Inhalation Devices and Pulmonary Drug Delivery


Pulmonary drug delivery




Inhaled drug delivery is mainly used to treat pulmonary airway disorders by transporting the drug directly to its targeted location for action. This decreases the dose required to exert a therapeutic effect and minimizes any potential adverse effects. Direct drug delivery to air passages facilitates a faster onset of action; it also minimizes irritation to the stomach, which frequently occurs with oral medications, and prevents the exposure of drugs to pre-systemic metabolism that takes place in the intestine and liver. In addition to that, the lung is regarded as a route for transporting medications throughout the entire body’s blood circulation. The type of medication and the device used to deliver it are both important elements in carrying the drug to its target in the lungs. Different types of inhalation methods are used in inhaled delivery. They differ in the dose delivered, inhalation technique, and other factors. This paper will discuss these factors in more detail. 


Hillery AM, Lloyd AW, Swarbrick J, 2001, Pulmonary Drug Delivery, in Drug delivery and Targeting for Pharmacists and Pharmaceutical Scientists, Taylor & Francis, London, 269-300.

Dhand R, Fink JB, 1999, Dry Powder Inhalers. Respir Care, 44(8): 940-951.

Terzano C, 2001, Pressurized Metered Dose Inhalers and Add-on Devices. Pulmonary Pharmacology & Therapeutics, 14(5): 351-366.

Barnes PJ, 2004, The Size of the Problem of Managing Asthma. Respir Med, 98(Supplement 2): S4-S8.

Chrystyn H, 2007, The DiskusTM: A Review of Its Position Among Dry Powder Inhaler Devices. Int J Clin Pract, 61(6): 1022-1036.

McCallion ONM, Taylora KMG, Bridges PA, et al., 1996, Jet Nebulisers for Pulmonary Drug Delivery. Int J Pharm, 130(1): 1-11.

Taylor KMG, McCallion ONM, 1997, Ultrasonic Nebulisers for Pulmonary Drug Delivery. Int J Pharm, 153(1): 93-104.

McCallion ONM, Patel MJ, 1996, Viscosity Effects on Nebulisation of Aqueous Solutions. Int J Pharm, 130(2): 245-249.

Mercer TT, 1981, Production of Therapeutic Aerosols; Principles and Techniques. Chest, 80(6 Suppl): 813-818.

Dhand R, Tobin MJ, 1997, Inhaled Bronchodilator Therapy in Mechanically Ventilated Patients. Am J Respir Crit Care Med, 156(1): 3-10.

Ferron GA, Kerrebijn KF, Weber J, 1976, Properties of Aerosols Produced with Three Nebulizers. Am Rev Respir Dis, 114(5): 899-908.

Taylor KMG, Venthoye G, Chawla A, 1992, Pentamidine Isethionate Delivery from Jet Nebulisers. Int J Pharm, 85(1-3): 203-208.

Clay MM, Pavia D, Newman SP, et al., 1983, Assessment of Jet Nebulisers for Lung Aerosol Therapy. Lancet, 2(8350): 592-594.

Mercer TT, 1973, Production and Characterization of Aerosols. Arch Intern Med, 131(1): 39-50.

Cipolla DC, Clark AR, Chan HK, et al., 1994, Assessment of Aerosol Delivery Systems for Recombinant Human Deoxyribonuclease. STP Pharm Sci, 4(1): 50-62.

Waldrep JC, Keyhani K, Black M, et al., 1994, Operating Characteristics of 18 Different Continuous-Flow Jet Nebulizers with Beclomethasone Dipropionate Liposome Aerosol. Chest, 105(1): 106-110.

Alvine GF, Rodgers P, Fitzsimmons KM, et al., 1992, Disposable jet Nebulizers. How Reliable Are They?. Chest, 101(2): 316-319.

Massey DG, Miyauchi D, Fournier-Massey G, 1982, Nebulizer Function. Bull Eur Physiopathol Respir, 18(4): 665-671.

Fink J, Schmidt D, Power J, 2001, Comparison of a Nebulizer Using a Novel Aerosol Generator with a Standard Ultrasonic Nebulizer Designed for Use During Mechanical Ventilation. Am J Respir Crit Care Med, 163: A127.

