A Retrospective Comparison of the Effectiveness of Buprenorphine Versus Baclofen for Acute Opioid Withdrawal.

Background: A significant impediment to opioid cessation or dose reduction is mitigating withdrawal severity that has been shown to affect the course of opioid dependence. Current guidelines recommend the use of buprenorphine and methadone over alpha-2 adrenergic agonists. Baclofen, a GABA-B agonist, has promising results as an adjunct agent for opioid withdrawal but has not been compared to buprenorphine. This study compared the ability of buprenorphine and baclofen to mitigate acute opioid withdrawal. Methods: This was a single-center, retrospective chart review of 63 patients with diagnosed opioid use disorder that received scheduled buprenorphine or baclofen for 3 days, in addition to as-needed medications during 2 distinct time periods (pre-2017 and 2017-2020). Patients were admitted to the inpatient detoxification unit at Gateway Community Services in Jacksonville, FL. Results: The results showed that patients achieving detoxification success were 11.2 times more likely to be exposed to baclofen than buprenorphine (95% CI 3.32 - 37.83, P < .001). Completion of detoxification protocol (baclofen 63.2% vs buprenorphine 72%, P = .649) and incidence of orthostatic hypotension (15.8% versus 0%, P = .073) were not significantly different between the 2 groups. Conclusion: Patients treated with baclofen had a lower frequency of secondary medication use for acute opioid withdrawal than patients treated with buprenorphine. This raises an interesting question of whether baclofen is comparable to buprenorphine for treating opioid withdrawal. A prospective, randomized, controlled trial in a larger patient population is warranted to determine this difference.

Child Psychiatry Consultation Clinic for Pediatricians: Long-Term Outcomes.

There is an urgent need for new clinical models to improve access to child mental health care. Pediatricians are tasked to care for youth with mild to moderate mental health problems, but require additional training. This article describes an outpatient child psychiatry consultation clinic (CPC) designed to empower pediatricians to care for youth with depression, anxiety, and attention deficit/hyperactivity disorder. Over a 2-year period, 40 primary care physicians (PCPs) referred 159 patients to the CPC. The most common primary diagnoses of patients seen for consultation were generalized anxiety disorder (35%), major depressive disorder (24%), and attention deficit/hyperactivity disorder (20%). Most patients (89%) had at least 2 psychiatric diagnoses. Nearly four fifths (79%) of these patients successfully returned to their PCP for ongoing care. PCPs reported that the CPC enhanced their skills and improved access to mental health care. Similar models are needed to facilitate early intervention for the millions of youth with mental health problems.

Post-Parkland Shooting: Development and Assessment of Experiential Training in Adolescent Depression and Post-Traumatic Stress Disorder for Primary Care Providers.

Primary care pediatric providers (PCPs) could facilitate early intervention for youth impacted by trauma, yet lack appropriate training. Experiential training for PCPs following a school shooting helped improve PCP confidence and practices in caring for youth with depression and post-traumatic stress disorder.

Delivery of Epinephrine in the Vapor Phase for the Treatment of Croup.

OBJECTIVES: The Vapotherm system delivers high humidity to the airway of patients by using semipermeable tubules where heated liquid water is in contact with air. The humidified air is conducted to the patient via a heated tube. Preliminary clinical observations in infants with croup suggested that epinephrine added to the water supplying the humidity was delivered successfully in the vapor phase. The purpose of this study was to evaluate the efficiency of the delivery of epinephrine in the vapor phase and to develop the feasibility criteria for a clinical pilot study. DESIGN: Thirty milligrams of epinephrine in a 1-L bag of sterile water was used as the humidification source for a Vapotherm 2000i. The output of the heated circuit was condensed and collected into a small Erlenmeyer flask via a metal coil while the whole collection system was submerged in an ice slurry to maintain the outflow temperature from the flask between 0°C and 2°C. The in vitro system was tested at 40°C with flows of 5, 10, and 15 L/min and L-epinephrine concentrations of 15, 30, and 60 mg/L. Each test was duplicated at each of the six conditions. SETTING: Academic children's hospital research laboratory. PATIENTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The system recovered more than 90% of the water vapor from the fully saturated air at 40°C. The epinephrine concentration recovery quantified by ultraviolet-visible spectrophotometry was 23.9% (27.5-20.4%) (mean and range) of the initial concentration. At flows of 5, 10, and 15 L/min, the delivery of epinephrine would be 1.8, 3.6, and 4.2 µg/min, respectively, which is in the therapeutic range used for parenteral infusion in young children. CONCLUSIONS: The Vapotherm system can be used to deliver epinephrine in pharmacological doses to the respiratory system as a vapor and thus as an alternative to droplets by conventional nebulization.

