Propellant-driven metered-dose inhalers for pulmonary drug delivery

Expert Opinion on Drug Delivery

Volumn 2, Issue 1, 2005, Pages 53-74

  Smyth, Hugh D C ^a  

^a UNIVERSITY OF NORTH CAROLINA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALCOHOL; APAFLURANE; BECLOMETASONE DIPROPIONATE; BUDESONIDE; CARBON DIOXIDE; CHLOROFLUOROCARBON; CROMOGLYCATE DISODIUM; CYCLODEXTRIN; DICHLORODIFLUOROMETHANE; EXCIPIENT; FENOTEROL; FENOTEROL PLUS IPRATROPIUM BROMIDE; FLUNISOLIDE; FLUORINATED HYDROCARBON; IPRATROPIUM BROMIDE; METHANE; NITROUS OXIDE; NORFLURANE; OLEIC ACID; PHOSPHATIDYLCHOLINE; PROPELLANT; SALBUTAMOL; SALMETEROL; SORBITAN TRIOLEATE; SURFACTANT; TRIAMCINOLONE ACETONIDE; TURBOHALER; VORICONAZOLE;

AEROSOL; AQUEOUS SOLUTION; ASTHMA; BIOEQUIVALENCE; BIOMEDICAL TECHNOLOGY ASSESSMENT; CLINICAL TRIAL; COMMERCIAL PHENOMENA; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG FORMULATION; ENVIRONMENTAL FACTOR; EQUIPMENT DESIGN; GENE THERAPY; GREENHOUSE EFFECT; HIGH RISK POPULATION; HUMAN; INHALATION SPACER; LUNG; MEDICAL NEBULIZER; METERED DOSE INHALER; OZONE LAYER; PARTICLE SIZE; PATENT; PERFORMANCE; POWDER INHALER; RESPIRATORY TRACT DISEASE; REVIEW; SIDE EFFECT; SYSTEMATIC REVIEW;

ADMINISTRATION, INHALATION; AEROSOL PROPELLANTS; AIR POLLUTANTS; ANIMALS; CHEMISTRY, PHARMACEUTICAL; CHLOROFLUOROCARBONS; DRUG DELIVERY SYSTEMS; EQUIPMENT DESIGN; HUMANS; HYDROCARBONS, FLUORINATED; LUNG; METERED DOSE INHALERS; NEBULIZERS AND VAPORIZERS; PARTICLE SIZE; PHARMACEUTICAL PREPARATIONS;

EID: 12344306183     PISSN: 17425247     EISSN: None     Source Type: Journal    
DOI: 10.1517/17425247.2.1.53     Document Type: Review

References (170)

1. GUPTA P, ADJEI A: Therapeutic inhalation aerosols. In: Inhalation Delivery of Therapeutic Peptides and Proteins. Adjei A, Gupta P (Ed.), Marcel Dekker, New York (1997): 185-229.
2. FINK JB: Metered-dose inhalers, dry powder inhalers, and transitions. Respir. Care (2000) 45(6):623-635.
3. COLTHORPE P: Industry experiences of the HFA transition. Drug Del. Syst. Sci. (2003) 3(9):41-43.
4. WINNIPS C, KELLER M: The role of pMDIs in pulmonary drug delivery. Innov. Pharm. Tech. (2000) 00(6):72-75.
5. BOULET LP: The ozone layer and metered dose inhalers. Can. Respir. J. (1998) 5(3):176-179.
6. TIWARI D, GOLDMAN D, DIXIT S, MALICK WA, MADAN PL: Compatibility evaluation of metered-dose inhaler valve elastomers with tetrafluoroethane (P134a), a non-CFC propellant. Drug Dev. Ind. Pharm. (1998) 24(4):345-352.
7. CUMMINGS RH: Pressurized metered dose inhalers: chlorofluorocarbon to hydrofluoroalkane transition-valve performance. J. Allergy Clin. Imm. (1999) 104(6):S230-S235.
8. BERRY J, KLINE L, NAINI V, CHAUDHRY S, HART J, SEQUEIRA J: Influence of the valve lubricant on the aerodynamic particle size of a metered dose inhaler. Drug Dev. Ind. Pharm. (2004) 30 3):267-275.
9. POLLI GP, GRIM WM, BACHER FA, YUNKER MH: Influence of formulation on aerosol particle size. J. Pharm. Sci. (1969) 58 Apr):484-486.
10. LEWIS D, JOHNSON S, MEAKIN B et al.: Effects of actuator orifice diameter on beclomethasone dipropionate delivery from a pMDI HFA solution formulation. Proceedings of Respiratory Drug Delivery VI Conference. (1998). 1:363-364.
11. RANUCCI JA, COOPER D, SETHACHUTKUL K: Effect of actuator design on metered-dose inhaler plume-particle size. Pharm. Tech. (1992) 16:90-92.
12. BRAMBILLA G, GANDERTON D, GARZIA R, LEWIS D, MEAKIN B, VENTURA P: Modulation of aerosol clouds produced by pressurised inhalation aerosols. Int. J. Pharm. (1999) 186(1):53-61.
13. WARREN SJ, FARR SJ: Formulation of solution metered dose inhalers and comparison with aerosols emitted from conventional suspension systems. Int. J. Pharm. (1995) 124(2):195-203.
14. SMYTH HDC: The influence of formulation variables on the performance of alternative propellant-driven metered dose inhalers. Adv. Drug Del. Rev. (2003) 55(7):807-828.
15. STEIN SW, MYRDAL PB: A theoretical and experimental analysis of formulation and device parameters affecting solution MDI size distributions. J. Pharm. Sci. (2004) 93(8):2158-2175.
