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Drug Delivery Devices for Inhaled Medicines

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Pharmacology and Therapeutics of Asthma and COPD

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 237))

Abstract

Historically, the inhaled route has been used for the delivery of locally-acting drugs for the treatment of respiratory conditions, such as asthma, COPD, and airway infections. Targeted delivery of substances to the lungs has some key advantages over systemic administration, including a more rapid onset of action, an increased therapeutic effect, and, depending on the agent inhaled, reduced systemic side effects since the required local concentration in the lungs can be obtained with a lower dose. Fortunately, when designed properly, inhaled drug delivery devices can be very effective and safe for getting active agents directly to their site of action.

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References

  • Albasarah YY, Somavarapu S, Taylor KMG (2010) Stabilizing protein formulations during air-jet nebulization. Int J Pharm 402(1–2):140–145

    Article  CAS  PubMed  Google Scholar 

  • Amini MA, Faramarzi MA, Gilani K, Moazeni E, Esmaeilzadeh-Gharehdaghi E, Amani A (2014) Production, characterisation, and in vitro nebulisation performance of budesonide-loaded PLA nanoparticles. J Microencapsul 64:1–7

    Google Scholar 

  • Auerbach O, Stout AP, Hammond EC, Garfinkel L (1966) Emphysema and other pulmonary changes in smokers. Postgrad Med 40(1):95–100

    Article  CAS  PubMed  Google Scholar 

  • Aurora SK, Silberstein SD, Kori SH, Tepper SJ, Borland SW, Wang M et al (2011) MAP0004, orally inhaled DHE: a randomized, controlled study in the acute treatment of migraine. Headache 51(4):507–517

    Article  PubMed  Google Scholar 

  • Barnes N, Price D, Colice G, Chisholm A, Dorinsky P, Hillyer EV et al (2011) Asthma control with extrafine-particle hydrofluoroalkane-beclometasone vs. large-particle chlorofluorocarbon-beclometasone: a real-world observational study. Clin Exp Allergy 41(11):1521–1532

    Article  CAS  PubMed  Google Scholar 

  • Bell J, Newman S (2007) The rejuvenated pressurised metered dose inhaler. Expert Opin Drug Deliv 4(3):215–234

    Article  CAS  PubMed  Google Scholar 

  • Bennett WD (2005) Controlled inhalation of aerosolised therapeutics. Expert Opin Drug Deliv 2(4):763–767

    Article  CAS  PubMed  Google Scholar 

  • Bennett WD, Smaldone GC (1987) Human variation in the peripheral air-space deposition of inhaled particles. J Appl Physiol 62(4):1603–1610

    CAS  PubMed  Google Scholar 

  • Bisgaard H, Anhoj J, Wildhaber JH (2002) Spacer devices. In: Bisgaard H, O’Callaghan C, Smaldone GC (eds) Drug delivery to the lung. p 511

    Google Scholar 

  • Bosquillon C, Préat V, Vanbever R (2004) Pulmonary delivery of growth hormone using dry powders and visualization of its local fate in rats. J Control Release 96(2):233–244

    Article  CAS  PubMed  Google Scholar 

  • Brocklebank D, Ram F, Wright J, Barry P, Cates C, Davies L et al (2001) Comparison of the effectiveness of inhaler devices in asthma and chronic obstructive airways disease: a systematic review of the literature. Health Technol Assess 5(26)

    Google Scholar 

  • Broeders MEAC, Sanchis J, Levy ML, Crompton GK, Dekhuijzen PNR (2009) The ADMIT series--issues in inhalation therapy. 2. Improving technique and clinical effectiveness. Prim Care Respir J 18(2):76–82

    Article  PubMed  Google Scholar 

  • Cazzola M, Page CP, Calzetta L, Matera MG (2012) Pharmacology and therapeutics of bronchodilators. Pharmacol Rev 64(3):450–504

    Article  CAS  PubMed  Google Scholar 

  • Coates AL, MacNeish CF, Meisner D, Kelemen S, Thibert R, MacDonald J et al (1997) The choice of jet nebulizer, nebulizing flow, and addition of albuterol affects the output of tobramycin aerosols. Chest 111(5):1206–1212

    Article  CAS  PubMed  Google Scholar 

  • Cochrane MG, Bala MV, Downs KE, Mauskopf J, Ben-Joseph RH (2000) Inhaled corticosteroids for asthma therapy: patient compliance, devices, and inhalation technique. Chest 117(2):542–550

    Article  CAS  PubMed  Google Scholar 

  • Cornfield J, Haenszel W, Hammond E, Lilienfield A, Shimkin M, Wynder E (1959) Smoking and lung cancer - recent evidence and a discussion of some questions. J Natl Cancer Inst 22:173–203

