INFLUENCE OF PARTICLE SIZE AND PARTICLE DEPOSITION OF INHALED MEDICATION IN LUNG DISEASE: A COMREHENSIVE REVIEW
Abstract
Drug particles less than 5 μm have the greatest probability of deposition in the lung, whereas those less than 2 μm tend to be concentrated in the alveoli. A large proportion of particles within the 2-5 μm range are present in the dose released from the inhaled drug, providing a relatively even distribution across the lungs. The efficient need for inhaled therapy highly depends on the essence of the method of drug delivery and the patient's ability to correctly use the system. A large range of inhaler products, each with positive and negative aspects, are on the market. It facilitates the administration of a lower dose; there is a quicker onset of action and less severe side effects. The deposition of the inhaled drug in the lung is dependent on particle size, inhalation technique and the type of inhaler device. Importance of particle size distribution and Particle aerodynamic diameter, Influence of environmental humidity on particle size Particle deposition in the airways, Methods to identify drug deposition in lungs, Physiological factors which affect the therapeutic efficacy of pulmonary delivery drugs. The nano and micro size particles is a mainstay of treatment for a variety of pulmonary diseases because they provide a platform to deliver drugs directly reliably and inexpensively to the disease site, thus allowing for a minimum amount of drug to be used and minimize side effects.
Keywords:
Particle size distribution, Particle deposition, Inhalation, Pulmonary DeliveryDOI
https://doi.org/10.25004/IJPSDR.2022.140119References
Nasr M, Taha I, Hathout RM. Suitability of liposomal carriers for systemic delivery of risedronate using the pulmonary route. Drug delivery. 2013;20(8):311-8.
Patil J, Sarasija S. Pulmonary drug delivery strategies: A concise, systematic review. Lung India: Official Organ of Indian Chest Society. 2012;29(1):44.
Paranjpe M, Müller-Goymann CC . Nanopar t icle-mediated pulmonary drug delivery: a review. International journal of molecular sciences. 2014;15(4):5852-73.
Gallo L, Bucalá V, Ramírez-Rigo MV. Formulation and characterization of polysaccharide microparticles for pulmonary delivery of sodium cromoglycate. AAPS PharmSciTech. 2017;18(5):1634-45.
Vyas S, Sakthivel T. Pressurized pack-based liposomes for pulmonary targeting of isoprenaline—development and characterization. Journal of microencapsulation. 1994;11(4):373-80.
De Kanter R, De Jager M, Draaisma A, Jurva J, Olinga P, Meijer D, et al. Drug-metabolizing activity of human and rat liver, lung, kidney and intestine slices. Xenobiotica. 2002;32(5):349-62.
Pacifici G, Franchi M, Bencini C, Repetti F, Di Lascio N, Muraro G. Tissue distribution of drug-metabolizing enzymes in humans. Xenobiotica. 1988;18(7):849-56.
Groneberg D, Witt C, Wagner U, Chung K, Fischer A. Fundamentals of pulmonary drug delivery. Respiratory medicine. 2003;97(4):382-7.
Moskal A, Gradoń L. Temporary and spatial deposition of aerosol particles in the upper human airways during breathing cycle. Journal of Aerosol Science. 2002;33(11):1525-39.
Lee W-H, Loo C-Y, Traini D, Young PM. Nano-and micro-based inhaled drug delivery systems for targeting alveolar macrophages. Expert opinion on drug delivery. 2015;12(6):1009-26.
Verma RK, Ibrahim M, Garcia-Contreras L. Lung anatomy and physiology and their implications for pulmonary drug delivery. Pulmonary Drug Delivery. 2015:1-18.
Weibel ER, Cournand AF, Richards DW. Morphometry of the human lung: Springer; 1963.
Yeh H-C, Schum G. Models of human lung airways and their application to inhaled particle deposition. Bulletin of mathematical biology. 1980;42(3):461-80.
Severinghaus J, Stupfel M. Alveolar dead space as an index of distribution of blood flow in pulmonary capillaries. Journal of Applied Physiology. 1957;10(3):335-48.
King R. Pulmonary surfactant. Journal of Applied Physiology. 1982;53(1):1-8.
Schürch S, Gehr P, Im Hof V, Geiser M, Green F. Surfactant displaces particles toward the epithelium in airways and alveoli. Respiration physiology. 1990;80(1):17-32.
Miller F, Mercer R, Crapo J. Lower respiratory tract structure of laboratory animals and humans: dosimetry implications. Aerosol science and technology. 1993;18(3):257-71.
Forbes B, Ehrhardt C. Human respiratory epithelial cell culture for drug delivery applications. European journal of pharmaceutics and biopharmaceutics. 2005;60(2):193-205.
Byron PR, PATTON JS. Drug delivery via the respiratory tract. Journal of Aerosol medicine. 1994;7(1):49-75.