16. USP24. < 601 > Aerosols, metered dose inhalers, and dry powder inhalers. The United States Pharmacopeia and National Formulary (2000):1895-1912.
17. CLARK AR: Metered atomization for respiratory drug delivery [Ph.D.]: Loughborough University of Technology, U.K. (1991).
18. DUNBAR CA, WATKINS AP, MILLER JF: Theoretical investigation of the spray from a pressurized metered-dose inhaler. Atomization Sprays (1997) 7(4):417-436.
19. DUNBAR CA, WATKINS AP, MILLER JF: An experimental investigation of the spray issued from a pMDI using laser diagnostic techniques. J. Aerosol. Med. (1997) 10(4):351-368.
20. FINLAY WH: The mechanics of inhaled pharmaceutical aerosols. Academic Press: London (2001).
21. SMYTH HDC, GALLION JA, GROVE JA, BRACE G, HICKEY AJ: Correlation of spray patterns with droplet size for pressurized metered dose inhalers. Paper presented at: Annual Meeting of American Association of Pharmaceutical Sciences. Toronto, Canada, Nov (2002).
22. CROMPTON GK: The adult patient's difficulties with inhalers. Lung (1990) 168(Suppl.):658-662.
23. WILKES W, FINK J, DHAND R: Selecting an accessory device with a metered-dose inhaler: variable influence of accessory devices on fine particle dose, throat deposition, and drug delivery with asynchronous actuation from a metered-dose inhaler. J. Aerosol. Med. (2001) 14:351-360.
24. BERG E, MADSEN J, BISGAARD H: In vitro performance of three combinations of spacers and pressurized metered dose inhalers for treatment in children. Eur. Resp. J. (1998) 12(2):472-476.
25. SMYTH HDC, BECK VP, WILLIAMS D, HICKEY AJ: The influence of formulation and spacer device on the in vitro performance of solution chlorofluorocarbon-free propellant-driven metered dose inhalers. AAPS PharmSciTech (2004) 5(1):Article 7.
26. JOHNSON DH, ROBART P: Inhaler technique of outpatients in the home. Respir. Care (2000) 45(10):1182-1187.
27. WILLIAMS RO, III, PATEL AM, BARRON MK, ROGERS TL: Investigation of some commercially available spacer devices for the delivery of glucocorticoid steroids from a pMDI. Drug Dev. Ind. Pharm. (2001) 27(5):401-412.
28. AHRENS R, LUX C, BAHL T, HAN S: Choosing the metered-dose inhaler spacer or holding chamber that matches the patient's need: evidence that the specific drug being delivered is an important consideration. J. Allergy Clin. Immunol. (1995) 96 2):288-294.
29. MITCHELL JP, NAGEL MW, RAU JL: Performance of large-volume versus small-volume holding chambers with chlorofluorocarbon-albuterol and hydrofluoroalkane-albuterol sulphate. Respir. Care (1999) 44 1):38-44.
30. WILDHABER JH, JANSSENS HM, PIERART F, DORE ND, DEVADASON SG, LESOUEF PN: High-percentage lung delivery in children from detergent-treated spacers. Paediatric Pulmonology (2000) 29 5):389-393.
31. PEART J, BYRON PR: Electrostatic properties of metered dose inhalers. Inst. Phys. Conf. Ser. (1999) 163(Electrostatics 1999):77-80.
32. WILDHABER JH, DEVADASON SG, HAYDEN MJ et al.: Electrostatic charge on a plastic spacer device influences the delivery of salbutamol. Eur. Respir. J. (1996) 9(9):1943-1946.
33. WILDHABER JH, DEVADASON SG, EBER E et al.: Effect of electrostatic charge, flow, delay and multiple actuations on the in vitro delivery of salbutamol from different small volume spacers for infants. Thorax (1996) 51(10):985-988.
34. WILDHABER JH, HAYDEN MJ, DORE ND, DEVADASON SG, LESOUEF PN: Salbutamol delivery from a hydrofluoroalkane pressurized metered-dose inhaler in paediatric ventilator circuits: an in vitro study. Chest (1998) 113(1):186-191.
35. PIERART F, WILDHABER JH, VRANCKEN I, DEVADASON SG, LE SOUEF PN: Washing plastic spacers in household detergent reduces electrostatic charge and greatly improves delivery. Eur. Resp. J. (1999) 13 3):673-678.
36. ANHOJ J, BISGAARD H, LIPWORTH BJ: Effect of electrostatic charge in plastic spacers on the lung delivery of HFA-salbutamol in children. Br. J. Clin. Pharmacol. (1999) 47(3):333-336.
37. DONNELL D: Inhaled corticosteroid delivery systems: clinical role of a breath-actuated device. Eur. Rev. Med. Pharmacol. Sci. (2001) 5(1):7-16.
38. VERVAET C, BYRON PR: Drug-surfactant-propellant interactions in HFA-formulations. Int. J. Pharm. (1999) 186(1):13-30.
39. DICKINSON PA, SEVILLE PC, MCHALE H, PERKINS NC, TAYLOR G: An investigation of the solubility of various compounds in the hydrofluoroalkane propellants and possible model liquid propellants. J. Aerosol. Med. (2000) 13(3):179-186.
40. CLARK A: Pulmonary delivery technology: recent advantages and potential for the new mellenium. In: Pharmaceutical Inhalation Aerosol Technology 2nd ed. Hickey A, (Ed.). Marcel Dekker: New York (2004).