    CAS  PubMed  Google Scholar 

  • Cornfield J, Haenszel W, Hammond EC, Lilienfeld AM, Shimkin MB, Wynder EL (2009) Smoking and lung cancer: recent evidence and a discussion of some questions. Int J Epidemiol 38(5):1175–1191

    Article  PubMed  Google Scholar 

  • Dalby R, Spallek M, Voshaar T (2004) A review of the development of Respimat Soft Mist Inhaler. Int J Pharm 283(1–2):1–9

    Article  CAS  PubMed  Google Scholar 

  • de Boer AH, Hagedoorn P, Frijlink HW (2003) The choice of a compressor for the aerosolisation of tobramycin (TOBI®) with the PARI LC PLUS® reusable nebuliser. Int J Pharm 268(1–2):59–69

    Article  PubMed  Google Scholar 

  • Dolovich MB, Ahrens RC, Hess DR, Anderson P, Dhand R, Rau JL et al (2005) Device selection and outcomes of aerosol therapy: evidence-based guidelines. Chest 335–371

    Google Scholar 

  • Elhissi AMA, Karnam KK, Danesh-Azari M-R, Gill HS, Taylor KMG (2006) Formulations generated from ethanol-based proliposomes for delivery via medical nebulizers. J Pharm Pharmacol 58(7):887–894

    Article  CAS  PubMed  Google Scholar 

  • Elhissi AMA, Faizi M, Naji WF, Gill HS, Taylor KMG (2007) Physical stability and aerosol properties of liposomes delivered using an air-jet nebulizer and a novel micropump device with large mesh apertures. Int J Pharm 334(1–2):62–70

    Article  CAS  PubMed  Google Scholar 

  • European Medicines Agency (2012) Guideline on good pharmacovigilance practices (GVP) Module VI – Management and reporting of adverse reactions to medicinal. p 90

    Google Scholar 

  • Farr SJ, Otulana BA (2006) Pulmonary delivery of opioids as pain therapeutics. Adv Drug Deliv Rev 58(9–10):1076–1088

    Article  CAS  PubMed  Google Scholar 

  • Fischer A, Stegemann J, Scheuch G, Siekmeier R (2009) Novel devices for individualized controlled inhalation can optimize aerosol therapy in efficacy, patient care and power of clinical trials. Eur J Med Res 14(Suppl 4):71–77

    Article  PubMed  PubMed Central  Google Scholar 

  • Fonseca DE, Kline JN (2009) Use of CpG oligonucleotides in treatment of asthma and allergic disease. Adv Drug Deliv Rev 61(3):256–262

    Article  CAS  PubMed  Google Scholar 

  • Frijlink H, De Boer A (2004) Dry powder inhalers for pulmonary drug delivery. Expert Opin Drug Deliv 1(1):67–86

    Article  CAS  PubMed  Google Scholar 

  • Fulda G, Giberson F, Fagraeus L (2005) A prospective randomized trial of nebulized morphine compared with patient-controlled analgesia morphine in the management of acute thoracic pain. J Trauma 59(2):383–388

    Article  CAS  PubMed  Google Scholar 

  • Furyk JS, Grabowski WJ, Black LH (2009) Nebulized fentanyl versus intravenous morphine in children with suspected limb fractures in the emergency department: a randomized controlled trial. Emerg Med Australas 21(3):203–209

    Article  PubMed  Google Scholar 

  • Gabrio BJ, Stein SW, Velasquez DJ (1999) A new method to evaluate plume characteristics of hydrofluoroalkane and chlorofluorocarbon metered dose inhalers. Int J Pharm 186(1):3–12

    Article  CAS  PubMed  Google Scholar 

  • Geller DE, Kesser KC (2010) The I-neb Adaptive Aerosol Delivery System enhances delivery of alpha1-antitrypsin with controlled inhalation. J Aerosol Med Pulm Drug Deliv 23(Suppl 1):S55–S59

    CAS  PubMed  Google Scholar 

  • Giraud V, Roche N (2002) Misuse of corticosteroid metered-dose inhaler is associated with decreased asthma stability. Eur Respir J 19(2):246–251

    Article  CAS  PubMed  Google Scholar 

  • Goldin JG, Tashkin DP, Kleerup EC, Greaser LE, Haywood UM, Sayre JW et al (1999) Comparative effects of hydrofluoroalkane and chlorofluorocarbon beclomethasone dipropionate inhalation on small airways: assessment with functional helical thin-section computed tomography. J Allergy Clin Immunol 104(6):S258–S267