Developing alternative delivery systems for methacholine challenge tests.

BACKGROUND: The two American Thoracic Society recommended aerosol delivery devices for methacholine challenge testing are both obsolete and often very difficult to acquire, leading to the test being done with a number of nonstandardized nebulizers. Of the two recommended devices, one is the English Wright nebulizer used in the 2-min tidal breathing method, and the other is the DeVilbiss 646 nebulizer used in the five-breath dosimeter method. The purpose of this study was to evaluate the in vitro performance of potential alternative devices that would be economically viable and would minimize environmental contamination. One device was the disposable breath-actuated AeroEclipse(®) II BAN as a potential delivery system for the 2-min tidal breathing, and the second was the automated system by VIASYS as an alternative to either the 2-min tidal breathing or the five-breath dosimeter method. METHODS: A breath simulator mimicked an adult or small child breathing pattern, and a slow inhalation for the five-breath method was generated by a spirometry calibration syringe. Methacholine (Provocholine™) was eluted from filters at the "mouth" and assayed by high-pressure liquid chromatography. RESULTS: In 12 sec, the AeroEclipse II BAN would be expected to have a pulmonary deposition equivalent to the 2-min tidal breathing with the English Wright, whereas the VIASYS system would take approximately 40 sec for the equivalent delivery. The per-breath delivery of the VIASYS and the DeVilbiss 646 was approximately the same, whereas one breath from the AeroEclipse II BAN was the equivalent of five from the DeVilbiss 646. CONCLUSIONS: These data will allow for planning in vivo studies to develop methacholine challenge protocols using modern aerosol delivery systems.

Aerosolized liposomal Amphotericin B: a potential prophylaxis of invasive pulmonary aspergillosis in immunocompromised patients.

BACKGROUND: Aerosolized liposomal Amphotericin B may reduce the incidence of invasive pulmonary Aspergillosis in adults with chemotherapy-induced prolonged neutropenia with less nephrotoxicity. The breath-actuated AeroEclipse® BAN nebulizer is very efficient and minimizes environmental drug contamination since no aerosol is produced, unless the patient is inspiring through the device. Our aim is to develop an appropriate delivery system suitable for children that does not disrupt the liposomes due to the shear forces in nebulization. METHODS: This is an in vitro experimental study in vitro. Six ml of 4 mg/ml liposomal Amphotericin B solution (AmBisome®; Astellas Pharma Inc., Markham, Ontario, CA) was nebulized with the breath-actuated nebulizer (AeroEclipse®; Trudell Medical International, Canada) and captured by the glass liquid impinger. Sodium dodecyl sulfate was used as detergent to disrupt the liposomes in control samples. Gel filtration, electron microscopy, and high performance liquid chromatography (HPLC) were used to compare the size and shape of the liposomes, and amount of the drug before and after nebulization. The aerosol particle size was obtained by the laser diffraction. RESULTS: After nebulization, 97.5% of amphotericin B was captured by the liquid impinger and detected by HPLC. Gel filtration and electron microscopy demonstrated that the drug remained in its liposomal configuration after nebulization. The mass median diameter (MMD) was 3.7 µm and 66% of aerosol particles were less than 5 µm in diameter. CONCLUSIONS: We demonstrated that liposomal Amphotericin B can be nebulized successfully without disrupting the liposomes and minimize drug loss by using the breath-actuated nebulizer.