41. SMYTH HDC, MEJIA-MILLAN EA, HICKEY AJ: The effect of ethanol on solvency vapor pressure, and emitted droplet size of solution metered dose inhalers containing HFA 134a. Respiratory Drug Delivery VIII (2002) 2:735-738.
42. HARRIS J, GUPTA A, MYRDAL PB: Application of a new method for analysis of solubility in HFA-134a. Respiratory Drug Delivery IX (2004) 3:725-728.
43. JOHNSON KA: Interfacial phenomena and phase behaviour in metered-dose inhaler formulations. In: Inhalation Aerosols. Hickey AJ (Ed). Marcel Dekker: New York (1996):385-415.
44. PUREWAL TS: Formulation of metered dose inhalers. In: Metered dose inhaler technology Interpharm. Purewal TS, Grant DJW (Eds.). Buffalo Grove, Il (1998).
45. ATKINS P: The development of new solution metered dose inhaler system. Paper presented at: Respiratory Drug Delivery II (1990) Keystone, CO.
46. SUAREZ S, HICKEY AJ: Drug properties affecting aerosol behaviour. Respir. Care (2000) 45(6):652-666.
47. TZOU TZ, PACHUTA RR, COY RB, SCHULTZ RK: Drug form selection in albuterol-containing metered-dose inhaler formulations and its impact on chemical and physical stability. J. Pharm. Sci. (1997) 86 12):1352-1357.
48. MICHAEL Y, SNOWDEN MJ, CHOWDHRY BZ, ASHURST IC, DAVIES-CUTTING CJ, RILEY T: Characterisation of the aggregation behaviour in a salmeterol and fluticasone propionate inhalation aerosol system. Int. J. Pharm. (2001) 221(1-2):165-174.
49. MICHAEL Y, CHOWDHRY BZ, ASHURST IC, SNOWDEN MJ, DAVIES-CUTTING C, GRAY S: The physico-chemical properties of salmeterol and fluticasone propionate in different solvent environments. Int. J. Pharm. (2000) 200(2):279-288.
50. STEFELY JS, BROWN B, HAMMERBECK DM, STEIN SW: Equiping the MDI for the 21st century by expanding its formulation options. Paper presented at: Respiratory Drug Delivery VIII (2002).
51. STEFELY JS, DUAN DC, BROWN BA, JOZWIAKOWSKI JP, RUBLE SA, SCHULTZ DW et al.: Surfactants designed for HFA-based MDIs. Proceeding of the 224th ACS National Meeting. Boston, MA, United States, 18-22 August, (2002) 2002:COLL-322.
52. ZHENG JY, FULU M-Y, LEE DY, BARBER TE, ADJEI AL: Pulmonary peptide delivery: effect of taste-masking excipients on leuprolide suspension metered-dose inhalers. Pharm. Dev. Technol. (2001) 6 4):521-530.
53. LAWRENCE MJ, REES GD: Microemulsion-based media as novel drug delivery systems. Adv. Drug Deliv. Rev. (2000) 45(1 ):89-121.
54. BUTZ N, PORTE C, COURRIER H, KRAFFT MP, VANDAMME TF: Reverse water-in-fluorocarbon emulsions for use in pressurized metered- dose inhalers containing hydrofluoroalkane propellants. Int. J. Pharm. (2002) 238(1-2):257-269.
55. DELLAMARY LA, TARARA TE, SMITH DJ et al.: Hollow porous particles in metered dose inhalers. Pharm. Res. (2000) 17 2):168-174.
56. WILLIAMS RO III, BARRON MK, JOSE ALONSO M, REMUNAN-LOPEZ C: Investigation of a pMDI system containing chitosan microspheres and P134a. Int. J. Pharm. (1998) 174(1-2):209-222.
57. DICKINSON PA, HOWELLS SW, KELLAWAY IW: Novel nanoparticles for pulmonary drug administration. J. Drug Target. (2001) 9 4):295-302.
58. SOMMERVILLE ML, HICKEY AJ: Aerosol generation by metered-dose inhalers containing dimethyl ether/propane inverse microemulsions. AAPS Pharm. Sci. Tech. (2003) 4(4).
59. FASSBERG J, SEQUEIRA J, CHAUDHRY IA, KOPCHA M, INVENTORS: Non-chlorofluorocarbon aerosol formulation. (1995).
60. PUREWAL TS, GREENLEAF DJ, INVENTORS: Medical Aerosol Formulations. (1997).
61. BOWMAN PA, GREENLEAF D: Non-CFC metered dose inhalers: the patent landscape. Int. J. Pharm. (1999) 186(1):91-94.
62. LEACH C: Enhanced drug delivery through reformulating MDIs with HFA propellants-drug deposition and its effect on preclinical and clinical programs. Proceeding of the Respiratory Drug Delivery V Program. 1996:133-144.
63. CORREN J, TASHKIN DP: Evaluation of efficacy and safety of flunisolide hydrofluoroalkane for the treatment of asthma. Clin. Ther. (2003) 25(3):776-798.
64. BARRY PW, O'CALLAGHAN C: The influence of inhaler selection on efficacy of asthma therapies. Adv. Drug. Del. Rev. (2003) 55 7):879-923.
65. DUBUS JC, RHEM R, DOLOVICH M: Delivery of HFA and CFC salbutamol from spacer devices used in infancy. Int. J. Pharm. (2001) 222(1):101-108.
66. JENKINS M: Clinical evaluation of CFC-free metered dose inhalers. J. Aerosol. Med. (1995) 8(Suppl. 1):S41-S47.
67. KLEERUP EC, TASHKIN DP, CLINE AC, EKHOLM BP: Cumulative dose-response study of non-CFC propellant HFA 134a salbutamol sulphate metered-dose inhaler in patients with asthma. Chest (1996) 109 3):702-707.
