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Operating Characteristics of 18 Different Continuous-Flow Jet Nebulizers With Beclomethasone Dipropionate Liposome Aerosol

1994; Elsevier BV; Volume: 105; Issue: 1 Linguagem: Inglês

10.1378/chest.105.1.106

1931-3543

John C. Waldrep, Keyvan Keyhani, Melanie Black, Vernon Knight,

Occupational exposure and asthma

A study of 18 different commercially available continuous-flow, jet nebulizers was performed with a standard liposomal formulation of beclomethasone dipropionate (Bec-DP) prepared with dilauroyl phosphatidylcholine (Bec-DLPC). The analysis compared the total Bec-DP output from aqueous suspensions of Bec-DLPC containing an initial starting reservoir concentration of 0.5 mg/mL Aerosols from each nebulizer tested were characterized by the mass median aerodynamic diameter, geometric standard deviation, drug output, and the predicted percentage regional deposition of inhaled Bec-DLPC liposomes within the human respiratory tract These data can provide a basis for the selection of commercially available jet nebulizers for use with glucocorticoid liposome aerosols for treatment of asthma and other inflammatory lung diseases. A study of 18 different commercially available continuous-flow, jet nebulizers was performed with a standard liposomal formulation of beclomethasone dipropionate (Bec-DP) prepared with dilauroyl phosphatidylcholine (Bec-DLPC). The analysis compared the total Bec-DP output from aqueous suspensions of Bec-DLPC containing an initial starting reservoir concentration of 0.5 mg/mL Aerosols from each nebulizer tested were characterized by the mass median aerodynamic diameter, geometric standard deviation, drug output, and the predicted percentage regional deposition of inhaled Bec-DLPC liposomes within the human respiratory tract These data can provide a basis for the selection of commercially available jet nebulizers for use with glucocorticoid liposome aerosols for treatment of asthma and other inflammatory lung diseases. actual cubic feet per minute beclomethasone dipropionate-dilauroyl phosphatidylcholine beclomethasone dipropionate dilauroyl phosphatidylcholine glucocorticoid geometric standard deviation nigh-performance liquid chromatography mass median aerodynamic diameter phosphatidylcholine Localized aerosol delivery of drugs to the respiratory tract is becoming an increasingly important and effective therapeutic method for treating a variety of pulmonary disorders. In this regard, several different devices have been used, including continuous-flow, jet nebulizers.1Clay M.M. Pavia D. Newman S.P. Clarke S.W. Factors influencing the size distribution of aerosols from jet nebulizers.Thorax. 1983; 38: 755-759Crossref PubMed Scopus (154) Google Scholar, 2Newman S.P. Pellow P.G.D. Clarke S.W. Droplet size distributions of nebulized aerosols for inhalation therapy.Clin Phys Physiol Meas. 1986; 7: 139-146Crossref PubMed Scopus (75) Google Scholar, 3Newman S.P. Pellow P.G.D. Clarke S.W. In vitro comparison of devils jet and ultrasonic nebulizers.Chest. 1987; 6: 991-994Crossref Scopus (46) Google Scholar, 4O'Doherty M.J. Page C. Bradbeer C. Thomas S. Barlow D. Nunan T.O. et al.Differences in relative efficiency of nebulizers for pentamidine administration.Lancet. 1988; 2: 1283-1286Abstract PubMed Scopus (55) Google Scholar To date, jet nebulizers have been used predominantly to administer aqueous preparations of soluble drugs such as ribavirin, pentamidine, bronchodilators, mucolytic agents, and antibiotics.5Knight V. Yu C.P. Gilbert B.E. Divine G.W. Estimating dose of ribavirin aerosol according to age and other variables.J Infect Dis. 1988; 158: 443-448Crossref PubMed Scopus (33) Google Scholar, 6Montgomery A.B. Debs R.J. Luce J.M. Corkery K.J. Turner T. Brunette E.N. et al.Selective delivery of pentamidine to the lung by aerosol.Am Rev Resp Dis. 1988; 137: 477-478Crossref PubMed Scopus (62) Google Scholar, 7Hodson M. Penketh A. Batten J.C. Aerosol carbenicillin and gentamicin treatment of Pseudomonas aeruginosa infection in patients with cystic fibrosis.Lancet. 