Efficient gene delivery to pig airway epithelia and submucosal glands using helper-dependent adenoviral vectors.

Airway gene delivery is a promising strategy to treat patients with life-threatening lung diseases such as cystic fibrosis (CF). However, this strategy has to be evaluated in large animal preclinical studies in order to translate it to human applications. Because of anatomic and physiological similarities between the human and pig lungs, we utilized pig as a large animal model to examine the safety and efficiency of airway gene delivery with helper-dependent adenoviral vectors. Helper-dependent vectors carrying human CFTR or reporter gene LacZ were aerosolized intratracheally into pigs under bronchoscopic guidance. We found that the LacZ reporter and hCFTR transgene products were efficiently expressed in lung airway epithelial cells. The transgene vectors with this delivery can also reach to submucosal glands. Moreover, the hCFTR transgene protein localized to the apical membrane of both ciliated and nonciliated epithelial cells, mirroring the location of wild-type CF transmembrane conductance regulator (CFTR). Aerosol delivery procedure was well tolerated by pigs without showing systemic toxicity based on the limited number of pigs tested. These results provide important insights into developing clinical strategies for human CF lung gene therapy.Molecular Therapy-Nucleic Acids (2013) 2, e127; doi:10.1038/mtna.2013.55; published online 8 October 2013.

Respiratory system deposition with a novel aerosol delivery system in spontaneously breathing healthy adults.

BACKGROUND: Intravenous magnesium sulfate (MgSO(4)) in children and adults with refractory acute asthma is effective, but therapy may be limited by systemic hypotension that might be avoided with the aerosol route. Inhaled MgSO(4) has a relatively high dose (volume) requirement. This, plus the use of inefficient delivery systems, may explain the lack of efficacy of inhaled MgSO(4) in some studies. An in vitro study suggested that the AeroNeb Go with the Idehaler Pocket and a face mask would deliver 16 mg/min of MgSO(4) to the respiratory system in older children, and approximately a fifth for toddlers, but no in vivo data exist. METHODS: Saline mixed with a radiolabel was used as a proxy for the 100 mg/mL MgSO(4) solution. In 5 adult males the rate of deposition was measured using nuclear medicine techniques. The radiolabel deposition below the vocal cords was converted to the rate of deposition of MgSO(4) and compared to the results from an in vitro model using adult respiratory patterns. RESULTS: The mean ± SD rate of deposition was 12.6 ± 1.9 mg/min. The reasons for this lower deposition, compared to the in vitro estimate, was most likely the exhalation of anatomical dead space aerosol, which would have been captured on the inspiratory filter in vitro. CONCLUSIONS: These in vivo data confirm the deposition data predicted in the in vitro study, although caution should be used in extrapolating the results to children. This device appears suitable for the clinical trial of inhaled MgSO(4) in children and adults with refractory asthma.

Modeling breath-enhanced jet nebulizers to estimate pulmonary drug deposition.