68. DAHL R, RINGDAL N, WARD SM, STAMPONE P, DONNELL D: Equivalence of asthma control with new CFC-free formulation HFA-134a beclomethasone dipropionate and CFC-beclomethasone dipropionate. Br. J. Clin. Pract. (1997) 51(1):11-15.
69. DOCKHORN RJ, WAGNER DE, BURGESS GL, HAFNER KB, LETOURNEAU K, COLICE GL et al.: Proventil HFA provides protection from exercise-induced bronchoconstriction comparable to proventil and ventolin. Ann. Allergy Asthma Immunol. (1997) 79(1):85-88.
70. MAESEN FP, GREEFHORST LP, SMEETS JJ, WALD FD, CORNELISSEN PJ: Therapeutic equivalence of a novel HFA 134a-containing metered-dose inhaler and the conventional CFC inhaler (Berodual) for the delivery of a fixed combination of fenoterol/ipratropium bromide. A randomized double-blind placebo-controlled crossover study in patients with asthma. Respiration (1997) 64(4):273-280.
71. NOGAMI-ITOH M, YAKUO I, HAMMERBECK DM, MILLER RL, TAKEYAMA K: The equivalent bronchodilator effects of salbutamol formulated in chlorofluorocarbon and hydrofluoroalkane-134a metered dose inhalers on the histamine-induced pulmonary response in dogs. Pharm. Res. (1997) 14(2):208-212.
72. BLUMENTHAL MN, CASALE TB, FINK JN, URYNIAK T, CASTY FE: Evaluation of a non-chlorofluorocarbon formulation of cromolyn sodium (Intal) metered-dose inhaler versus the chlorofluorocarbon formulation in the treatment of adult patients with asthma: a controlled trial. J. Allergy Clin. Immunol. (1998) 101(1 Pt 1):7-13.
73. DAVIES RJ, STAMPONE P, O'CONNOR BJ: Hydrofluoroalkane-134a beclomethasone dipropionate extrafine aerosol provides equivalent asthma control to chlorofluorocarbon beclomethasone dipropionate at approximately half the total daily dose. Respir. Med. (1998) 92 Suppl. A):23-31.
74. HERMANN R, RUUS P, SCHNEIDER E, De MEY C: Tolerability and in vivo performance of a novel freon-free metered dose inhaler for a fixed combinational product of reproterol and disodium cromoglycate. Arzneimittelforschung (1998) 48(6):663-667.
75. LEACH CL, DAVIDSON PJ, BOUDREAU RJ: Improved airway targeting with the CFC-free HFA-beclomethasone metered- dose inhaler compared with CFC-beclomethasone. Eur. Respir. J. (1998) 12(6):1346-1353.
76. RAMSDELL JW, COLICE GL, EKHOLM BP, KLINGER NM: Cumulative dose response study comparing HFA-134a albuterol sulphate and conventional CFC albuterol in patients with asthma. Ann. Allergy Ashtma Immunol. (1998) 81(6):593-599.
77. SEALE JP, HARRISON LI: Effect of changing the fine particle mass of inhaled beclomethasone dipropionate on intrapulmonary deposition and pharmacokinetics. Respir. Med. (1998) 92(Suppl. A ):9-15.
78. THOMPSON PJ, DAVIES RJ, YOUNG WF, GROSSMAN AB, DONNELL D: Safety of hydrofluoroalkane-134a beclomethasone dipropionate extrafine aerosol. Respir. Med. (1998) 92(Suppl. A):33-39.
79. AYRES JG, SIMMONS JL, STAMPONE P: Acute safety of beclomethasone dipropionate in a new CFC-free propellant system in asthmatic patients. Respir. Med. (1999) 93(1):27-32.
80. BRONSKY E, EKHOLM BP, KLINGER NM, COLICE GL: Switching patients with asthma from chlorofluorocarbon (CFC) albuterol to hydrofluoroalkane-134a (HFA) albuterol. J. Asthma (1999) 36 1):107-114.
81. BUSSE WW, BRAZINSKY S, JACOBSON K et al.: Efficacy response of inhaled beclomethasone dipropionate in asthma is proportional to dose and is improved by formulation with a new propellant. J. Allergy Clin. Immunol. (1999) 104(6):1215-1222.
82. COLICE GL, KLINGER NM, EKHOLM BP, DOCKHORN RJ: Proventil HFA prevents exercise-induced bronchoconstriction in children. J. Asthma (1999) 36(8):671-676.
83. DEMEDTS M, COHEN R, HAWKINSON R: Switch to non-CFC inhaled corticosteroids: a comparative efficacy study of HFA-BDP and CFC-BDP metered-dose inhalers. Int. J. Clin. Pract. (1999) 53 5):331-338.
84. FURUKAWA C, ATKINSON D, FORSTER TJ, NAZZARIO K, SIMPSON B, URYNIAK T et al.: Controlled trial of two formulations of cromolyn sodium in the treatment of asthmatic patients > or = 12 years of age. Intal Study Group. Chest (1999) 116(1):65-72.
85. GOLDIN JG, TASHKIN DP, KLEERUP EC et al.: Comparative effects of hydrofluoroalkane and chlorofluorocarbon beclomethasone dipropionate inhalation on small airways: assessment with functional helical thin-section computed tomography. J. Allergy Clin. Immunol. (1999) 104(6):S258-S267.