1981; 2: 1137-1139Abstract PubMed Scopus (250) Google Scholar, 8Clarke S.W. Newman S.P. Therapeutic aerosols: II. Drugs available by the inhaled route.Thorax. 1984; 39: 1-7Crossref PubMed Scopus (40) Google Scholar, 9Rao S. Wilson D.B. Brooks R.C. Sproule B.J. Acute effects of nebulization of N-acetyl-cysteine on pulmonary mechanics and gas exchange.Am Rev Respir Dis. 1970; 102: 17-22PubMed Google Scholar More recently, liposomes have been used to formulate. aqueous solutions of water-insoluble, lipophilic drugs like enviroxime, cyclosporine, or amphotericin B for use with jet nebulizers.10Gilbert B.E. Six H.R. Wilson S.Z. Wyde P.R. Knight V. Small particle aerosols of enviroxime-containing liposomes.Antiviral Res. 1988; 9: 355-365Crossref PubMed Scopus (57) Google Scholar, 11Gilbert B.E. Wyde P.R. Wilson S.Z. Aerosolized liposomal amphotericin B for treatment of pulmonary and systemic Cryptococcus neoformans infections in mice.Antimicrob Agents Chemother. 1992; 36: 1466-1471Crossref PubMed Scopus (33) Google Scholar, 12Waldrep JC, Scherer PW, Keyhani K, Knight V. Cyclosporin A liposome aerosol: particle size and calculated respiratory deposition. Int J Pharmaceut (in press)Google Scholar In this study, we report liposomal formulation of the topically active glucocorticoid (GC), beclomethasone dipropionate (Bec-DP), with dilauroyl phosphatidylcholine (DLPC) for aerosol delivery to the lung using jet nebulizers. Comparative analysis of the many different jet nebulizers for such use in other systems has demonstrated a range of performance characteristics.1Clay M.M. Pavia D. Newman S.P. Clarke S.W. Factors influencing the size distribution of aerosols from jet nebulizers.Thorax. 1983; 38: 755-759Crossref PubMed Scopus (154) Google Scholar, 2Newman S.P. Pellow P.G.D. Clarke S.W. Droplet size distributions of nebulized aerosols for inhalation therapy.Clin Phys Physiol Meas. 1986; 7: 139-146Crossref PubMed Scopus (75) Google Scholar, 3Newman S.P. Pellow P.G.D. Clarke S.W. In vitro comparison of devils jet and ultrasonic nebulizers.Chest. 1987; 6: 991-994Crossref Scopus (46) Google Scholar, 4O'Doherty M.J. Page C. Bradbeer C. Thomas S. Barlow D. Nunan T.O. et al.Differences in relative efficiency of nebulizers for pentamidine administration.Lancet. 1988; 2: 1283-1286Abstract PubMed Scopus (55) Google Scholar In the present report, we have compared the properties of aerosols of beclomethasone dipropionate-dilauroyl phosphatidylcholine (Bec-DLPC) liposomes generated by 18 different commercially available jet nebulizers. Data are presented for each nebulizer with measurements of mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD), and the predicted percentage of regional deposition of Bec-DLPC liposomes within the human respiratory tract. Recently, we administered Bec-DLPC liposome aerosol to nine normal volunteers with no untoward clinical or laboratory effects (unpublished data, this laboratory). We thus believe that the information provided below will make possible studies by others on this new approach to the aerosol administration of GCs. Beclomethasone dipropionate (Orion Pharmaceutica, Espoo, Finland) was combined with DLPC (Avanti Polar Lipids, Inc, Alabaster, Ala) in a ratio of 1:25 by weight (1:21 molar ratio). Typically, 15 mg of Bec-DP was mixed with stirring with 375 mg of DLPC at 37°C in 10 ml of tertiary butanol. The