BACKGROUND: Predictable delivery of aerosol medication for a given patient and drug-device combination is crucial, both for therapeutic effect and to avoid toxicity. The gold standard for measuring pulmonary drug deposition (PDD) is gamma scintigraphy. However, these techniques expose patients to radiation, are complicated, and are relevant for only one patient and drug-device combination, making them less available. Alternatively, in vitro experiments have been used as a surrogate to estimate in vivo performance, but this is time-consuming and has few "in vitro to in vivo" correlations for therapeutics delivered by inhalation. An alternative method for determining inhaled mass and PDD is proposed by deriving and validating a mathematical model, for the individual breathing patterns of normal subjects and drug-device operating parameters. This model was evaluated for patients with cystic fibrosis (CF). METHODS: This study is comprised of three stages: mathematical model derivation, in vitro testing, and in vivo validation. The model was derived from an idealized patient's respiration cycle and the steady-state operating characteristics of a drug-device combination. The model was tested under in vitro dynamic conditions that varied tidal volume, inspiration-to-expiration time, and breaths per minute. This approach was then extended to incorporate additional physiological parameters (dead space, aerodynamic particle size distribution) and validated against in vivo nuclear medicine data in predicting PDD in both normal subjects and those with CF. RESULTS: The model shows strong agreement with in vitro testing. In vivo testing with normal subjects yielded good agreement, but less agreement for patients with chronic obstructive lung disease and bronchiectasis from CF. CONCLUSIONS: The mathematical model was successful in accommodating a wide range of breathing patterns and drug-device combinations. Furthermore, the model has demonstrated its effectiveness in predicting the amount of aerosol delivered to "normal" subjects. However, challenges remain in predicting deposition in obstructive lung disease.

A comparison of amount and speed of deposition between the PARI LC STAR® jet nebulizer and an investigational eFlow® nebulizer.

BACKGROUND: The potency and physical properties of many of the drugs used in the treatment of cystic fibrosis necessitates the use of nebulization, a relatively time-consuming pulmonary delivery method. Newer, faster, and more efficient delivery systems are being proposed. The purposes of this study was to compare the length of time it took to deliver the equivalent of normal saline nebulized for 10 min in a PARI LC STAR(®) nebulizer to that of an investigational PARI eFlow(®). METHODS: Six normal adults inhaled a 4-mL (36-mg) charge volume of saline from the LC STAR(®) or a 2.5-mL (22.5-mg) charge volume from the investigational eFlow(®). The saline was mixed with (99m)Tc-DTPA to allow two-dimensional imaging. The inhalation was preceded by a xenon equilibration scan to allow more accurate separation of deposition into central and peripheral lung regions. RESULTS: The investigational eFlow(®) delivered 8.6 ± 1.0 mg, approximately 90% of the lung dose compared to the LC STAR(®), 9.6 ± 1.0 mg, but did in less than half the time (p < 0.02 for both). There were no differences in central versus peripheral distribution for either device. CONCLUSIONS: In conclusion the investigational eFlow(®) was both faster and more efficient than the LC STAR(®).

Higher tobramycin concentration and vibrating mesh technology can shorten antibiotic treatment time in cystic fibrosis.

Poor adherence to recommended therapy in cystic fibrosis (CF) is often because of the time demands of therapy. Tobramycin (TOBI®, 300 mg at 60 mg/ml) inhaled from the PARI LC PLUS® nebulizer requires about 20 min. This study determined if equivalent levels of pulmonary deposition could be achieved in shorter time using 1.5 ml of 100 mg/ml tobramycin solution delivered by an investigational eFlow® nebulizer. Sixteen males with stable CF, 8 children and 8 adults, and an FEV(1) > 45% predicted inhaled both preparations on two occasions with (99m) Tc-DTPA added to the tobramycin. Blood samples were taken for quantification of tobramycin in the serum. The PARI LC PLUS® delivered 45.4 (39.3-51.6), mean and 95% CI, mg to the lungs in 17.0 ± 2.5 min (mean ± SD) with serum levels of 1,089 ± 388 µg/L. The investigational eFlow® delivered 46.3(40.3-51.7) mg in 4.0 ± 1.0 min with blood levels of 909 ± 458 µg/L. Only the time of delivery was significantly different with P < 0.0001 (paired t-test). Tolerability of the treatment was comparable for both inhalation regimes, but the shorter treatment was preferred by all patients. These results demonstrate the possibility of delivering equivalent levels of tobramycin much faster into the lungs of CF patients when using eFlow®, a very efficient electronic nebulizer.

Testing of nebulizers for delivering magnesium sulfate to pediatric asthma patients in the emergency department.