86. GROSS G, THOMPSON PJ, CHERVINSKY P, VANDEN BURGT J: Hydrofluoroalkane-134a beclomethasone dipropionate, 400 microg, is as effective as chlorofluorocarbon beclomethasone dipropionate, 800 microg, for the treatment of moderate asthma. Chest (1999) 115 2):343-351.
87. HARRISON LI, SORIA I, CLINE AC, EKHOLM BP: Pharmacokinetic differences between chlorofluorocarbon and chlorofluorocarbon-free metered dose inhalers of beclomethasone dipropionate in adult asthmatics. J. Pharm. Pharmacol. (1999) 51(11):1235-1240.
88. JACOBSON K, CHERVINSKY P, NOONAN M, KANE RE, BANERJI D, URYNIAK T: Placebo-controlled, comparative study of the efficacy and safety of triamcinolone acetonide inhalation aerosol with the non-CFC propellant HFA-134a in patients with asthma. Azmacort HFA Clinical Study Group. Ann. Allergy Asthma Immunol. (1999) 83(4):327-333.
89. JUNIPER EF, BUIST AS: Health-related quality of life in moderate asthma: 400 μm hydrofluoroalkane beclomethasone dipropionate versus 800 microg chlorofluorocarbon beclomethasone dipropionate. The Study Group. Chest (1999) 116(5):1297-1303.
90. MILANOWSKI J, QUALTROUGH J, PERRIN VL: Inhaled beclomethasone (BDP) with non-CFC propellant (HFA 134a) is equivalent to BDP-CFC for the treatment of asthma. Respir. Med. (1999) 93(4):245-251.
91. PARAMESWARAN KN, INMAN MD, EKHOLM BP et al.: Protection against methacholine bronchoconstriction to assess relative potency of inhaled beta2-agonist. Am. J. Respir. Crit. Care Med. (1999) 160 1):354-347.
92. RAMSDELL JW, KLINGER NM, EKHOLM BP, COLICE GL: Safety of long-term treatment with HFA albuterol. Chest (1999) 115 4):945-951.
93. AYRES JG, MILLAR AB, SYKES AP: Clinical efficacy and safety of fluticasone propionate 1 mg twice daily administered via a HFA 134a pressurized metered dose inhaler to patients with severe asthma. U.K. study group. Respir. Med. (2000) 94(Suppl. B):S42-S50.
94. BATEMAN ED, ADLER L, CHYREK-BOROWSKA S et al.: Inhaled triamcinolone acetonide HFA 450 mcg twice daily compared with beclomethasone dipropionate CFC 500 mcg twice daily in adults with moderate persistent asthma. Clin. Drug Inv. (2000) 20:9-17.
95. BAUMGARTEN CR, DOROW P, WEBER HH, GEBHARDT R, KETTNER J, SYKES AP: Equivalence of as-required salbutamol propelled by propellants 11 and 12 or HFA 134a in mild to moderate asthmatics. German Study Group. Respir. Med. (2000) 94(Suppl. B):S17-S21.
96. BOCCUZZI SJ, WOGEN J, ROEHM JB: Use of hydrofluoroalkane propellant delivery system for inhaled albuterol in patients receiving asthma medications. Clin. Ther. (2000) 22(2):237-247.
97. FARMER IS, MIDDLE M, SAVIC J, PERRI VL, HERDMAN MJ: Therapeutic equivalence of inhaled beclomethasone dipropionate with CFC and non-CFC (HFA 134a) propellants both delivered via the Easibreathe inhaler for the treatment of paediatric asthma. Respir. Med. (2000) 94(1):57-63.
98. GOLDBERG J, BOHNING W, SCHMIDT P, FREUND E: Fenoterol hydrobromide delivered via HFA-MDI or CFC-MDI in patients with asthma: a safety and efficacy comparison. Respir. Med. (2000) 94 10):948-953.
99. HUCHON G, HOFBAUER P, CANNIZZARO G, IACONO P, WALD F: Comparison of the safety of drug delivery via HFA- and CFC-metered dose inhalers in CAO. Eur. Respir. J. (2000) 15(4):663-669.
100. KUNKA R, ANDREWS S, PIMAZZONI M et al.: From hydrofluoroalkane pressurized metered dose inhalers (pMDIs) and comparability with chlorofluorocarbon pMDIs. Respir. Med. (2000) 94(Suppl. B):S10-S16.
101. MACKIE AE, MCDOWALL JE, VENTRESCA P, BYE A, FALCOZ C, DALEY-YATES PT: Systemic exposure to fluticasone propionate administered via metered dose inhaler containing chlorofluorocarbon or hydrofluoroalcane propellant. Clin. Pharmacokinet. (2000) 39 Suppl. 1):17-22.
102. MAGNUSSEN H: Equivalent asthma control after dose reduction with HFA-134a beclomethasone solution aerosol. Comparative Inhaled Steroid Investigation Group (CISIG). Respir. Med. (2000) 94 6):549-555.
103. NELSON HS, KANE RE, PETILLO J, BANERJI D: Long-term safety of a non-chlorofluorocarbon-containing triamcinolone acetonide inhalation aerosol in patients with asthma. Azmacort HFA Study Group. J. Asthma (2000) 37(2):145-152.
104. PERRUCHOUD AP, LUNDBACK B, YIGLA M, SYKES AP: Clinical efficacy and safety of fluticasone propionate 1 mg per day administered via a HFA 134a pressurized metered dose inhaler to patients with moderate to severe asthma. International study group. Respir. Med. (2000) 94 (Suppl. B):S35-S41.