mixture was pipetted into glass vials, rapidly frozen in an acetone-dry ice slurry, and lyophilized overnight to remove t-butanol.12Waldrep JC, Scherer PW, Keyhani K, Knight V. Cyclosporin A liposome aerosol: particle size and calculated respiratory deposition. Int J Pharmaceut (in press)Google Scholar Multilamellar liposomes were produced by adding ultrapure water, prewarmed to 37°C, which is well above the DLPC phase transition temperature of −2°C, to deliver a final Bec-DP concentration of 0.5 mg/ml. To produce liposomes, the mixture was swelled for 30 min at 37°C with mixing on a rocker platform. The liposome preparations were examined microscopically to ensure that they were free of lipid aggregates and microscopic drug crystals. The Bec-DLPC liposome drug encapsulation efficiency was determined by high-performance liquid chromatography (HPLC) analysis of the filtrate obtained using Centrifree micropartition system, Amicon, Beverly, Mass.13Taniguchi K. Yamazawa N. Itakura K. Morisaki K. Hayashi S. Partition characteristics of anti-inflammatory steroids in liposomal ophthalmic preparations.Chem Pharm Bull. 1987; 35: 1214-1222Crossref PubMed Scopus (26) Google Scholar Ninetyseven to 99 percent of the Bec-DP remained associated with the DLPC while only 1 to 3 percent passed the filter in the soluble phase. The Bec-DLPC liposomes in water (initial Bec concentration 0.5 mg/ml) were added to the jet nebulizer reservoir according to the maximum volume (Table 1). The nebulizers were selected at random and operated using dry compressed air at flow rates prescribed by the manufacturer's instructions or at 7.5 to 8 L/min (Table 1).Aerosol sampling was begun after 5 min of operation of the nebulizer to equilibrate the system and continued for 2.5 min. This sampling interval provided sufficient drug levels for accurate biochemical analysis. The Bec-DLPC liposomes were collected in a nonviable ambient particle sizing sampler (actual 1 cubic feet per minute [ACFM], Andersen Instruments, Inc, Atlanta).12Waldrep JC, Scherer PW, Keyhani K, Knight V. Cyclosporin A liposome aerosol: particle size and calculated respiratory deposition. Int J Pharmaceut (in press)Google Scholar,14Andersen A.A. New sampler for the collection, sizing, and enumeration of viable airborne particles.J Bacteriol. 1958; 76: 471-484Crossref PubMed Scopus (941) Google Scholar, 15Nilsson G. Brunzell A. Estimation of particle size in medical aerosols with a cascade impactor.Acta Pharm. 1977; 14: 95-104Google Scholar, 16Hallworth G.N. Andrews U.G. Size analysis of suspension inhalation by inertial separation methods.J Pharm Pharmacol. 1976; 28: 898-907Crossref PubMed Scopus (44) Google Scholar Aerosol samples were collected from the nebulizer through an 18-mm T-tube connector with an open side arm to compensate for pressure differences between nebulizer flow and the Andersen sampler 1 ACFM operating vacuum. The sampling device consisted of an 80-cm length of smooth bore, 22-mm diameter accordion tubing. Thirty centimeters from the Andersen sampler, a 15-cm sidearm was placed projecting back at 45° to the main tube and open at the end. Because of the greater negative pressure at the sampler, ambient air flowed into the main tube from the open sidearm. While there was some aerosol deposition on the walls of the tubing connector, Andersen sampler assays were performed on aerosols that would be delivered for patient inhalation.The Bec-DLPC liposomes in aerosols were collected in the Andersen sampler by impaction on a preseparator, eight aluminum stages of descending particle size, and a glass fiber collection filter below the smallest particle stage. Size range fractions collected were as follows: 10 µm; and greater in the