    Article  CAS  PubMed  Google Scholar 

  • Heinemann L, Klappoth W, Rave K, Hompesch B, Linkeschowa R, Heise T (2000) Intra-individual variability of the metabolic effect of inhaled insulin together with an absorption enhancer. Diabetes Care 23(9):1343–1347

    Article  CAS  PubMed  Google Scholar 

  • Hertel S, Pohl T, Friess W, Winter G (2014) Prediction of protein degradation during vibrating mesh nebulization via a high throughput screening method. Eur J Pharm Biopharm 87(2):386–394

    Article  CAS  PubMed  Google Scholar 

  • Hinds W (1982) Aerosol technology: properties, behavior, and measurement of airborne particles. Wiley-Interscience, New York, 442 pp

    Google Scholar 

  • Khatri L, Taylor KM, Craig DQ, Palin K (2001) An assessment of jet and ultrasonic nebulisers for the delivery of lactate dehydrogenase solutions. Int J Pharm 227(1–2):121–131

    Article  CAS  PubMed  Google Scholar 

  • Kleemann E, Schmehl T, Gessler T, Bakowsky U, Kissel T, Seeger W (2007) Iloprost-containing liposomes for aerosol application in pulmonary arterial hypertension: formulation aspects and stability. Pharm Res 24(2):277–287

    Article  CAS  PubMed  Google Scholar 

  • Larche M (2014) Mechanisms of peptide immunotherapy in allergic airways disease. Ann Am Thorac Soc 11:S292–S296

    Article  PubMed  Google Scholar 

  • Laube B, Georgopoulos A, Adams G (1998) Preliminary study of the efficacy of insulin aerosol delivered by oral inhalation in diabetic patients. J Am Med Assoc 269:2106–2109

    Article  Google Scholar 

  • Laube BL, Janssens HM, de Jongh FHC, Devadason SG, Dhand R, Diot P et al (2011) What the pulmonary specialist should know about the new inhalation therapies. Eur Respir J 37(6):1308–1331

    Article  CAS  PubMed  Google Scholar 

  • Lavorini F (2013) The challenge of delivering therapeutic aerosols to asthma patients. ISRN Allergy 102418

    Google Scholar 

  • Lavorini F, Magnan A, Dubus JC, Voshaar T, Corbetta L, Broeders M et al (2008) Effect of incorrect use of dry powder inhalers on management of patients with asthma and COPD. Respir Med 102(4):593–604

    Article  PubMed  Google Scholar 

  • Le Brun PP, de Boer AH, Gjaltema D, Hagedoorn P, Heijerman HG, Frijlink HW (1999) Inhalation of tobramycin in cystic fibrosis. Part 2: optimization of the tobramycin solution for a jet and an ultrasonic nebulizer. Int J Pharm 189(2):215–225

    Article  PubMed  Google Scholar 

  • Le Brun PP, de Boer AH, Heijerman HG, Frijlink HW (2000) A review of the technical aspects of drug nebulization. Pharm World Sci 22(3):75–81

    Article  PubMed  Google Scholar 

  • Leach C (1998) Improved delivery of inhaled steroids to the large and small airways. Respir Med 92(Suppl):3–8

    Article  PubMed  Google Scholar 

  • Leach CL, Davidson PJ, Hasselquist BE, Boudreau RJ (2002) Lung deposition of hydrofluoroalkane-134a beclomethasone is greater than that of chlorofluorocarbon fluticasone and chlorofluorocarbon beclomethasone: a cross-over study in healthy volunteers. Chest 122(2):510–516

    Article  CAS  PubMed  Google Scholar 

  • Lexmond AJ, Hagedoorn P, Frijlink HW, de Boer AH (2013) Challenging the two-minute tidal breathing challenge test. J Aerosol Med Pulm Drug Deliv 26:1–7

    Article  Google Scholar 

  • Lexmond AJ, Kruizinga TJ, Hagedoorn P, Rottier BL, Frijlink HW, De Boer AH (2014a) Effect of inhaler design variables on paediatric use of dry powder inhalers. PLoS One 9(6), e99304

    Article  PubMed  PubMed Central  Google Scholar 

  • Lexmond AJ, Hagedoorn P, van der Wiel E, ten Hacken NHT, Frijlink HW, de Boer AH (2014b) Adenosine dry powder inhalation for bronchial challenge testing, part 1: inhaler and formulation development and in vitro performance testing. Eur J Pharm Biopharm 86(1):105–114