105. SHAPIRO G, BRONSKY E, MURRAY A, BARNHART F, VANDERMEER A, REISNER C: Clinical comparability of ventolin formulated with hydrofluoroalkane or conventional chlorofluorocarbon propellants in children with asthma. Arch. Pediatr. Adolesc. Med. (2000) 154 12):1219-1225.
106. TONNEL AB, BONS J, LEGENDRE M et al.: Clinical efficacy and safety of fluticasone propionate 250 μm twice daily administered via a HFA 134a pressurized metered dose inhaler to patients with mild to moderate asthma. French study group. Respir. Med. (2000) 94 Suppl. B):S29-S34.
107. AUBIER M, WETTENGER R, GANS SJ: Efficacy of HFA-beclomethasone dipropionate extra-fine aerosol (800 microg day(-1)) versus HFA-fluticasone propionate (1000 μm day(-1)) in patients with asthma. Respir. Med. (2001) 95(3):212-220.
108. CASALE TB, NELSON HS, CORREN J, NEWMAN K: Long-term safety of flunisolide hydrofluoroalkane metered-dose inhaler in adults and adolescents with asthma. Clin. Drug Inv. (2001) 21:755-764.
109. FIREMAN P, PRENNER BM, VINCKEN W, DEMEDTS M, MOL SJ, COHEN RM: Long-term safety and efficacy of a chlorofluorocarbon-free beclomethasone dipropionate extrafine aerosol. Ann. Allergy Asthma Immunol. (2001) 86(5):557-565.
110. LUMRY W, NOVECK R, WEINSTEIN S et al.: Switching from Ventolin CFC to Ventolin HFA is well tolerated and effective in patients with asthma. Ann. Allergy Asthma Immunol (2001) 86 3):297-303.
111. NOLTING A, SISTA S, ABRAMOWITZ W. Flunisolide HFA versus flunisolide CFC: pharmacokinetic comparison in healthy volunteers. Biopharm. Drug Dispos. (2001) 22(9):373-382.
112. TAYLOR J, KOTCH A, RICE K et al.: Ipratropium bromide hydrofluoroalkane inhalation aerosol is safe and effective in patients with COPD. Chest (2001) 120(4):1253-1261.
113. WORTH H, MUIR JF, PIETERS WR: Comparison of hydrofluoroalkane-beclomethasone dipropionate Autolhaler with budesonide Turbuhaler in asthma control. Respiration (2001) 68 5):517-526.
114. ANDERSON PB, LANGLEY SJ, MOONEY P, JONES J, Addles Tone R, ROSSETTI A et al.: Equivalent efficacy and safety of a new HFA-134a formulation of BDP compared with the conventional CFC in adult asthmatics. J. Investig. Allergol. Clin. Immunol. (2002) 12 2):107-113.
115. BOUSQUET J, CANTINI L: Clinical studies in asthmatics with a new non-extra fine HFA formulation of beclometasone dipropionate (BDP Modulite). Respir. Med. (2002) 96(Suppl. D):S17-S27.
116. FOWLER SJ, ORR LC, SIMS EJ et al.: Therapeutic ratio of hydrofluoroalkane and chlorofluorocarbon formulations of fluticasone propionate. Chest (2002) 122(2):618-623.
117. HAWKSWORTH RJ, SYKES AP, FARIS M, MANT T, LEE TH: Albuterol HFA is as effective as albuterol CFC in preventing exercise-induced bronchoconstriction. Ann. Allergy Asthma Immunol. (2002) 88 5):473-477.
118. JUNIPER EF, PRICE DB, STAMPONE PA, CREEMERS JP, MOL SJ, FIREMAN P: Clinically important improvements in asthma-specific quality of life, but no difference in conventional clinical indexes in patients changed from conventional beclomethasone dipropionate to approximately half the dose of extrafine beclomethasone dipropionate. Chest (2002) 121(6):1824-1832.
119. LANGLEY SJ, SYKES AP, BATTY EP, MASTERSON CM, WOODCOCK A: A comparison of the efficacy and tolerability of single doses of HFA 134a albuterol and CFC albuterol in mild-to-moderate asthmatic patients. Ann. Allergy Asthma Immunol. (2002) 88(5):488-493.
120. LEACH CL, DAVIDSON PJ, HASSELQUIST BE, BOUDREAU RJ: Lung deposition of hydrofluoroalkane-134a beclomethasone is greater than that of chlorofluorocarbon fluticasone and chlorofluorocarbon beclomethasone: a cross-over study in healthy volunteers. Chest (2002) 122 2):510-516.
121. NOLTING A, SISTA S, ABRAMOWITZ W: Single-dose study to compare the pharmacokinetics of HFA flunisolide and CFC flunisolide. J. Pharm. Sci. (2002) 91(2):424-432.
122. PRICE D, HAUGHNEY J, DUERDEN M, NICHOLLS C, MOSELEY C: The cost effectiveness of chlorofluorocarbon-free beclomethasone dipropionate in the treatment of chronic asthma: a cost model based on a 1-year pragmatic, randomised clinical study. Pharmacoeconomics (2002) 20(10):653-664.
123. SZEFLER SJ, WARNER J, STAAB D, WAHN U, LE BOURGEOIS M, VAN ESSEN-ZANDVLIET EE et al.: Switching from conventional to extrafine aerosol beclomethasone dipropionate therapy in children: a 6-month, open- label, randomized trial. J. Allergy Clin. Immunol. (2002) 110 1):45-50.
124. JOGUPARTHI V, BREEN P, COMPADRE C et al.: Effect of Propellant on the Pharmacokinetics and Pharmacodynamics of Inhaled Albuterol in Asthmatic Subjects. J. Aerosol Med. (2003) 16 1):47-53.