preseparator; 9 to 10 µm; 5.8 to 9.0 µm; 4.7 to 5.8 µm; 3.3 to 4.7 µm; 2.1 to 3.3 µmm; 1.1 to 2.1 µm; 0.65 to 1.1 µmm; 0.43 to 0.65 µm; and less than 0.43 µmm on the final filter. The Bec-DLPC liposomes on the metal disks from each particle size stage, the preseparator, and the glass fiber filter were eluted for 20 min in 10 ml of absolute ethanol. The Bec-DP content of the samples was determined by HPLC assay.Table 1Nebulizer DataCompanyNebulizerAbbreviationInput Flow Rate, L/minNebulizer Volume, mlStarting Volume, mlAddressHospitakUp Mist Up Mst7.52091144 Route 109Power Mist Pw Mst7.5107Lindenhurst, NY 11757HudsonHand Held H-Hld7.517927711 Diaz RdNb Mst6.0107PO Box 9020Neb-U-MistAva Neb Ava Neb8.065Temecula, CA 92589MarquestRespirgard R-grd8.06611039 E Lansing CirAcorn Acra8.066Englewood, GO 80112Whisper Jet Wp Jet8.065MedicalAquatower A-twr10.015152879 R AvenueIndustriesPermanent Neb Pm Nb7.5107Adel, IA 50003AmericaCustom Neb Cm Nb7.586Pari-WerkPari-jet Pari15.065MoosstraBe 9GmbHD-8130Starnberg, GermanyPuritanSingle Jet SJ7.54020Lenexa DivisionBennettRaindrop Rd10.010710800 Pflumm Rd3040 304010.0106Lenexa, KS 66215ViratekSPAG SPAG15.0300203300 Hyland Ave,Costa Mesa, CA 92626SpiraSpira Spira6.02015Helsinki, FinlandVortran Medical Technology, IncHeart Heart10.0200241804 Tribute Rd Unit FSacramento, CA 95815 Open table in a new tab The Bec-DP concentrations were measured using an auto-sampler (Waters 710B WISP, Waters Division of Millipore, Milford, Mass) with a 3.9 × 150-mm column (Waters Nova-Pak C18) at room temperature. Beclomethasone dipropionate was detected at a wave length of 238 mm using a variable wave-length detector (Waters 486) with quantification on a data module integrator (Waters 746). The mobile phase was 50/50 water/ethanol at a flow rate of 0.8 ml/min.17Andersson P. Ryrfeldt A. Biotransformation of the topical glucocorticoids budesonide and beclomethasone 17a, 21-dipropionate in human liver and lung homogenate.J Pharm Pharmacol. 1984; 36: 763-765Crossref PubMed Scopus (78) Google Scholar Drug standards were prepared from ethanol stocks kept at 80°C. Assuming a log-normal particle distribution in the heterodisperse Bec-DLPC aerosols, the amount of drug recovered on each particle size stage was determined. These values were used to calculate the MMAD and GSD according to the Andersen sampler manufacturer's instructions (Andersen Instruments, Inc, Altanta) but using a computer program (Kaleida Graph 2.0, Synergy Software, Reading, Pa).The standard testing procedure was evaluated by performing 13 particle size determinations with a nebulizer (Puritan Bennett 1600) as modified to the single jet configuration (PBsj). For details, see Waldrep et al.12Waldrep JC, Scherer PW, Keyhani K, Knight V. Cyclosporin A liposome aerosol: particle size and calculated respiratory deposition. Int J Pharmaceut (in press)Google Scholar These nebulizers are equipped with ceramic jets and several different nebulizers were used in the tests. The mean MMAD ± GSD was 1.6 µm ± 2.2. The maximum and minimum 95 percent confidence limits of the MMAD were 1.7 and 1.4 µm. The 95 percent maximum and minimum confidence limits of the GSD were 2.3 and 2.1. These results indicate high uniformity of performance of the nebulizers and great consistency of the assay procedure. The validity of the Andersen sampler methodology was independently verified (using a model 3300 TSI Laser Particle Sizer). Three or more tests were performed for each nebulizer type. The results of each test were used to determine the mean MMAD, GSD, and Bec-DP output. A computer model originally developed by Persons et al18Persons D.D. Hess G.D. Muller W.J. Scherer P.W. Airway deposition of hygroscopic heterodispersed aerosols: results of a computer model.J Appl Physiol. 