BACKGROUND: As the use of intravenous magnesium sulfate (MgSO(4)) for the treatment of refractory asthma is becoming more common, the incidence of MgSO(4)-related systemic hypotension is also rising. One option is to deliver MgSO(4) via aerosol, but compared to most inhaled medications, which are active in the microgram dose range, the MgSO(4) dose requirement is in the milligram range. This, along with inefficient aerosol delivery systems, may be the reason that some studies have found lack of efficacy with aerosol MgSO(4). In preparation for a multicenter study of inhaled MgSO(4) in asthmatic children 2-17 years old, we conducted an in vitro study to choose the best MgSO(4) nebulizer system that would be effective over the entire age range. METHODS: We tested the Pari LC Star jet nebulizer, Omron MicroAir vibrating-mesh nebulizer, and the Aeroneb Go vibrating-mesh nebulizer with the Idehaler valve-less holding chamber. Aerosol delivery was via face mask. RESULTS: The Pari LC Star had an appropriate particle size distribution but a very slow aerosol output rate. The Omron MicroAir had an even slower output rate and a larger particle size distribution, which would be inappropriate for smaller children. In vitro lung deposition with the Aeroneb Go with Idehaler was 16.0 ± 0.4 mg/min in older children and approximately a fifth of that in toddlers. CONCLUSIONS: The Aeroneb Go with Idehaler was chosen for the multicenter clinical study.

Rapid pulmonary delivery of inhaled tobramycin for Pseudomonas infection in cystic fibrosis: a pilot project.

BACKGROUND: Patients with cystic fibrosis spend as much 30 min a day inhaling tobramycin. Could a new rapid system deposit the equivalent amount of tobramycin faster? METHODS: Six healthy adult males inhaled 5 ml (300 mg) of tobramycin from a breath enhanced nebulizer and either 125 mg (n = 3) or 150 mg (n = 3) from a vibrating membrane system with a large or small aerosol mixing chamber respectively. A radiolabel was added to the solution and shown to "track" with the tobramycin. Imaging was done with a dual headed gamma camera. Because the radiolabel will be cleared by mucociliary action during administration, algorithms were developed to allow the comparison of a slower system to a faster one. RESULTS: Both formulations were well tolerated. The lung deposition was 16.6 +/- 3.2% (mean +/- SD) of the charge dose delivered in 10.9 +/- 1.0 min for the breath enhanced nebulizer versus 32.0 +/- 5.1% delivered in 2.5 +/- 0.4 min from the vibrating membrane system. The absolute pulmonary delivery of tobramycin was 49.9 +/- 9.6 versus 43.9 +/- 4.8 mg for the two systems respectively, differences that were statistically significant (pair t-test) but unlikely to be clinically significant. There was a similar deposition of tobramycin for the 125 and 150 mg dose. CONCLUSIONS: It is possible to deliver an equivalent amount of tobramycin in a shorter period of time with the new vibrating membrane system and a more concentrated formulation. These data will allow the design of a comparison in patients with CF.

The challenges of quantitative measurement of lung deposition using 99mTc-DTPA from delivery systems with very different delivery times.

In quantifying aerosol delivery, the drug is often mixed with a radiolabel such as (99m)Tc-DTPA whose deposition is used as a proxy for the drug. (99m)Tc-DTPA deposited in the lung is cleared by a combination of absorption into the pulmonary circulation and mucociliary clearance. If administration is not instantaneous, the image will not include that clearance during administration, a problem raised if comparing devices with different administration times. However, if rates of clearance are measured, it will be possible to "correct" the initial image for the clearance that occurred during administration and before counting. Five adult males inhaled a 5-mL solution containing (99m)Tc-DTPA from a breath enhanced jet nebulizer (LC Plus)over the course of 10 min and a 1.25-mL solution from a vibrating membrane device (eFlow), which was delivered in 2.5 min. Quality assurance was the radioactivity count balance (RCB) defined as the difference in the total radioactivity pre-nebulization less post, divided by pre, and expressed as a percentage. Attenuation calculations used a (57)Co flood source (Macey and Marshall). The "correction" for the clearance of (99m)Tc-DTPA was 0.91 +/- 0.04 (mean +/- SD) for the LC Plus) and 0.96 +/- 0.02 for the eFlow). RCB was -0.6 +/- 3.5% for the LC Plus and -4.7 +/- 6.4% for the eFlow, implying acceptable accuracy. For the LC Plus, lung deposition was 15.9(13.4, 18.4)% (mean and 95% CI) of the charge dose, and for the eFlow it was 32.0(29.0, 35.0)%. This technique gave an acceptable level of accuracy for quantitative planar imaging and allowed the comparison of delivery from devices with very different rates of delivery.