125. BRAZINSKY SA, LAPIDUS RJ, WEISS LA, GHAFOURI M, FAGAN NM, WITEK TJ: One-year evaluation of the safety and efficacy of ipratropium bromide HFA and CFC inhalation aerosols in patients with chronic obstructive pulmonary disease. Clin. Drug Inv. (2003) 23 3):181-191.
126. GRZELEWSKA-RZYMOWSKA I, MALOLEPSZY J, De MOLINA M, SLADEK K, ZARKOVICE J, SIERGIEJKO Z: Equivalent asthma control and systemic safety of inhaled budesonide delivered via HFA-134a or CFC propellant in a broad range of doses. Respir. Med. (2003) 97 (Suppl. D):S10-S19.
127. LYTTLE B, GILLES J, PANOV M, EMERYK A, WIXON C: Fluticasone propionate 100 microg bid using a non-CFC propellant, HFA 134a, in asthmatic children. Can. Respir. J. (2003) 10(2):103-109.
128. HOLZ O, ZUHLKE I, EINHAUS M et al.: Direct measurement of BDP and 17-BMP in bronchial and peripheral lung tissue after inhalation of HFA- versus CFC-driven aerosols. Pulm. Pharmacol. Therapeutics (2004) 17(4):233-238.
129. VAN NOORD JA, LILL H, DIAZ TC, GREEFHORST AP, DAVIES P: Clinical equivalence of a salmeterol/fluticasone propionate combination product (50/500mg) delivered via a chlorofluorocarbon-free metered-dose inhaler with the diskus in patients with moderate to severe asthma. Clin. Drug Inv. (2001) 21(4):243-255.
130. ARGENTI D, SHAH B, HEALD D: A study comparing the clinical pharmacokinetics, pharmacodynamics, and tolerability of triamcinolone acetonide HFA-134a metered-dose inhaler and budesonide dry-powder inhaler following inhalation administration. J. Clin. Pharmacol. (2000) 40(5):516-526.
131. GUSTAFSSON P, KALLMAN S, WHITEHEAD PJ: Clinical equivalence between salbutamol hydrofluoroalkane pMDI and salbutamol Turbuhaler at the same cumulative microgram doses in paediatric patients. Respir. Med. (2002) 96(11):957-959.
132. AFFRIME MB, CUSS F, PADHI D et al.: Bioavailability and metabolism of mometasone furoate following administration by metered-dose and dry-powder inhalers in healthy human volunteers. J. Clin. Pharmacol. (2000) 40(11):1227-1236.
133. LIPWORTH BJ, CLARKE DJ: Lung delivery of salbutamol by dry powder inhaler (Turbuhaler) and small volume antistatic metal spacer (Airomir CFC-free MDI plus NebuChamber). Eur. Respir. J. (1997) 10(8):1820-1823.
134. SZEFLER SJ, MARTIN RJ, KING TS et al.: Significant variability in response to inhaled corticosteroids for persistent asthma. J. Allergy Clin. Immunol. (2002) 109(3):410-418.
135. ADLER LM, ANAND C, WRIGHT FGDL et al.: Efficacy and tolerability of beclomethasone dipropionate delivered by a novel multidose dry powder inhaler (Clickhaler) versus a metered-dose inhaler in children with asthma. Current Therapeutic Research (2001) 62 11):758-769.
136. NATHAN RA, NAYAK AS, GRAFT DF et al.: Mometasone furoate: efficacy and safety in moderate asthma compared with beclomethasone dipropionate. Ann. Allergy Asthma Immunol. (2001) 86(2):203-210.
137. AFFRIME MB, KOSOGLOU T, THONOOR CM, FLANNERY BE, HERRON JM: Mometasone furoate has minimal effects on the hypothalamic-pituitary-adrenal axis when delivered at high doses. Chest (2000) 118(6):1538-1546.
138. NELSON H, KEMP JP, BIELER S, VAUGHAN LM, HILL MR: Comparative efficacy and safety of albuterol sulphate Spiros inhaler and albuterol metered-dose inhaler in asthma. Chest (1999) 115(2 ):329-335.
139. CHEGE JK, PARRY-BILLINGS M, CHRYSTYN H: Relative bioavailability of salbutamol to the lung following inhalation via two versions of a novel dry powder inhaler (Clickhaler) and a standard pressurized metered dose inhaler (Ventolin). Pharm. Pharmacol. Com. (1998) 4(2):107-109.
140. HINDLE M, PEERS EM, PARRY-BILLINGS M, CHRYSTYN H: Relative bioavailability of salbutamol to the lung following inhalation via a novel dry powder inhaler and a standard metered dose inhaler. Br. J. Clin. Pharmacol. (1997) 43(3):336-338.
141. VON BERG A, JEENA P, SOEMANTRI PA et al.: Efficacy and safety of ipratropium bromide plus fenoterol inhaled via Respimat Soft Mist Inhaler versus a conventional metered dose inhaler plus spacer in children with asthma. Pediatr. Pulmonol. (2004) 37 3):264-272.
142. VINCKEN W, BANTJE T, MIDDLE MV, GERKEN F, MOONEN D: Long-term efficacy and safety of ipratropium bromide plus fenoterol via Respimat soft Mist Inhaler (SMI) versus a pressurized metered-dose inhaler in asthma. Clin. Drug Inv. (2004) 24(1):17-28.
143. VINCKEN W, DEWBERRY H, MOONEN D: Fenoterol delivery by respimat soft mist inhaler versus CFC metered dose inhaler: cumulative dose-response study in asthma patients. J. Asthma (2003) 40 6):721-730.