Smith EC, Denyer J, Kendrick AH, 1995, Comparison of Twenty Three Nebulizer/Compressor Combinations for Domiciliary Use. Eur Respir J, 8(7): 1214-1221.

Dhand R, 2002, Nebulizers that Use a Vibrating Mesh or Plate with Multiple Apertures to Generate Aerosol. Respir Care, 47(12): 1406-1416.

Fink J, Barraza P, Bisgaard J, 2001, Aerosol Delivery During Mechanical Ventilation with High Frequency Oscillation: An In Vitro Evaluation. Chest, 120: 277S.

Fink JB, Schmidt D, 2002, In Vitro Comparison of Nebulizers for Aerosol Delivery during Mechanical Ventilation. Am J Respir Crit Care Med, 165: A375.

Ari A, Areabi H, Fink JB, 2010, Evaluation of Aerosol Generator Devices at 3 Locations in Humidified and Non-Humidified Circuits During Adult Mechanical Ventilation. Respir Care, 55(7): 837-844.

Fink J, Uster P, Schmidt D, et al., 2001, In Vitro Characteristics of the Aeroneb Portable Nebulizer System. J Aerosol Med, 14(3): 1-11.

Labiris NR, Dolovich MB, 2003, Pulmonary Drug Delivery. Part I: Physiological Factors Affecting Therapeutic Effectiveness of Aerosolized Medications. Br J Clin Pharmacol, 56(6): 588-599. DOI: 10.1046/j.1365-2125.2003.01892.x

Ruffin RE, Kenworthy MC, Newhouse MT, 1978, Response of Asthmatic Patients to Fenoterol Inhalation: A Method of Quantifying the Airway Bronchodilator Dose. Clin Pharmacol Ther, 23(3): 338-345.

Heyder J, Gebhart J, Rudolf G, et al., 1986, Deposition of Particles in the Human Respiratory Tract in the Size Range 0, 005-15 µm. J Aerosol Sci, 17(5): 811-825.

Abdelrahim ME, Saeed H, Harb HS, et al., 2021, Essentials of Aerosol Therapy in Critically Ill Patients, Springer.

Molina MJ, Rowland FS, 1974, Stratospheric Sink for Chlorofluoromethanes: Chlorine Atomc-Atalysed Destruction of Ozone. Nature, 249(5460): 810-812.

United Nations, 2000, The Montreal Protocol on Substances That Deplete the Ozone Layer. UN Environment Programme.,Th e%20Montreal%20Protocol%20on%20Substances%20that%20Deplete%20the%20Ozone%20Layer,consumption%20of%20ozone%2Ddepleting%20substances (accessed on September 13, 2005).

Crompton GK, 2004, How to Achieve Good Compliance with Inhaled Asthma Therapy. Respir Med, 98(Supplement 2): S35-S40.

Crompton GK, 1982, Problems Patients Have Using Pressurized Aerosol Inhalers. Eur J Respir Dis Suppl, 119: 101-104.

Allen SC, Prior A, 1986, What Determines Whether An Elderly Patient Can Use a Metered Dose Inhaler Correctly?. Br J Dis Chest, 80(1): 45-49.

Al-Showair RAM, Pearson SB, Chrystyn H, 2007, The Potential of a 2Tone Trainer to Help Patients Use Their Metered Dose Inhalers. Chest, 131(6): 1776-1782.

Tomlinson HS, Corlett SA, Allen MB, et al., 2005, Assessment of Different Methods of Inhalation from Salbutamol Metered Dose Inhalers by Urinary Drug Excretion and Methacholine Challenge. Br J Clin Pharmacol, 60(6): 605-610.

Pedersen S, Mortensen S, 1990, Use of Different Inhalation Devices in Children. Lung, 168: 653-657.

Newman SP, Weisz AW, Talaee N, et al., 1991, Improvement of Drug Delivery with a Breath Actuated Pressurised Aerosol for Patients with Poor Inhaler Technique. Thorax, 46(10): 712-716.