Calculating expected lung deposition of aerosolized administration of AAV vector in human clinical studies.

BACKGROUND: Cystic fibrosis is an autosomal recessive disease affecting approximately 1 in 2500 live births. Introducing the cDNA that codes for normal cystic fibrosis transmembrane conductance regulator (CFTR) to the small airways of the lung could result in restoring the CFTR function. A number of vectors for lung gene therapy have been tried and adeno-associated virus (AAV) vectors offer promise. The vector is delivered to the lung using a breath-actuated jet nebulizer. The purpose of this project was to determine the aerosolized AAV (tgAAVCF) particle size distribution (PSD) in order to calculate target doses for lung delivery. METHODS: A tgAAVCF solution was nebulized using the Pari LC Plus (n = 3), and the PSD was determined by coupling laser diffraction and inertial impaction (NGI) techniques. The NGI allowed for quantification of the tgAAVCF at each stage of impaction, ensuring that rAAV-CFTR vector is present and not empty particles. Applying the results to mathematical algorithms allowed for the calculation of expected pulmonary deposition. RESULTS: The mass median diameter (MMD) for the tgAAVCF was 2.78 +/- 0.43 microm. If the system works ideally and the patient only receives aerosol on inspiration, the patient would receive 47 +/- 0% of the initial dose placed in the nebulizer, with 72 +/- 0.73% of this being deposited beyond the vocal cords. CONCLUSIONS: This technology for categorizing the pulmonary delivery system for lung gene therapy vectors can be adapted for advanced aerosol delivery systems or other vectors.

Comparison of three valved holding chambers for the delivery of fluticasone propionate-HFA to an infant face model.

The purpose of this study was to compare three valved holding chambers (VHC) with facemasks attached. One VHC (AeroChamber Max[TM] with medium mask) was made with materials that dissipate surface electrostatic charge, and the others (OptiChamber Advantage and ProChamber[TM] with pediatric facemask) were made from non-conducting materials. The OptiChamber Advantage and ProChamber VHCs were each washed with an ionic detergent and drip dried before testing to minimize surface electrostatic charge. The AeroChamber Max VHCs were tested "out of the package" and also after wash, rinse, and drying. An infant face model incorporating an electrostatic filter in the oral cavity was connected to a breath simulator using a standard waveform for a small child. The fit of each VHC with facemask was demonstrated by agreement of inspiratory flow measurements between a pneumotachograph connected to the system with those set on the simulator. An HFA-fluticasone propionate metered dose inhaler (MDI; 125 microg/dose) was inserted into the VHC, two actuations were delivered, and the filters were subsequently assayed using high-pressure liquid chromatography (HPLC). Testing and sample assay order was randomized, and HPLC assays were undertaken blinded. Drug delivery efficiency expressed as a percentage of the total dose of fluticasone propionate (250 microg) for the AeroChamber Max VHC "out-of-the-package" was 22.0(0.7)% (mean [99% CI]) and 21.2(1.5)% when pre-washed/rinsed. Results for the pre-washed ProChamber and OptiChamber Advantage VHCs were 10.2(0.55)% and 8.8(1.9)%, respectively. The more efficient delivery of medication via VHCs made from electrostatic charge dissipative materials should be considered when choosing doses for small children.