144. GOLDBERG J, FREUND E, BECKERS B, HINZMANN R: Improved delivery of fenoterol plus ipratropium bromide using Respimat compared with a conventional metered dose inhaler. Eur. Respir. J. (2001) 17(2):225-232.
145. KILFEATHER SA, PONITZ HH, BECK E et al.: Improved delivery of ipratropium bromide/fenoterol from Respimat Soft Mist Inhaler in patients with COPD. Respir. Med. (2004) 98(5):387-397.
146. EVERARD ML: CFC transition: the Emperor's new clothes. Each class of drug deserves a delivery system that meets its own requirements. Thorax (2000) 55:811-814.
147. RAM FS, BROCKLEBANK DM, WHITE J, WRIGHT JP, JONES PW: Pressurised metered dose inhalers versus all other hand-held inhaler devices to deliver beta-2 agonist bronchodilators for non-acute asthma. Cochrane Database Syst. Rev. (2002) 1.
148. BROCKLEBANK D, RAM F, WRIGHT J, BARRY P, CATES C, DAVIES L et al.: Comparison of the effectiveness of inhaler devices in asthma and chronic obstructive airways disease: a systematic review of the literature. Health Technol. Assessment (2001) 5(26 ):1-149.
149. HARTUNG TK, ALLBUTT H, DEWAR M, INNES JA, CROMPTON GK: Moving from CFC aerosol to HFA aerosol or dry powder inhalers: what do patients think? Respiration (2002) 69(4):314-319.
150. MOLINA MJ, ROWLAND FS: Stratospheric sink for chlorofluoromethane: chlorine atom catalysed destruction of ozone. Nature (1974) 274:810-812.
151. FORTE R, Jr., DIBBLE C: The role of international environmental agreements in metered-dose inhaler technology changes. J. Allergy Clin. Immunol. (1999) 104(6):S217-S220.
152. COLE CH: Special Problems in Aerosol Delivery: Neonatal and paediatric considerations. Respir. Care (2000) 45(6 ):646-651.
153. EVERARD ML: Inhalation Therapy for Infants. Adv. Drug Del. Rev. (2003) 55:869-878.
154. HELMS PJ, CHRISTIE G: Prospects for preventing asthma. Archives Dis. Childhood (1999) 80(5):401-404.
155. HUELS G, MUELLER M, VON BREDOW C et al.: Long term efficacy of aerosolized amiloride in paediatric patients with cystic fibrosis. Proceedings of the 24th European Cyctic Fibrosis Conference Genoa, Italy, 20-23 June, (2002) 2002:251-253.
156. ROSENFELD M, GIBSON R, MCNAMARA S, EMERSON J, MCCOY KS, SHELL R et al.: Serum and lower respiratory tract drug concentrations after tobramycin inhalation in young children with cystic fibrosis. J. Pediatr. (2001) 139(4):572-577.
157. ENGLUND JA, PIEDRA PA, WHIMBEY E: Prevention and treatment of respiratory syncytial virus and parainfluenza viruses in immunocompromised patients. Am. J. Med. (1997) 102(3A ):61-70.
158. COLE CH, COLTON T, SHAH BL et al.: Early inhaled glucocorticoid therapy to prevent bronchopulmonary dysplasia. N. Engl. J. Med. (1999) 340(13):1005-1010.
159. GONDA I: Targeting by Deposition. In: Pharmaceutical Aerosol Inhalation Technology. 2nd ed. Hickey AJ, (Ed). Marcel Dekker: New York (2004):65-88.
160. DOLOVICH M: Aerosol delivery to children: what to use, how to choose. Paediatr. Pulmonol. (1999) 18:79-82.
161. DEVADASON SG, EVERARD ML, MACEARLAN C et al.: Lung deposition from the Turbuhaler in children with cystic fibrosis. Eur. Respir. J. (1997) 10(9):2023-2028.
162. WILDHABER JH, DEVADASON SG, WILSON JM et al.: Lung
163. WILDHABER JH, DEVADASON SG, HAYDEN MJ, EBER E, SUMMERS QA, LESOUEF PN: Aerosol delivery to wheezy infants: a comparison between a nebulizer and two small volume spacers. Paediatr. Pulmonol. (1997) 23(3):212-216.
164. IQBAL S, RITSON S, PRINCE I, DENYER J, EVERARD MARK L: Drug delivery and adherence in young children. Paediatr. Pulmonol. (2004) 37(4):311-317.
165. AMIRAV I, MANSOUR Y, MANDLEBERG A, BAR-IIAN I, NEWHOUSE M: Redesigned Face Mask Improves "Real Life" Aerosol Delivery for Nebuchamber. Pediar. Pulmonol. (2004) 37:172-177.
166. AMIRAV I, NEWHOUSE MT: Aerosol therapy with valved holding chambers in young children: importance of the facemask seal. Paediatrics (2001) 108(2):389-394.
167. JANSSENS HM, DEVADASON SG, HOP WC, LESOUEF PN, DE JONGSTE JC, TIDDENS HA: Variability of aerosol delivery via spacer devices in young asthmatic children in daily life. Eur. Res. J. (1999) 13 4):787-791.
168. WILSON EO: The Bottleneck. Sci. Am. 2002 Feburary.
169. AMES SA, GLEESON CD, KIRKPATRICK P: Omalizumab. Nat Rev. Drug Discov. (2004) 3(3):199-200.
170. CROWDER TM: Vibration Technology for Active Dry-Powder Inhalers. Pharm. Technol. (2004):52-61.