1987; 63: 1195-1204PubMed Google Scholar, 19Persons D.D. Hess G.D. Scherer P.W. Maximization of pulmonary hygroscopic aerosol deposition.J Appl Physiol. 1987; 63: 1205-1209PubMed Google Scholar was modified according to MMAD and GSD12Waldrep JC, Scherer PW, Keyhani K, Knight V. Cyclosporin A liposome aerosol: particle size and calculated respiratory deposition. Int J Pharmaceut (in press)Google Scholar and used to calculate regional deposition of the 18 aerosols. The human lung model was based on the following parameters: mouth breathing, functional residual volume 3,300 ml, tidal volume 750 ml, inspiration 2 s, expiration 2 s, no pause. Regional deposition was calculated for mouth and pharynx, conducting airways (Weibel model generations 0 to 16), and alveolated airways (Weibel model generations 17 to 23).20Weibel E.R. Morphometry of human lung. Academic Press, New York1963Crossref Google Scholar The aqueous suspension of Bec-DLPC liposomes approximated 0.5N (0.0045 g/ml) saline solution. Body weight was assumed to be 62.5 kg for calculation of dosage. The computer model results demonstrated good correlation with experimental regional deposition data from several investigators.18Persons D.D. Hess G.D. Muller W.J. Scherer P.W. Airway deposition of hygroscopic heterodispersed aerosols: results of a computer model.J Appl Physiol. 1987; 63: 1195-1204PubMed Google Scholar in fairly regular increments (from 0.9 to 7.2 µm) except for nebulizer No. 18 for which the MMAD was radically greater than the others. The GSD rises gradually from 1.8 to 2.8 with increasing MMAD.From the amount of Bec-DP recovered in 2.5 min from the Andersen sampler, the percentage of deposition for the mouth and Weibels generations 0 to 23 can be utilized to calculate the predicted Bec-DP levels deposited in each region. Figure 2 demonstrates the predicted percentage of regional deposition of the 18 The properties of the Bec-DLPC liposome aerosols produced by 18 nebulizers are shown in Tables 1 and 2. Nebulizers were ranked according to increasing MMAD of the particles, ranging from 0.9 to 7.2 µm. Table 2 also shows each corresponding GSD and the calculated regional deposition percentage of each aerosol predicted by the computer model for the mouth, generations 0 to 16 and 17 to 23 of human respiratory tract, as well as the total deposition. There is increased Bec-DP deposition in the mouth as the MMAD increases to 2.1 µm and higher. Increases in GSD also influence the predicted deposition patterns, particularly in the mouth and generations 0 to 16. Figure 1 is a graphic presentation from Table 2 to show the relative values of MMAD and corresponding GSD of the particles generated. The MMAD increases nebulizers. All nebulizers produced fairly uniform values for deposition within generations 17 to 23 with a mean value of 17.7 ± 1.9 percent. Deposition in the mouth and generations 0 to 16 increases gradually with increasing MMAD and GSD, except for the large increase with nebulizer No. 18.Table 2Characteristics of Bec-DLPC Liposome Aerosol Produced by 18 Different Nebulizers*Bec-DLPC=beclomethasone dipropionate-dilauroyl phosphatidylcholine; MMAD = mass median aerodynamic diameter; GSD = geometric standard deviation.% DepositionNo.NebulizerMMAD μm±50GSD±SD% Mouth and Throat% Generations 0-16†Reference 20.% Generations 17-23†Reference 20.