Nebulized therapies for childhood pulmonary hypertension: an in vitro model.

OBJECTIVES: Sildenafil, tezosentan, and prostacyclin reduce pulmonary vascular pressures in pulmonary hypertension, but have potential to vasodilate the systemic circulation. Nebulized vasodilators allow targeted drug delivery, high local drug concentrations, less systemic hypotension, and better matching of the lung's ventilation and perfusion. We aimed to estimate pulmonary deposition of these drugs from commonly employed nebulizers using in vitro techniques and to create a mathematical model to predict inspired mass of aerosol. DESIGN: Lung deposition was estimated by characterization of drug output and particle size distribution (PSD) of nebulizers using helium-neon laser diffraction techniques. A mathematical model for each device was created to estimate pulmonary deposition using patients' breathing patterns and was verified with a mechanical-breathing model. RESULTS: Total output and PSD were similar for the Hudson Updraft II and Whisperjet nebulizers, consisting of half the nebulizer's charge, with (1/4) of particles < or = 5 microm, in the respirable fraction (RF). Drug output increased with inspiratory flow for the Pari LC Star. Differences were noted in device performance, depending on the drug tested. Estimated pulmonary deposition (mean, 95% CI) was 8.1 (7.2, 9.0)% of the initial drug charge for the Hudson Updraft II, 6.4 (5.8, 7.0)% for the Whisperjet, and 33.0 (28.3, 37.9)% for the Pari LC Star. A mechanical model was consistent with our mathematical model. CONCLUSIONS: All drugs could be nebulized, but expected pulmonary deposition varied depending on the nebulizer and drug.

How many infective viral particles are necessary for successful mass measles immunization by aerosol?

OBJECTIVES: This study characterized the performance of the "Classical Mexican Device", which immunized 4 million children against measles, demonstrating the efficacy of aerosol vaccination. METHODS: Using plaque-forming units to quantify virus, the particle size distribution (Next Generation Pharmaceutical Impactor) and rate of output coupled with age specific patterns of breathing allowed the calculation of expected pulmonary deposition. RESULTS: The estimated immunization dose for infants was 30 pfu's, for small children 50, and for older children and adolescents it was 130 and 225, respectively. CONCLUSIONS: These performance characteristics can be used to develop newer battery operable devices that are licensable.

Use of the next generation pharmaceutical impactor for particle size distribution measurements of live viral aerosol vaccines.

Aerosol administration of live measles vaccine virus has proven to be extremely efficacious in field trials using an industrial compressor coupled to a disposable nebulizer (IPI). To develop a new system for administration, it is necessary to characterize the operating characteristics of the old system. There are no standardized techniques for measuring particle size of live biological agents. This study evaluated the Next Generation Pharmaceutical Impactor's (NGI) ability to particle size wet aerosols in an effort to measure the particle size distribution of live measles vaccine from the IPI nebulizer. As a control albuterol was aerosolized using a Pari LC Star, since the soluble albuterol is evenly distributed throughout the droplets and laser diffraction measurements should agree with those from the NGI, as long as the NGI is cooled to prevent heat transfer to the aerosol. Albuterol was also used as a control for the IPI using quantitative ultraviolet spectrophotometry. There was close agreement in MMD (mean +/- 95% CI) for the LC Star, measured by laser diffraction (3.24 +/- 0.06 microm) and the NGI (2.93 +/- 0.22 microm) and the IPI (4.26 +/- 0.17 and 4.26 +/- 0.24 microm, respectively). For the measles vaccine assayed for plaque forming units, there were significant differences between the NGI MMD (6.14 +/- 0.39 microm) compared to laser diffraction (4.95 +/- 0.16 microm) indicating that the vaccine is not evenly distributed among the droplets of various sizes. This is likely clumping of the virus due to gelatin in the formulation. These data indicate that the NGI is capable of particle sizing live biological agents.