Hardy JG, Jausja AK, Frier M, et al., 1996, A Small Volume Spacer for Use with a Breath-Operated Pressurised Metered Dose Inhaler. Int J Pharm, 142(1): 129-133.

Newman SP, Clarke SW, 1993, Bronchodilator Delivery from Gentlehaler, A New Low-Velocity Pressurized Aerosol Inhaler. Chest, 103(5): 1442-1446.

Shrewsbury SB, Mohsen NM, Newman SP, et al., 2006, Novel Pressurised Metered Dose Inhaler Aerosol Delivery of Fluticasone Propionate via Tempo(R) in Humans. J Allergy Clin Immunol, 117(2, Supplement 1): S91.

Newnham DM, McDevitt DG, Lipworth BJ, 1993, Comparison of the Extrapulmonary Beta2-Adrenoceptor Responses and Pharmacokinetics of Salbutamol Given by Standard Metered Dose-Inhaler and Modified Actuator Device. Br J Clin Pharmacol, 36(5): 445-50.

Terzano C, Mannino F, 1999, Aerosol Characterization of Three Corticosteroid Metered Dose Inhalers with Volumatic Holding Chambers and Metered Dose Inhalers Alone at Two Inspiratory Flow Rates. J Aerosol Med, 12(4): 249-254.

British Thoracic Society, Scottish Intercollegiate Guidelines Network, 2007, British Guideline on the Management of Asthma. Thorax, 69 Suppl 1: 1-98.

O’Callaghan C, Lynch J, Cant M, et al., 1993, Improvement in Sodium Cromoglycate Delivery from a Spacer Device by Use of an Antistatic Lining, Immediate Inhalation, and Avoiding Multiple Actuations of Drug. Thorax, 48(6): 603-606.

Bisgaard H, 1995, A Metal Aerosol Holding Chamber Devised for Young Children with Asthma. Eur Respir J, 8(5): 856-860.

Bisgaard H, 1997, Delivery of Inhaled Medication to Children. J Asthma, 34(6): 443-467.

Cates C, 2003, Spacers and Nebulisers for the Delivery of Beta-Agonists in Non-Life-Threatening Acute Asthma. Respir Med, 97(7): 762-769.

Dhand R, Tobin MJ, 1996, Bronchodilator Delivery with Metered-Dose Inhalers in Mechanically-Ventilated Patients. Eur Respir J, 9(3): 585-595.

Manthous CA, Chatila W, Schmidt GA, et al., 1995, Treatment of Bronchospasm by Metered-Dose Inhaler Albuterol in Mechanically Ventilated Patients. Chest, 107(1): 210-213.

Barry PW, O’Callaghan C, 1994, Multiple Actuations of Salbutamol MDI into a Spacer Device Reduce the Amount of Drug Recovered in the Respirable Range. Eur Respir J, 7(9): 1707-1709.

Barry PW, O’Callaghan C, 2003, The Influence of Inhaler Selection on Efficacy of Asthma Therapies. Adv Drug Deliv Rev, 55(7): 879-923.

Barry P, O’Callaghan C, 1996, Inhalational Drug Delivery from Seven Different Spacer Devices. Thorax, 51(8): 835-840.

Newman S, 2004, Spacer Devices for Metered Dose Inhalers. Clin Pharmacokinet, 43(6): 349-360.

Comis A, Valletta EA, Sette L, et al., 1993, Comparison of Nedocromil Sodium and Sodium Cromoglycate Administered by Pressurized Aerosol, with and Without a Spacer Device in Exercise-Induced Asthma in Children. Eur Respir J, 6(4): 523-526.

Castro-Rodriguez JA, Rodrigo GJ, 2004, ß-Agonists Through Metered-Dose Inhaler with Valved Holding Chamber Versus Nebulizer for Acute Exacerbation of Wheezing or Asthma in Children Under 5 Years of Age: A Systematic Review with Meta-Analysis. J Pediatr, 145(2): 172-177.

Gleeson JG, Price JF, 1988, Nebuhaler Technique. Br J Dis Chest, 82(2): 172-174.

Kraemer R, 1995, Babyhaler – A New Paediatric Aerosol Device. J Aerosol Med, 8(2): S19-S26.