Tronde A, Nordén B, Marchner H, Wendel AK, Lennernäs H, Bengtsson UH. Pulmonary absorption rate and bioavailability of drugs in vivo in rats: structure–absorption relationships and physicochemical profiling of inhaled drugs. Journal of pharmaceutical sciences. 2003;92(6):1216-33.
Patton JS, Byron PR. Inhaling medicines: delivering drugs to the body through the lungs. Nature reviews Drug discovery. 2007;6(1):67-74.
Nahar K, Gupta N, Gauvin R, Absar S, Patel B, Gupta V, et al. In vitro, in vivo and ex vivo models for studying particle deposition and drug absorption of inhaled pharmaceuticals. European journal of pharmaceutical sciences. 2013;49(5):805-18.
Patton JS, Fishburn CS, Weers JG. The lungs as a portal of entry for systemic drug delivery. Proceedings of the American Thoracic Society. 2004;1(4):338-44.
Olsson B, Bondesson E, Borgström L, Edsbäcker S, Eirefelt S, Ekelund K, et al. Pulmonary drug metabolism, clearance, and absorption. Controlled pulmonary drug delivery: Springer; 2011. p. 21-50.
Loira-Pastoriza C, Todoroff J, Vanbever R. Delivery strategies for sustained drug release in the lungs. Advanced drug delivery reviews. 2014;75:81-91.
Rabinowitz JD, Lloyd PM, Munzar P, Myers DJ, Cross S, Damani R, et al. Ultra-fast absorption of amorphous pure drug aerosols via deep lung inhalation. Journal of pharmaceutical sciences. 2006;95(11):2438-51.
Byron PR. Determinants of drug and polypeptide bioavailability from aerosols delivered to the lung. Advanced Drug Delivery Reviews. 1990;5(1-2):107-32.
Cryan S-A, Sivadas N, Garcia-Contreras L. In vivo animal models for drug delivery across the lung mucosal barrier. Advanced drug delivery reviews. 2007;59(11):1133-51.
Castranova V, Rabovsky J, Tucker J, Miles P. The alveolar type II epithelial cell: a multifunctional pneumocyte. Toxicology and applied pharmacology. 1988;93(3):472-83.
Renwick L, Donaldson K, Clouter A. Impairment of alveolar macrophage phagocytosis by ultrafine particles. Toxicology and applied pharmacology. 2001;172(2):119-27.
Costa A, Pinheiro M, Magalhães J, Ribeiro R, Seabra V, Reis S, et al. The formulation of nanomedicines for treating tuberculosis. Advanced drug delivery reviews. 2016;102:102-15.
Nickel S, Clerkin CG, Selo MA, Ehrhardt C. Transport mechanisms at the pulmonary mucosa: implications for drug delivery. Expert opinion on drug delivery. 2016;13(5):667-90.
Ghadiri M, Young PM, Traini D. Strategies to enhance drug absorption via nasal and pulmonary routes. Pharmaceutics. 2019;11(3):113.
Aliselo M, Al-Alak Hh, Ehrhardt C. Lung transporters and absorption mechanisms in the lungs. Inhalation Aerosols: Physical and Biological Basis for Therapy. 2019;1:413.
Bosquillon C. Drug transporters in the lung—do they play a role in the biopharmaceutics of inhaled drugs? Journal of pharmaceutical sciences. 2010;99(5):2240-55.
Selo MA, Al-Alak HH, Ehrhardt C. Lung transporters and absorption mechanisms in the lungs. Inhalation Aerosols: Physical and Biological Basis for Therapy. 2019;1:57.
Gumbleton M, Hollins AJ, Omidi Y, Campbell L, Taylor G. Targeting caveolae for vesicular drug transport. Journal of controlled release. 2003;87(1-3):139-51.
Fung KY, Fairn GD, Lee WL. Transcellular vesicular transport in epithelial and endothelial cells: Challenges and opportunities. Traffic. 2018;19(1):5-18.
Lehr C-M. Lectin-mediated drug delivery:: The second generation of bioadhesives. Journal of Controlled Release. 2000;65(1-2):19-29.
Chander A, Fisher AB. Regulation of lung surfactant secretion. American Journal of Physiology-Lung Cellular and Molecular Physiology. 1990;258(6):L241-L53.
Longo M, Bisagno A, Zasadzinski J, Bruni R, Waring A. A function of lung surfactant protein SP-B. Science. 1993;261(5120):453-6.
Bangham A, Morley C, Phillips M. The physical properties of an effective lung surfactant. Biochimica et Biophysica Acta (BBA)- Lipids and Lipid Metabolism. 1979;573(3):552-6.
Courrier H, Butz N, Vandamme TF. Pulmonary drug delivery systems: recent developments and prospects. Critical Reviews™ in Therapeutic Drug Carrier Systems. 2002;19(4-5).
