available nebulizers (6 ultrasonic and 6 jet) used in the treatment of cystic fibrosis (CF). The nebulizers were connected to a circuit which simulated the ventilation of a CF child and CF adult, and were tested using three drug solutions: tobramycin (T), colistin (C), and amiloride (A). Nebulizer performance was evaluated according to the volume of drug solution delivered in 10 min during the simulated inspiratory phase (VI), drug granulometry (G%), drug concentration modification in the nebulizer reservoir (delta C), and percentage of efficiently aerosolized drug EA%). The ultrasonic devices delivered a significantly higher VI than the jet nebulizers (p < 0.0001) for all three study drug. Ventilation rate did not influence VI. Regarding granulometry, higher percentages of T and A were found to be contained in droplets ranging from 0.5 to 5.0 micron following ultrasonic nebulization. Drug concentration modifications were independent of the nebulizer used but were influenced by drug type; overconcentrations of T and A were observed (delta C = +10.5 +/- 18.6 and +13.4 +/- 8.9%, respectively). On average, the ultrasonic devices achieved a higher EA% than the jet nebulizers (17.3 +/- 6.7 and 9.7 +/- 9.6%, respectively). This study highlights the significant variability in performance of different nebulizer types and empahsizes the importance of accurately testing nebulizers prior to clinical use so that the most efficacious nebulizer/drug combinations may be prescribed.

Administration, Inhalation↗

The role of nebulized antibiotics in treating serious respiratory infections.

The administration of a nebulized antibiotic in serious respiratory tract infections ensures high antibiotic concentrations at the site of infection, minimising systemic concentrations and their resultant risk of toxicity. Nebulized antibiotics have been used for the treatment of chronic infection with Pseudomonas aeruginosa, particularly in cystic fibrosis, but with variable clinical efficacy. Antibiotic delivery by nebulization is greatly influenced by the product formulation and the nebulizer. Use of intravenous formulations via a nebulizer can lead to exposure to potentially irritant or toxic additives and inappropriate pH or osmolality ranges, whilst the choice of nebulizer can greatly influence the drug deposition in the airway. Tobramycin Nebulizer Solution (TNS) is the first specific formulation for nebulization in cystic fibrosis using a designated nebulizer. The potential extrapolation of nebulized antibiotic therapy to other serious respiratory infections, in particular bronchiectasis and ventilator-associated pneumonia, is explored in this review.

Administration, Inhalation↗

A comparison of pulmonary availability between Ventolin (albuterol) nebules and Ventolin (albuterol) Respirator Solution.

The two most common albuterol preparations used for nebulization are: (1) Ventolin (albuterol) respirator solution (Glaxo Canada Inc; Montreal, Canada) of which 2.5 mg (0.5 mL) is diluted with 2 mL of normal saline solution, and (2) the preservative-free, prediluted Ventolin (albuterol) Nebules PF (Glaxo) (2.5 mg/2.5 mL). The two preparations were compared using both a Hudson 1720 "T" up-draft Neb-U-Mist jet nebulizer and a Hudson 1730 "T" up-draft Neb-U-Mist II jet nebulizer (Hudson; Temecula, Calif), which were driven by a compressor (Pulmo-Aide; Devilbiss; Somerset, Pa) and by dry compressed air at 6 and 8 L/min. Particle size distribution was measured with a particle sizer (Malvern 2600; Malvern Instruments; Malvern, UK) and drug output for the nebulizer was calculated from the differences in predrug and postdrug volume and concentration. Drug availability was defined as the amount of drug carried in particles less than 5 microns in diameter. Drug availability was greater with the albuterol respiratory solution, due to the surface activity of the preservative benzalkonium chloride, for both nebulizers but particularly for the 1720. Differences in drug availability between nebulizers exceeded fourfold depending on the preparation, the nebulizer, and the nebulizing flow. These differences could not have been predicted from the manufacturer's specifications. The results suggest that prediction of drug availability must be based on measurements with the specific preparation and the specific nebulizer used.

Aerosols↗

In vitro characteristics of tobramycin aerosol from ultrasonic and jet nebulizers.

STUDY OBJECTIVE: To compare the in vitro performance of an ultrasonic nebulizer and a jet nebulizer in producing a respirable aerosol of tobramycin solution for injection. DESIGN: In vitro observational study DEVICES: Ultrasonic and jet nebulizers. INTERVENTION: Output was determined by measuring the difference in nebulizer weight before and after nebulizing 3 ml of tobramycin injection solution. Mass median aerodynamic diameter (MMAD) and respirable mass were determined by sampling tobramycin aerosol into a cascade impactor. MEASUREMENTS AND MAIN RESULTS: Mean (SD) output was 1.14 (0.09) ml/minute for the ultrasonic nebulizer and 0.64 (0.08) ml/minute (p<0.001) for the jet nebulizer. Mean MMAD for the jet nebulizer (2.31 [0.10] microm) was less than that of the ultrasonic nebulizer (2.81 [0.17] microm, p<0.001). The majority of tobramycin aerosol produced was in the respirable range for both the ultrasonic (65.1% [4.10%]) and jet (60.6% [0.73%], p=0.008) nebulizers. CONCLUSION: Despite small, clinically unimportant differences in aerosol size and respirable fraction, either device would be acceptable to administer tobramycin injection solution.

Aerosols↗