% TotalBec, μg Recovery 2.5 min‡Mean drug recovery on eight stages of Andersen sampler in 2.5 min. ± SDNo. of Tests 1Rgrd0.9 ± 0.11.9 ± 0.20.21.912.014.1141 ± 373 2SPAG1.3 ± 0.31.8 ± 0.10.63.014.918.590 ± 103 3Rd1.3 ± 0.12.5 ± 0.23.04.616.123.7243 ± 633 4Pari1.5 ± 0.22.6 ± 0.34.05.416.726.1225 ± 953 530401.6 ± 0.52.5 ± 0.34.25.717.026.9294 ± 744 6SJ1.6 ± 0.22.2 ± 0.22.84.917.325.0147 ± 1913 7Nb Mist1.7 ± 0.32.1 ± 0.53.05.318.026.3187 ± 173 8Pw Mst1.7 ± 0.12.4 ± 0.34.96.217.828.9195 ± 563 9Acrn1.8 ± 0.42.5 ± 0.45.36.518.029.8219 ± 114410H-Hld2.0 ± 0.22.0 ± 0.23.66.119.629.3143 ± 21311Spira2.0 ± 0.62.1 ± 0.34.36.419.430.1190 ± 29312Ava Nb2.1 ± 0.42.5 ± 0.57.37.818.533.6272 ± 75313A-Twr2.1 ± 0.52.6 ± 0.67.98.118.534.580 ± 36314Pm Nb2.2 ± 0.62.5 ± 0.47.68.118.934.6171 ± 54415Cm Nb2.3 ± 0.32.3 ± 0.37.48.119.635.1148 ± 26316Wp Jt2.4 ± 0.42.8 ± 0.510.79.318.238.2295 ± 40317Up Mst2.7 ± 0.62.8 ± 0.512.110.218.540.8172 ± 11318Heart7.2 ± 0.74.7 ± 1.834.217.520.071.7239 ± 223* Bec-DLPC=beclomethasone dipropionate-dilauroyl phosphatidylcholine; MMAD = mass median aerodynamic diameter; GSD = geometric standard deviation.† Reference 20.‡ Mean drug recovery on eight stages of Andersen sampler in 2.5 min. Open table in a new tab Based on the amounts of Bec deposited within the Andersen sampler shown in Table 2, the estimated drug deposition at each regional area is shown in Figure 3. These data show greater variability among nebulizers than the percentage of deposition measurements since there is a wide range of total Bec output. Thus, while MMAD and GSD are major determinants of the site of deposition of aerosol particles within the respiratory track, the amount of drug delivered is a major feature of the nebulizer design and operation. Based on these analyses, nebulizers 3 to 12 show the greatest calculated deposition of Bec-DP in the alveolar region with the least calculated deposition in the mouth. The results of this study thus indicate that there is a wide range of operating characteristics among both nebulizer types and individual devices. Use of data such as presented herein will assist in selection of nebulizers best suited to a particular medical purpose. Jet nebulizers have typically been used to dispense water-soluble drugs from water or saline solution media. Many of the physical factors that control these aerosols have been studied, including the effect of air flow and pressure, changes in hygroscopicity resulting from dissolved salt or drugs, as well as design characteristics of the nebulizers. The ultimate properties controlling the medical use of aerosols, however, are the output of drug and the particle size of the aerosol. These properties can be measured conveniently and thus, comparisons among the various devices are possible. There is considerable variation in these properties among nebulizers used for water-soluble drugs. By analogy, when studies with liposome-drug preparations suspended in water were developed for aerosol use, it was deemed essential to determine the drug content and particle size of each such liposome-drug preparation in each nebulizer that might be used. In the present study, we have thus determined the MMAD, GSD, and drug output of Bec-DLPC for 18 different commercially available nebulizers. These data have been utilized in a computer lung model developed to estimate the regional Bec deposition in the respiratory tract.18Persons D.D. Hess G.D. Muller W.J. Scherer P.W. Airway deposition of hygroscopic heterodispersed aerosols: results of a computer model.J Appl Physiol. 1987; 63: 1195-1204PubMed Google Scholar, 19Persons D.D. Hess G.D. Scherer P.W. Maximization of pulmonary hygroscopic aerosol deposition.J Appl Physiol. 