Wauthoz N, Amighi K. Phospholipids in pulmonary drug delivery. European journal of lipid science and technology. 2014;116(9):1114- 28.
Madsen J, Kliem A, Tornøe I, Skjødt K, Koch C, Holmskov U. Localization of lung surfactant protein D on mucosal surfaces in human tissues. The Journal of Immunology. 2000;164(11):5866-70.
Takahashi A, Fujiwara T. Proteolipid in bovine lung surfactant: its role in surfactant function. Biochemical and biophysical research communications. 1986;135(2):527-32.
Ortiz-Collazos S, Estrada-López ED, Pedreira AA, Picciani PH, Oliveira Jr ON, Pimentel AS. Interaction of levofloxacin with lung surfactant at the air-water interface. Colloids and Surfaces B: Biointerfaces. 2017;158:689-96.
van ‘t Veen A, Gommers D, Mouton JW, Kluytmans JA, Krijt EJ, Lachmann B. Exogenous pulmonary surfactant as a drug delivering agent: influence of antibiotics on surfactant activity. British journal of pharmacology. 1996;118(3):593-8.
Bailey MM, Berkland CJ. Nanoparticle formulations in pulmonary drug delivery. Medicinal research reviews. 2009;29(1):196-212.
Evander E, Wollmer P, Jonson B, Lachmann B. Pulmonary clearance of inhaled 99mTc-DTPA: effects of surfactant depletion by lung lavage. Journal of Applied Physiology. 1987;62(4):1611-4.
Rooney SA, Young SL, Mendelson CR. Molecular and cellular processing of lung surfactant 1. The FASEB Journal. 1994;8(12):957-67.
Wiedmann TS, Bhatia R, Wattenberg L. Drug solubilization in lung surfactant. Journal of controlled release. 2000;65(1-2):43-7.
Sosnowski TR. Influence of insoluble aerosol deposits on the surface activity of the pulmonary surfactant: a possible mechanism of alveolar clearance retardation? Aerosol Science & Technology. 2000;32(1):52-60.
Ungaro F, di Villa Bianca RdE, Giovino C, Miro A, Sorrentino R, Quaglia F, et al. Insulin-loaded PLGA/cyclodextrin large porous particles with improved aerosolization properties: in vivo deposition and hypoglycaemic activity after delivery to rat lungs. Journal of Controlled Release. 2009;135(1):25-34.
Seeger W, Adir Y, Barberà JA, Champion H, Coghlan JG, Cottin V, et al. Pulmonary hypertension in chronic lung diseases. Journal of the American College of Cardiology. 2013;62(25 Supplement):D109-D16.
Faner R, Rojas M, MacNee W, Agustí A. Abnormal lung aging in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. American journal of respiratory and critical care medicine. 2012;186(4):306-13.
Chilosi M, Poletti V, Rossi A. The pathogenesis of COPD and IPF: distinct horns of the same devil? Respiratory research. 2012;13(1):1-9.
Halbert R, Natoli J, Gano A, Badamgarav E, Buist AS, Mannino D. Global burden of COPD: systematic review and meta-analysis. European Respiratory Journal. 2006;28(3):523-32.
Collaborators GCRD. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. The Lancet Respiratory Medicine. 2017;5(9):691.
Organization WH. Global Tuberculosis Report 2018 and Global Tuberculosis Report (2018) https://www. who. int/tb/publications/ global_report/en. Accessed; 2019.
Durham AL, Caramori G, Chung KF, Adcock IM. Targeted anti-inflammatory therapeutics in asthma and chronic obstructive lung disease. Translational Research. 2016;167(1):192-203.
Fujita Y, Takeshita F, Kuwano K, Ochiya T. RNAi therapeutic platforms for lung diseases. Pharmaceuticals. 2013;6(2):223-50.
Baker KE, Bonvini SJ, Donovan C, Foong RE, Han B, Jha A, et al. Novel drug targets for asthma and COPD: lessons learned from in vitro and in vivo models. Pulmonary pharmacology & therapeutics. 2014;29(2):181-98.
Lewis D, Ganderton D, Meakin B, Brambilla G, Ferraris A. Formulations containing an anticholinergic drug for the treatment of chronic obstructive pulmonary disease. Google Patents; 2005.
Adi H, Young PM, Chan H-K, Agus H, Traini D. Co-spray-dried mannitol–ciprofloxacin dry powder inhaler formulation for cystic fibrosis and chronic obstructive pulmonary disease. European journal of pharmaceutical sciences. 2010;40(3):239-47.
A l ipou r S , Mont a ser i H, Ta f ag hod i M. P r epa r at ion a nd characterization of biodegradable paclitaxel loaded alginate microparticles for pulmonary delivery. Colloids and Surfaces B: Biointerfaces. 2010;81(2):521-9.