    Article  CAS  PubMed  Google Scholar 

  • Lexmond AJ, van der Wiel E, Hagedoorn P, Bult W, Frijlink HW, ten Hacken NHT et al (2014c) Adenosine dry powder inhalation for bronchial challenge testing, part 2: proof of concept in asthmatic subjects. Eur J Pharm Biopharm 88:148–152

    Article  CAS  PubMed  Google Scholar 

  • Lizio R, Klenner T, Borchard G, Romeis P, Sarlikiotis AW, Reissmann T et al (2000) Systemic delivery of the GnRH antagonist cetrorelix by intratracheal instillation in anesthetized rats. Eur J Pharm Sci 9(3):253–258

    Article  CAS  PubMed  Google Scholar 

  • MacNeish CF, Coates AL, Meisner D, Thibert R, Kelemen S, Vadas EB (1997) A comparison of pulmonary availability between Ventolin (albuterol) nebules and Ventolin (albuterol) respirator solution. Chest 111(1):204–208

    Article  CAS  PubMed  Google Scholar 

  • Máiz L, Lamas A, Fernández-Olmos A, Suárez L, Cantón R (2009) Unorthodox long-term aerosolized ampicillin use for methicillin-susceptible Staphylococcus aureus lung infection in a cystic fibrosis patient. Pediatr Pulmonol 44(5):512–515

    Article  PubMed  Google Scholar 

  • McCallion ONM, Taylor KMG, Thomas M, Taylor AJ (1995) Nebulization of fluids of different physicochemical properties with air-jet and ultrasonic nebulizers. Pharm Res 12(11):1682–1688

    Article  CAS  PubMed  Google Scholar 

  • McCormack P, Southern KW, McNamara PS (2012) New nebulizer technology to monitor adherence and nebulizer performance in cystic fibrosis. J Aerosol Med Pulm Drug Deliv 25(6):307–309

    Article  CAS  PubMed  Google Scholar 

  • Melani AS, Canessa P, Coloretti I, DeAngelis G, DeTullio R, Del Donno M et al (2012) Inhaler mishandling is very common in patients with chronic airflow obstruction and long-term home nebuliser use. Respir Med 106(5):668–676

    Article  PubMed  Google Scholar 

  • Mishra NC, Rir-sima-ah J, Langley RJ, Singh SP, Pena-Philippides JC, Koga T et al (2008) Nicotine primarily suppresses lung Th2 but not goblet cell and muscle cell responses to allergens. J Immunol 180(11):7655–7663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Münster AB, Bendstrup E, Jensen JI, Gram J (2000) Jet and ultrasonic nebulization of single chain urokinase plasminogen activator (scu-PA). J Aerosol Med 13(4):325–333

    Article  PubMed  Google Scholar 

  • Newhouse M, Dolovich M (1986) Control of asthma by aerosols. N Engl J Med 315:870–874

    Article  CAS  PubMed  Google Scholar 

  • Newman SP, Pellow PGD, Clarke SW (1986) Droplet size distributions of nebulised aerosols for inhalation therapy. Clin Phys Physiol Meas 7(2):139–146

    Article  CAS  PubMed  Google Scholar 

  • Nikander K, Prince I, Coughlin S, Warren S, Taylor G (2010) Mode of breathing – tidal or slow and deep – through the I-neb Adaptive Aerosol Delivery (AAD) System. J Aerosol Med Pulm Drug Deliv 23(Suppl 1):S37–S43

    CAS  PubMed  Google Scholar 

  • Niven RW, Brain JD (1994) Some functional aspects of air-jet nebulizers. Int J Pharm 104(1):73–85

    Article  Google Scholar 

  • O’Byrne PM (2013) Role of monoclonal antibodies in the treatment of asthma. Can Respir J 20(1):23–25

    Article  PubMed  PubMed Central  Google Scholar 

  • Otterson GA, Villalona-Calero MA, Hicks W, Pan X, Ellerton JA, Gettinger SN et al (2010) Phase I/II study of inhaled doxorubicin combined with platinum-based therapy for advanced non-small cell lung cancer. Clin Cancer Res 16(8):2466–2473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Papi A, Haughney J, Virchow JC, Roche N, Palkonen S, Price D (2011) Inhaler devices for asthma: a call for action in a neglected field. Eur Respir J 37(5):982–985

    Article  CAS  PubMed  Google Scholar 

  • Patton JS, Byron PR (2007) Inhaling medicines: delivering drugs to the body through the lungs. Nat Rev Drug Discov 6(1):67–74

    Article  CAS  PubMed  Google Scholar 

  • Pedersen S, Dubus JC, Crompton GK (2010) The ADMIT series--issues in inhalation therapy. 5) Inhaler selection in children with asthma. Prim Care Respir J 19(3):209–216