1987; 63: 1205-1209PubMed Google Scholar In general, for the most efficient of treatment of pulmonary diseases, a particle size range of 1 to 3 µm MMAD with a GSD of about 2.0 is recommended. Aerosol particles in this size are optimal because they are predicted by the computer lung model to deliver the largest dosage to peripheral lung sites. At the same time, predicted deposition of drug particles in the mouth and throat will be minimized. This distribution pattern is particularly advantageous for treatment of asthma with Bec-DLPC (or similar GC-liposome aerosols) where pharyngeal candidiasis or dysphonia may result from the deposition of GC particles administered from metered-dose inhalers. Moreover, drug deposited in the mouth, throat, and Weibel generations 0 to 16 is promptly cleared to the pharynx and swallowed and is available for systemic delivery.21Lippmann M. Schlesinger R.B. Interspecies comparisons of particle deposition and mucociliary clearance in tracheobronchial airways.J Toxicol Environ Health. 1984; 13: 441-469Crossref PubMed Scopus (98) Google Scholar This pattern can contribute to suppression of the hypophyseal-pituitary-adrenal axis.22Reid C.E. Aerosol steroids as primary treatment of mild asthma.N Engl J Med. 1991; 325: 425-426Crossref PubMed Scopus (40) Google Scholar, 23Szefler S.J. Glucocorticoid therapy for asthma: clinical pharmacology.J Allergy Clin Immunol. 1991; 88: 147-165Abstract Full Text PDF PubMed Scopus (83) Google Scholar Based on the results of this study with Bec-DLPC liposome aerosol, comparisons can be made among the numerous different devices and appropriate selections made for their optimal use. Selection of nebulizers for various forms of pulmonary therapy will, however, be based on a number of criteria in addition to the data presented herein, but fundamental to any selection is the foregoing methodology to estimate as to the regional deposition of aerosolized drug.24Bouchikhi A. Becquemin M.H. Bignon J. Roy M. Teillac A. Particle size of nine metered dose inhalers and their deposition probabilities in the airways.Eur Respir J. 1988; 1: 547-552PubMed Google Scholar It is apparent from this study that the majority of the nebulizers tested demonstrate acceptable performance characteristics. However, some nebulizers clearly were superior with respect to the predicted delivery of Bec-DLPC to peripheral lung, whereas some produced increased percentages of particles predicted to deposit in the mouth and throat. Some nebulizer variation was noted likely due to variations in their manufacturers. These studies have used Bec-DLPC as the prototype for GC-liposome aerosol formulations. Our results with Bec-DLPC are representative of similar studies carried out with other potent, topically active GCs: budesonide, triamcinolone acetonide, flunisolide, and dexamethasone (data not presented). However, differences in the total GC output and calculated deposition patterns have been noted when PC other than DLPC have been utilized for the liposome formulation. A similar pattern has been noted with cyclosporine liposome aerosol formulations.12Waldrep JC, Scherer PW, Keyhani K, Knight V. Cyclosporin A liposome aerosol: particle size and calculated respiratory deposition. Int J Pharmaceut (in press)Google Scholar Preliminary analysis of these same nebulizers with nonliposomal aqueous GC aerosols indicates differences in MMAD, GSD, and output between soluble and liposomal-encapsulated GCs. Further study is needed to delineate the reasons for these differences. The model used in this study was based on mouthin, mouth-out breathing. Calculations can also be made for nose-in, nose-out breathing, or combinations of nasal and mouth breathing. The present data are adequate, however, to compare the action of the nebulizers tested. Data for the other breathing modes can be obtained when needed. The use of aerosols for medical treatment is increasing and it seems possible that a number of lipid-soluble drugs can be administered in liposomal formulations. The results of this study are intended to assist in the development of such treatments.