L e o n a r d S A , J o h n s o n K A . N e b u l i z e r f o r mu l a t i o n s o f dehydroepiandrosterone and methods of treating asthma or chronic obstructive pulmonary disease using compositions thereof. Google Patents; 2008.
Vartiainen V, Raula J, Koli K, Myllärniemi M, editors. Development of Inhalable Drug Formulations for Idiopathic Pulmonary Fibrosis. Journal Of Aerosol Medicine And Pulmonary Drug Delivery; 2017: Mary Ann Liebert, Inc 140 Huguenot Street, 3rd Fl, New Rochelle, NY 10801 USA.
Gill KK, Nazzal S, Kaddoumi A. Paclitaxel loaded PEG5000– DSPE micelles as pulmonary delivery platform: formulation characterization, tissue distribution, plasma pharmacokinetics, and toxicological evaluation. European Journal of Pharmaceutics and Biopharmaceutics. 2011;79(2):276-84.
Pilcer G, Sebti T, Amighi K. Formulation and characterization of lipid-coated tobramycin particles for dry powder inhalation. Pharmaceutical research. 2006;23(5):931-40.
Chougule M, Padhi B, Misra A. Nano-liposomal dry powder inhaler of tacrolimus: preparation, characterization, and pulmonary pharmacokinetics. International journal of nanomedicine. 2007;2(4):675.
Naikwade SR, Bajaj AN, Gurav P, Gatne MM, Soni PS. Development of budesonide microparticles using spray-drying technology for pulmonary administration: design, characterization, in vitro evaluation, and in vivo efficacy study. Aaps Pharmscitech. 2009;10(3):993-1012.
Lee SH, Teo J, Heng D, Ng WK, Chan H-K, Tan RB. Synergistic combination dry powders for inhaled antimicrobial therapy: formulation, characterization and in vitro evaluation. European Journal of Pharmaceutics and Biopharmaceutics. 2013;83(2):275-84.
Steiner SS, Feldstein R, Lian H, Rhodes CA, Shen GS. Method for drug delivery to the pulmonary system. Google Patents; 2013.
Jaspart S, Bertholet P, Piel G, Dogné J-M, Delattre L, Evrard B. Solid lipid microparticles as a sustained release system for pulmonary drug delivery. European journal of pharmaceutics and biopharmaceutics. 2007;65(1):47-56.
Chow AH, Tong HH, Chattopadhyay P, Shekunov BY. Particle engineering for pulmonary drug delivery. Pharmaceutical research. 2007;24(3):411-37.
Hanes J, Edwards DA, Evora C, Langer R. Particles incorporating surfactants for pulmonary drug delivery. Google Patents; 1999.
Lipworth BJ. Pharmacokinetics of inhaled drugs. British journal of clinical pharmacology. 1996;42(6):697-705.
Newman S, Steed K, Hooper G, Källén A, Borgström L. Comparison of gamma scintigraphy and a pharmacokinetic technique for assessing pulmonary deposition of terbutaline sulphate delivered by pressurized metered dose inhaler. Pharmaceutical research. 1995;12(2):231-6.
Saari S, Vidgren M, Herrala J, Turjanmaa V, Koskinen M, Nieminen M. Possibilities of formoterol to enhance the peripheral lung deposition of the inhaled liposome corticosteroids. Respiratory medicine. 2002;96(12):999-1005.
Emmett P, Aitken R, Hannan W. Measurements of the total and regional deposition of inhaled particles in the human respiratory tract. Journal of Aerosol Science. 1982;13(6):549-60.
Alföldy B, Giechaskiel B, Hofmann W, Drossinos Y. Size-distribution dependent lung deposition of diesel exhaust particles. Journal of Aerosol Science. 2009;40(8):652-63.
Trivedi R, Redente EF, Thakur A, Riches DW, Kompella UB. Local delivery of biodegradable pirfenidone nanoparticles ameliorates bleomycin-induced pulmonary fibrosis in mice. Nanotechnology. 2012;23(50):505101.
Nathan SD, Lancaster LH, Albera C, Glassberg MK, Swigris JJ, Gilberg F, et al. Dose modification and dose intensity during treatment with pirfenidone: analysis of pooled data from three multinational phase III trials. BMJ open respiratory research. 2018;5(1).
Tian X, Yao W, Guo Z, Gu L, Zhu Y. Low dose pirfenidone suppresses transforming growth factor beta-1 and tissue inhibitor of metalloproteinase-1, and protects rats from lung fibrosis induced by bleomycina. Chinese medical sciences journal= Chung-kuo i hsueh k'o hsueh tsa chih. 2006;21(3):145-51.