    Article  PubMed  Google Scholar 

  • Price D, Chrystyn H, Kaplan A, Haughney J, Román-Rodríguez M, Burden A et al (2012) Effectiveness of same versus mixed asthma inhaler devices: a retrospective observational study in primary care. Allergy Asthma Immunol Res 4(4):184–191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Price D, Bosnic-Anticevich S, Briggs A, Chrystyn H, Rand C, Scheuch G et al (2013) Inhaler competence in asthma: common errors, barriers to use and recommended solutions. Respir Med 107(1):37–46

    Article  CAS  PubMed  Google Scholar 

  • Rottier BL, van Erp CJP, Sluyter TS, Heijerman HGM, Frijlink HW, De Boer AH (2009) Changes in performance of the Pari eFlow rapid and Pari LC Plus during 6 months use by CF patients. J Aerosol Med Pulm Drug Deliv 22(3):263–269

    Article  PubMed  Google Scholar 

  • Salter H (1868) On asthma; its pathology and treatment. Philadelphia

    Google Scholar 

  • Self TH, Arnold LB, Czosnowski LM, Swanson JM, Swanson H (2007) Inadequate skill of healthcare professionals in using asthma inhalation devices. J Asthma 44(8):593–598

    Article  PubMed  Google Scholar 

  • Siekmeier R, Scheuch G (2008) Systemic treatment by inhalation of macromolecules–principles, problems, and examples. J Physiol Pharmacol 53–79

    Google Scholar 

  • Silberstein S (2012) MAP0004: dihydroergotamine mesylate inhalation aerosol for acute treatment of migraine. Expert Opin Pharmacother 13(13):1961–1968

    Article  CAS  PubMed  Google Scholar 

  • Smyth H (2005) Propellant-driven metered-dose inhalers for pulmonary drug delivery. Expert Opin Drug Deliv 2(1):53–74

    Article  PubMed  Google Scholar 

  • U.S. Department of Health and Human Services (2010) How tobacco smoke causes disease: the biology and behavioral basis for smoking-attributable disease. A report of the Surgeon General. Centers for Disease Control and Prevention (US), Atlanta (GA). 7, Pulmonary Diseases. 704 pp

    Google Scholar 

  • van der Palen J, Klein JJ, van Herwaarden CL, Zielhuis GA, Seydel ER (1999) Multiple inhalers confuse asthma patients. Eur Respir J 14(5):1034–1037

    Article  PubMed  Google Scholar 

  • Wauthoz N, Deleuze P, Hecq J, Roland I, Saussez S, Adanja I et al (2010) In vivo assessment of temozolomide local delivery for lung cancer inhalation therapy. Eur J Pharm Sci 39(5):402–411

    Article  CAS  PubMed  Google Scholar 

  • Weibel ER (1963) Morphometry of the human lung. Springer-Verlag, 151 pp

    Google Scholar 

  • Xu X, Wang X, Ge W, Pan L, Zheng M (2012) The pharmacokinetics of inhaled morphine delivered by an ultrasonic nebulizer in ventilated dogs. J Aerosol Med Pulm Drug Deliv 25(1):41–46

    Article  CAS  PubMed  Google Scholar 

  • Zheng Y, Marsh KC, Bertz RJ, El-Shourbagy T, Adjei AL (1999) Pulmonary delivery of a dopamine D-1 agonist, ABT-431, in dogs and humans. Int J Pharm 191(2):131–140

    Article  CAS  PubMed  Google Scholar 

  • Zijlstra GS, Hinrichs WLJ, de Boer AH, Frijlink HW (2004) The role of particle engineering in relation to formulation and de-agglomeration principle in the development of a dry powder formulation for inhalation of cetrorelix. Eur J Pharm Sci 23(2):139–149

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. King’s College London, London, SEI 9NH, UK

    Anne Lexmond & Ben Forbes

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  1. Anne Lexmond
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  2. Ben Forbes
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Correspondence to Ben Forbes .

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Editors and Affiliations

  1. Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King’s College London, London, United Kingdom

    Clive P. Page

  2. Airway Disease Section, Imperial College, National Heart and Lung Institute, London, United Kingdom

    Peter J. Barnes

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Lexmond, A., Forbes, B. (2016). Drug Delivery Devices for Inhaled Medicines. In: Page, C., Barnes, P. (eds) Pharmacology and Therapeutics of Asthma and COPD. Handbook of Experimental Pharmacology, vol 237. Springer, Cham. https://doi.org/10.1007/164_2016_67

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