O’Callaghan C, Barry PW, 2000, How to Choose Delivery Devices for Asthma. Arch Dis Child, 82(3): 185-187.

Fok TF, Lam K, Ng PC, et al., 1998, Delivery of Salbutamol to Nonventilated Preterm Infants by Metered-Dose Inhaler, Jet Nebulizer, and Ultrasonic Nebulizer. Eur Respir J, 12(1): 159-164.

de Boer AH, Gjaltema D, Hagedoorn P, 1996, Inhalation Characteristics and Their Effects on In Vitro Drug Delivery from Dry Powder Inhalers Part 2: Effect of Peak Flow Rate (PIFR) and Inspiration Time on the In Vitro Drug Release from Three Different Types of Commercial Dry Powder Inhalers. Int J Pharm, 138(1): 45-56.

Chrystyn H, 2006, Closer to an “Ideal Inhaler” with the Easyhaler: An Innovative Dry Powder Inhaler. Clin Drug Investig, 26(4): 175-183.

Kohler D, 2004, The Novolizer: Overcoming Inherent Problems of Dry Powder Inhalers. Respir Med, 98(Supplement 1): S17-S21.

Richter K, 2004, Successful Use of DPI Systems in Asthmatic Patients – Key Parameters. Respir Med, 98(Supplement 2): S22-S27.

Cegla UH, 2004, Pressure and Inspiratory Flow Characteristics of Dry Powder Inhalers. Respir Med, 98(Supplement 1): S22-S28.

Chrystyn H, 1999, The Diskus Inhaler. Clin Drug Investig, 18(4): 287-296.

Clark AR, Hollingworth AM, 1993, The Relationship Between Powder Inhaler Resistance and Peak Inspiratory Conditions in Healthy Volunteers – Implications for In Vitro Testing. J Aerosol Med, 6(2): 99-110.

Chrystyn H, 2003, Is Inhalation Rate Important for a Dry Powder Inhaler? Using the In-Check Dial to Identify These Rates. Respir Med, 97(2): 181-187.

de Boer AH, Winter HMI, Lerk CF, et al., 1997, Inhalation Characteristics and Their Effects on In Vitro Drug Delivery from Dry Powder Inhalers: Part 3: The Effect of Flow Increase Rate (FIR) on the In Vitro Drug Release from the Pulmicort 200 Turbuhaler. Int J Pharm, 153(1): 67-77.

Miller NC, Maniaci MJ, Dwivedi SK, et al., 2000, Aerodynamic Sizing with Simulated Inhalation Profiles: Total Dose Capture and Measurement. Resp Drug Deliv VII, 1: 191-196.

Palander A, Mattila T, Karhu M, et al., 2000, In Vitro Comparison of Three Salbutamol-Containing Multidose Dry Powder Inhalers: Buventol Easyhaler, Inspiryl Turbuhaler and Ventoline Diskus. Clin Drug Investig, 20(1): 25-33.

Gustafsson P, Taylor A, Zanen P, et al., 2005, Can Patients Use All Dry Powder Inhalers Equally Well?. Int J Clin Pract, 59(s149): 13-18.

Chrystyn H, 2005, Do Patients Show the Same Level of Adherence with All Dry Powder Inhalers?. Int J Clin Pract, 59(Suppl 149): 19-25.

Williams AE, Chrystyn H, 2007, Survey of Pharmacists’ Attitudes Towards Interchangeable Use of Dry Powder Inhalers. Pharm World Sci, 29(3): 221-227.

Ashurst I, Malton A, Prime D, et al., 2000, Latest Advances in the Development of Dry Powder Inhalers. PSTT, 3(7): 246-256.

Tarsin W, Corrado OJ, Brownlee K, et al., 2001, Inter-Individual Variability of Peak Inhalation Rate Through Different Inhalers by Asthmatic Children and Adults and Those with COPD. Eur Respir J, 18(Suppl 33): 133S.

Pedersen S, Hansen OR, Fuglsang G, 1990, Influence of Inspiratory Flow Rate Upon the Effect of a Turbuhaler. Arch Dis Child, 65(3): 308-310.