Seto Y, Suzuki G, Leung SSY, Chan H-K, Onoue S. Development of an Improved Inhalable Powder Formulation of Pirfenidone by Spray- Drying: In Vitro Characterization and Pharmacokinetic Profiling. Pharmaceutical research. 2016;33(6):1447-55.
Khoo JK, Montgomery AB, Otto KL, Surber M, Faggian J, Lickliter JD, et al. A randomized, double-blinded, placebo-controlled, dose-escalation phase 1 study of aerosolized Pirfenidone delivered via the PARI investigational eFlow nebulizer in volunteers and patients with idiopathic pulmonary fibrosis. Journal of Aerosol Medicine and Pulmonary Drug Delivery. 2020;33(1):15-20.
Cheng Y-S, Zhou Y, Chen BT. Particle deposition in a cast of human oral airways. Aerosol Science & Technology. 1999;31(4):286-300.
Tang P, Chan H-K, Raper JA. Prediction of aerodynamic diameter of particles with rough surfaces. Powder technology. 2004;147(1- 3):64-78.
Wiggins NA. The development of a mathematical approximation technique to determine the mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of drug particles in an inhalation aerosol sprat. Drug development and industrial pharmacy. 1991;17(14):1971-86.
Vanbever R, Mintzes JD, Wang J, Nice J, Chen D, Batycky R, et al. Formulation and physical characterization of large porous particles for inhalation. Pharmaceutical research. 1999;16(11):1735-42.
Gupta R, Byron PR, Vanbever R, Mintzes J. Physical characterization of large porous particles for inhalation. Pharmaceutical research. 2000;17(11):1437.
Reponen T, Willeke K, Ulevicius V, Reponen A, Grinshpun SA. Effect of relative humidity on the aerodynamic diameter and respiratory deposition of fungal spores. Atmospheric Environment. 1996;30(23):3967-74.
Young PM, Sung A, Traini D, Kwok P, Chiou H, Chan H-K. Influence of humidity on the electrostatic charge and aerosol performance of dry powder inhaler carrier based systems. Pharmaceutical research. 2007;24(5):963-70.
Price R, Young P, Edge S, Staniforth J. The influence of relative humidity on particulate interactions in carrier-based dry powder inhaler formulations. International journal of pharmaceutics. 2002;246(1-2):47-59.
Haddrell AE, Davies JF, Reid JP. Dynamics of particle size on inhalation of environmental aerosol and impact on deposition fraction. Environmental Science & Technology. 2015;49(24):14512- 21.
Musante CJ, Schroeter JD, Rosati JA, Crowder TM, Hickey AJ, Martonen TB. Factors affecting the deposition of inhaled porous drug particles. Journal of pharmaceutical sciences. 2002;91(7):1590-600.
Hickey AJ. Controlled delivery of inhaled therapeutic agents. Journal of Controlled Release. 2014;190:182-8.
Cheng YS. Mechanisms of pharmaceutical aerosol deposition in the respiratory tract. AAPS PharmSciTech. 2014;15(3):630-40.
Stahlhofen W, Gebhart J, Heyder J. Experimental determination of the regional deposition of aerosol particles in the human respiratory tract. American Industrial Hygiene Association Journal. 1980;41(6):385-98a.
Darquenne C. Aerosol deposition in health and disease. Journal of aerosol medicine and pulmonary drug delivery. 2012;25(3):140-7.
Darquenne C. Deposition mechanisms. Journal of aerosol medicine and pulmonary drug delivery. 2020;33(4):181-5.
Tcharkhtchi A, Abbasnezhad N, Seydani MZ, Zirak N, Farzaneh S, S hirinbayan M . A n o verview o f f iltration e fficiency t hrough the masks: Mechanisms of the aerosols penetration. Bioactive materials. 2020;6(1):106-22.
Deng Q, Deng L, Miao Y, Guo X, Li Y. Particle deposition in the human lung: Health implications of particulate matter from different sources. Environmental research. 2019;169:237-45.
Chen X, Feng Y, Zhong W, Sun B, Tao F. Numerical investigation of particle deposition in a triple bifurcation airway due to gravitational sedimentation and inertial impaction. Powder Technology. 2018;323:284-93.
Sonnenberg AH, Herrmann J, Grinstaff MW, Suki B. A Markov chain model of particle deposition in the lung. Scientific reports. 2020;10(1):1-12.
Wang L, Zheng K, Ding Z, Yan X, Zhang H, Cao Y, et al. Drag coefficient and settling velocity of fine particles with varying surface wettability. Powder Technology. 2020.
Conway J. Lung imaging—two dimensional gamma scintigraphy, S PEC T, C T a nd PE T. Adv a nc e d d r u g del i ver y r ev iew s . 2012;64(4):357-68.
Crowder TM, Rosati JA, Schroeter JD, Hickey AJ, Martonen TB. Fundamental effects of particle morphology on lung delivery: predictions of Stokes' law and the particular relevance to dry powder inhaler formulation and development. Pharmaceutical research. 2002;19(3):239-45.
Petersson J, Sánchez-Crespo A, Larsson SA, Mure M. Physiological imag ing of t he lu ng: sing le-phot on-emission comput ed tomography (SPECT). Journal of applied physiology. 2007;102(1): 468-76.
Lynch DA, Godwin JD, Safrin S, Starko KM, Hormel P, Brown KK, et al. High-resolution computed tomography in idiopathic pulmonary fibrosis: diagnosis and prognosis. American journal of respiratory and critical care medicine. 2005;172(4):488-93.
Lardinois D, Weder W, Hany TF, Kamel EM, Korom S, Seifert B, et al. Staging of non–small-cell lung cancer with integrated positron-emission tomography and computed tomography. New England Journal of Medicine. 2003;348(25):2500-7.
Labiris N, Dolov ich M. Pulmonar y dr ug deliver y. Par t I: physiological factors affecting therapeutic effectiveness of aerosolized medications. British journal of clinical pharmacology. 2003;56(6):588-99.
Labiris NR, Dolovich MB. Pulmonary drug delivery. Part II: the role of inhalant delivery devices and drug formulations in therapeutic effectiveness of aerosolized medications. British journal of clinical pharmacology. 2003;56(6):600-12.
Kim CS, Fisher DM, Lutz DJ, Gerrity TR. Particle deposition in bifurcating airway models with varying airway geometry. Journal of Aerosol Science. 1994;25(3):567-81.
Cheng Y, Yeh H, Guilmette R, Simpson S, Cheng K, Swift D. Nasal deposition of ultrafine particles in human volunteers and its relationship to airway geometry. Aerosol Science and Technology. 1996;25(3):274-91.
Henning A, Schneider M, Nafee N, Muijs L, Rytting E, Wang X, et al. Influence of particle size and material properties on mucociliary clearance from the airways. Journal of aerosol medicine and pulmonary drug delivery. 2010;23(4):233-41.
Li Z, Kleinstreuer C, Zhang Z. Particle deposition in the human tracheobronchial airways due to transient inspiratory f low patterns. Journal of aerosol science. 2007;38(6):625-44.
Darquenne C, Paiva M, Prisk GK. Effect of gravity on aerosol dispersion and deposition in the human lung after periods of breath holding. Journal of Applied Physiology. 2000;89(5):1787-92.
Frijlink H, De Boer A. Dry powder inhalers for pulmonary drug delivery. Expert opinion on drug delivery. 2004;1(1):67-86.
Edwards DA, Hanes J, Caponetti G, Hrkach J, Ben-Jebria A, Eskew ML, et al. Large porous particles for pulmonary drug delivery. Science. 1997;276(5320):1868-72.
Yang MY, Chan JGY, Chan H-K. Pulmonary drug delivery by powder aerosols. Journal of Controlled Release. 2014;193:228-40.
Timsina M, Martin G, Marriott C, Ganderton D, Yianneskis M. Drug delivery to the respiratory tract using dry powder inhalers. International journal of pharmaceutics. 1994;101(1-2):1-13.
Byron PR. Prediction of drug residence times in regions of the human respiratory tract following aerosol inhalation. Journal of pharmaceutical sciences. 1986;75(5):433-8.
Lansley AB. Mucociliary clearance and drug delivery via the respiratory tract. Advanced drug delivery reviews. 1993;11(3):299- 327.
Schipper NG, Verhoef JC, Merkus FW. The nasal mucociliary clearance: relevance to nasal drug delivery. Pharmaceutical research. 1991;8(7):807-14.
Chatburn R L . High-f requenc y assisted air way clearance. Respiratory care. 2007;52(9):1224-37.
Dhand R, Mercier E. Effective inhaled drug administration to mechanically ventilated patients. Expert opinion on drug delivery. 2007;4(1):47-61.
Secret E, Kelly SJ, Crannell KE, Andrew JS. Enzyme-responsive hydrogel microparticles for pulmonary drug delivery. ACS applied materials & interfaces. 2014;6(13):10313-21.
El‐Sherbiny IM, McGill S, Smyth HD. Swellable microparticles as carriers for sustained pulmonary drug delivery. Journal of pharmaceutical sciences. 2010;99(5):2343-56.
El-Sherbiny IM, Smyth HD. Biodegradable nano-micro carrier systems for sustained pulmonary drug delivery:(I) self-assembled nanoparticles encapsulated in respirable/swellable semi-IPN microspheres. International journal of pharmaceutics. 2010;395(1- 2):132-41.
Vyas SP, Khatri K. Liposome-based drug delivery to alveolar macrophages. Expert opinion on drug delivery. 2007;4(2):95-9.
Chono S, Tanino T, Seki T, Morimoto K. Efficient drug delivery to alveolar macrophages and lung epithelial lining fluid following pulmonary administration of liposomal ciprofloxacin in rats with pneumonia and estimation of its antibacterial effects. Drug development and industrial pharmacy. 2008;34(10):1090-6.
Woods A, Patel A, Spina D, Riffo-Vasquez Y, Babin-Morgan A, de Rosales R, et al. In vivo biocompatibility, clearance, and biodistribution of albumin vehicles for pulmonary drug delivery. Journal of Controlled Release. 2015;210:1-9.
Minneman Kp, Hegstrand Lr, Molinoff Pb. The pharmacological specificity of beta-1 and beta-2 adrenergic receptors in rat heart and lung in vitro. Molecular Pharmacology. 1979;16(1):21-33.
Barnes PJ. Muscarinic receptor subtypes in airways. Life sciences. 1993;52(5-6):521-7.
Barnes P. Histamine receptors in the lung. Agents and actions Supplements. 1991;33:103-22.
Barnes PJ. Distribution of receptor targets in the lung. Proceedings of the American Thoracic Society. 2004;1(4):345-51.
Bennett WD, Zeman KL, Kim C. Variability of fine particle deposition in healthy adults: effect of age and gender. American journal of respiratory and critical care medicine. 1996;153(5):1641-7.
Kim CS, Kang TC. Comparative measurement of lung deposition of inhaled fine particles in normal subjects and patients with obstructive airway disease. American journal of respiratory and critical care medicine. 1997;155(3):899-905.
Salma I, Balásházy I, Winkler-Heil R, Hofmann W, Záray G. Effect of particle mass size distribution on the deposition of aerosols in the human respiratory system. Journal of Aerosol Science. 2002;33(1):119-32.
Goodman DE, Israel E, Rosenberg M, Johnston R, Weiss ST, Drazen JM. The influence of age, diagnosis, and gender on proper use of metered-dose inhalers. American journal of respiratory and critical care medicine. 1994;150(5):1256-61.
Pichelin M, Caillibotte G, Katz I, Martonen T. Categorization of lung morphology based on FRC and height: computer simulations of aerosol deposition. Aerosol Science and Technology. 2012;46(1):70- 81.
Saiful Hassan M, Lau R. Effect of particle formulation on dry powder inhalation efficiency. Current pharmaceutical design. 2010;16(21):2377-87.
Mohammed H, Roberts DL, Copley M, Hammond M, Nichols SC, Mitchell JP. Effect of sampling volume on dry powder inhaler (DPI)- emitted aerosol aerodynamic particle size distributions (APSDs) measured by the Next-Generation Pharmaceutical Impactor (NGI) and the Andersen eight-stage cascade impactor (ACI). Aaps Pharmscitech. 2012;13(3):875-82.
DeCarlo PF, Slowik JG, Worsnop DR, Davidovits P, Jimenez JL. Particle morphology and density characterization by combined mobility and aerodynamic diameter measurements. Part 1: Theory. Aerosol Science and Technology. 2004;38(12):1185-205.
Chew NY, Tang P, Chan H-K, Raper JA. How much particle surface corrugation is sufficient to improve aerosol performance of powders? Pharmaceutical research. 2005;22(1):148-52.
Begat P, Morton DA, Staniforth JN, Price R. The cohesive-adhesive balances in dry powder inhaler formulations II: influence on fine particle delivery characteristics. Pharmaceutical research. 2004;21(10):1826-33.
Scherließ R, Etschmann C. DPI formulations for high dose applications–Challenges and opportunities. International journal of pharmaceutics. 2018;548(1):49-53.
Kumar TP, Vani MI, Yamini D, Raju PN, Reddy GN. Recent advances in nasal formulations and devices used in pulmonary drug delivery. World J Pharm Pharm Sci. 2013;2:3759-78.
Islam N, Gladki E. Dry powder inhalers (DPIs)—a review of device reliability and innovation. International journal of pharmaceutics. 2008;360(1-2):1-11.
Gradon L, Sosnowski TR. Formation of particles for dry powder inhalers. Advanced Powder Technology. 2014;25(1):43-55.
McCallion O, Taylor K, Bridges P, Thomas M, Taylor A . Jet nebulisers for pulmonary drug delivery. International Journal of Pharmaceutics. 1996;130(1):1-11.
Yeo LY, Friend JR, McIntosh MP, Meeusen EN, Morton DA. Ultrasonic nebulization platforms for pulmonary drug delivery. Expert opinion on drug delivery. 2010;7(6):663-79.
Pilcer G, Amighi K. Formulation strategy and use of excipients in pulmonary drug delivery. International journal of pharmaceutics. 2010;392(1-2):1-19.
Tashkin DP. A review of nebulized drug delivery in COPD. International journal of chronic obstructive pulmonary disease. 2016;11:2585.
Smyth HD. Propellant-driven metered-dose inhalers for pulmonary drug delivery. Expert opinion on drug delivery. 2005;2(1):53-74.
Newman SP. Principles of metered-dose inhaler design. Respiratory care. 2005;50(9):1177-90.
Leach CL. The CFC to HFA transition and its impact on pulmonary drug development. Respiratory care. 2005;50(9):1201-8.
Shoyele SA, Cawthorne S. Particle engineering techniques for inhaled biopharmaceuticals. Advanced drug delivery reviews. 2006;58(9-10):1009-29.
Müller RH, Shegokar R, Gohla S, Keck CM. Nanocrystals: production, cellular drug delivery, current and future products. Intracellular Delivery: Springer; 2011. p. 411-32.
Steckel H, Brandes HG. A novel spray-drying technique to produce low density particles for pulmonary delivery. International journal of pharmaceutics. 2004;278(1):187-95.
Beck-Broichsitter M, Schweiger C, Schmehl T, Gessler T, Seeger W, Kissel T. Characterization of novel spray-dried polymeric particles for controlled pulmonary drug delivery. Journal of controlled release. 2012;158(2):329-35.
Klingler C, Müller BW, Steckel H. Insulin-micro-and nanoparticles for pulmonary delivery. International journal of pharmaceutics. 2009;377(1-2):173-9.
Shoyele SA, Slowey A. Prospects of formulating proteins/peptides as aerosols for pulmonary drug delivery. International journal of pharmaceutics. 2006;314(1):1-8.
Liang W, Chow MY, Lau PN, Zhou QT, Kwok PC, Leung GP, et al. Inhalable dry powder formulations of siRNA and pH-responsive peptides with antiviral activity against H1N1 influenza virus. Molecular pharmaceutics. 2015;12(3):910-21.
V i s h a l i D , M o n i s h a J , S i v a k a m a s u n d a r i S , M o s e s J , Anandharamak rishnan C . Spray freeze dr y ing: Emerging applications in drug delivery. Journal of Controlled Release. 2019;300:93-101.
Sahakijpijarn S, Moon C, Ma X, Su Y, Koleng JJ, Dolocan A, et al. Using thin film freezing to minimize excipients in inhalable tacrolimus dry powder formulations. International Journal of Pharmaceutics. 2020;586:119490.
Carvalho SR, Watts AB, Peters JI, Williams RO. Dry powder inhalation for pulmonary delivery: recent advances and continuing challenges. Pulmonary Drug Delivery Advances and Challenges (Advances in Pharmaceutical Technology), John Wiley & Sons, Chichester, UK. 2015:35-62.
Reisner C, Fabbri LM, Kerwin EM, Fogarty C, Spangenthal S, Rabe KF, et al. A randomized, seven-day study to assess the efficacy and safety of a glycopyrrolate/formoterol fumarate fixed-dose combination metered dose inhaler using novel Co-Suspension™ Delivery Technology in patients with moderate-to-very severe chronic obstructive pulmonary disease. Respiratory research. 2017;18(1):8.
Vogelmeier CF, Bateman ED, Pallante J, Alagappan VK, D'Andrea P, Chen H, et al. Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol–fluticasone in patients with chronic obstructive pulmonary disease (ILLUMINATE): a randomised, double-blind, parallel group study. The Lancet Respiratory Medicine. 2013;1(1):51-60.
Gessner C, Kornmann O, Maspero J, van Zyl-Smit R, Krüll M, Salina A, et al. Fixed-dose combination of indacaterol/glycopyrronium/ mometasone furoate once-daily versus salmeterol/fluticasone twice-daily plus tiotropium once-daily in patients with uncontrolled asthma: A randomised, Phase IIIb, non-inferiority study (ARGON). Respiratory Medicine. 2020:106021.
Tashkin DP, Martinez FJ, Rodriguez-Roisin R, Fogarty C, Gotfried M, Denenberg M, et al. A multicenter, randomized, double-blind dose-ranging study of glycopyrrolate/formoterol fumarate fixed-dose combination metered dose inhaler compared to the monocomponents and open-label tiotropium dry powder inhaler in patients with moderate-to-severe COPD. Respiratory medicine. 2016;120:16-24.
Dave V, Tak K, Sohgaura A, Gupta A, Sadhu V, Reddy KR. Lipid-polymer hybrid nanoparticles: Synthesis strategies and biomedical applications. Journal of microbiological methods. 2019;160:130-42.
Rytting E, Nguyen J, Wang X, Kissel T. Biodegradable polymeric nanocarriers for pulmonary drug delivery. Expert opinion on drug delivery. 2008;5(6):629-39.
Kammona O, Kiparissides C. Recent advances in nanocarrier-based mucosal delivery of biomolecules. Journal of controlled release. 2012;161(3):781-94.
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