{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:50:59Z","timestamp":1791546659768,"version":"4.3.4"},"reference-count":100,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T00:00:00Z","timestamp":1669766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"School of Pharmacy\u2019s Marsden Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Dry powder inhalation therapy has been effective in treating localized lung diseases such asthma, chronic obstructive pulmonary diseases (COPD), cystic fibrosis and lung infections. In vitro characterization of dry powder formulations includes the determination of physicochemical nature and aerosol performance of powder particles. The relationship between particle properties (size, shape, surface morphology, porosity, solid state nature, and surface hydrophobicity) and aerosol performance of an inhalable dry powder formulation has been well established. However, unlike oral formulations, there is no standard dissolution method for evaluating the dissolution behavior of the inhalable dry powder particles in the lungs. This review focuses on various dissolution systems and absorption models, which have been developed to evaluate dry powder formulations. It covers a summary of airway epithelium, hurdles to developing an in vitro dissolution method for the inhaled dry powder particles, fine particle dose collection methods, various in vitro dissolution testing methods developed for dry powder particles, and models commonly used to study absorption of inhaled drug.<\/jats:p>","DOI":"10.3390\/pharmaceutics14122667","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T05:45:22Z","timestamp":1669787122000},"page":"2667","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Dissolution and Absorption of Inhaled Drug Particles in the Lungs"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8462-4181","authenticated-orcid":false,"given":"Basanth Babu","family":"Eedara","sequence":"first","affiliation":[{"name":"School of Pharmacy, University of Otago, Dunedin 9054, New Zealand"},{"name":"Center for Translational Science, Florida International University, Port St. Lucie, FL 34987, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh","family":"Bastola","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Otago, Dunedin 9054, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyamal C.","family":"Das","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Otago, Dunedin 9054, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8290963","DOI":"10.1155\/2016\/8290963","article-title":"Dry Powder Inhalers: A Focus on Advancements in Novel Drug Delivery Systems","volume":"2016","author":"Mehta","year":"2016","journal-title":"J. Drug Deliv."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Eedara, B.B., Alabsi, W., Encinas-Basurto, D., Polt, R., Ledford, J.G., and Mansour, H.M. (2021). Inhalation Delivery for the Treatment and Prevention of COVID-19 Infection. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13071077"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1208\/s12249-021-02043-5","article-title":"Spray-Dried Inhalable Powder Formulations of Therapeutic Proteins and Peptides","volume":"22","author":"Eedara","year":"2021","journal-title":"AAPS PharmSciTech"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Alabsi, W., Eedara, B.B., Encinas-Basurto, D., Polt, R., and Mansour, H.M. (2022). Nose-to-Brain Delivery of Therapeutic Peptides as Nasal Aerosols. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14091870"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1517\/17425247.1.1.67","article-title":"Dry powder inhalers for pulmonary drug delivery","volume":"1","author":"Frijlink","year":"2004","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1517\/17425247.2015.977783","article-title":"Dry powder inhalers in COPD, lung inflammation and pulmonary infections","volume":"12","author":"Muralidharan","year":"2015","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1183\/09059180.05.00009605","article-title":"Inhaler treatment options in COPD","volume":"14","author":"Newman","year":"2005","journal-title":"Eur. Respir. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S1094-5539(02)00147-5","article-title":"The inhalers of the future? A review of dry powder devices on the market today","volume":"16","author":"Smith","year":"2003","journal-title":"Pulm Pharmacol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Svedsater, H., Dale, P., Garrill, K., Walker, R., and Woepse, M.W. (2013). Qualitative assessment of attributes and ease of use of the ELLIPTA\u2122 dry powder inhaler for delivery of maintenance therapy for asthma and COPD. BMC Pulm Med., 13.","DOI":"10.1186\/1471-2466-13-72"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Eedara, B.B., Alabsi, W., Encinas-Basurto, D., Polt, R., Hayes, D., Black, S.M., and Mansour, H.M. (2021). Pulmonary Drug Delivery. Organelle and Molecular Targeting, CRC Press.","DOI":"10.1201\/9781003092773-8"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2","DOI":"10.5339\/gcsp.2015.2","article-title":"Inhaled nano- and microparticles for drug delivery","volume":"2015","author":"Yacoub","year":"2015","journal-title":"Glob. Cardiol. Sci. Pract."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1517\/14712598.4.1.23","article-title":"Dry powder inhalers for optimal drug delivery","volume":"4","author":"Newman","year":"2004","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Olsson, B., Bondesson, E., Borgstr\u00f6m, L., Edsb\u00e4cker, S., Eirefelt, S., Ekelund, K., Gustavsson, L., and Hegelund-Myrb\u00e4ck, T. (2011). Pulmonary drug metabolism, clearance, and absorption. Controlled Pulmonary Drug Delivery, Springer.","DOI":"10.1007\/978-1-4419-9745-6_2"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S-71","DOI":"10.1089\/jamp.2010.0836","article-title":"The Particle has Landed\u2014Characterizing the Fate of Inhaled Pharmaceuticals","volume":"23","author":"Patton","year":"2010","journal-title":"J. Aerosol. Med. Pulm. Drug Deliv."},{"key":"ref_15","unstructured":"Eedara, B.B. (2019). Slow Dissolving Inhalable Dry Powders for Treatment of Pulmonary Tuberculosis, University of Otago."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Smyth, H.D.C., and Hickey, A.J. (2011). Controlled Pulmonary Drug Delivery, Springer. [1st ed.].","DOI":"10.1007\/978-1-4419-9745-6"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Smyth, H.D.C., and Hickey, A.J. (2011). Overcoming Lung Clearance Mechanisms for Controlled Release Drug Delivery. Controlled Pulmonary Drug Delivery, Springer.","DOI":"10.1007\/978-1-4419-9745-6"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"104961","DOI":"10.1016\/j.ejps.2019.104961","article-title":"Crystalline adduct of moxifloxacin with trans-cinnamic acid to reduce the aqueous solubility and dissolution rate for improved residence time in the lungs","volume":"136","author":"Eedara","year":"2019","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_19","unstructured":"FDAU (1997). Guidance for Industry: Dissolution Testing of Immediate-Release Solid Oral Dosage Forms, Center for Drug Evaluation and Research (CDER)."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1007\/s11095-010-0070-5","article-title":"In Vitro Aqueous Fluid-Capacity-Limited Dissolution Testing of Respirable Aerosol Drug Particles Generated from Inhaler Products","volume":"27","author":"Arora","year":"2010","journal-title":"Pharm. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0378-5173(03)00091-7","article-title":"A novel method for assessing dissolution of aerosol inhaler products","volume":"255","author":"Davies","year":"2003","journal-title":"Int. J. Pharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1111\/1523-1747.ep12533356","article-title":"Percutaneous Absorption. On the Relevance of in Vitro Data","volume":"64","author":"Franz","year":"1975","journal-title":"J. Investig. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1089\/adt.2017.779","article-title":"DissolvIt: An In Vitro Method for Simulating the Dissolution and Absorption of Inhaled Dry Powder Drugs in the Lungs","volume":"15","author":"Gerde","year":"2017","journal-title":"ASSAY Drug Dev. Technol."},{"key":"ref_24","first-page":"1068","article-title":"The Inhalation Ad Hoc Advisory Panel for the USP Performance Tests of Inhalation Dosage Forms","volume":"34","author":"Gray","year":"2008","journal-title":"Pharmacop. Forum"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1007\/s11095-012-0744-2","article-title":"Dissolution Techniques for In Vitro Testing of Dry Powders for Inhalation","volume":"29","author":"May","year":"2012","journal-title":"Pharm. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.1021\/acs.molpharmaceut.5b00221","article-title":"Evaluation of the Transwell System for Characterization of Dissolution Behavior of Inhalation Drugs: Effects of Membrane and Surfactant","volume":"12","author":"Rohrschneider","year":"2015","journal-title":"Mol. Pharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.ejpb.2008.04.009","article-title":"Preparation and characterisation of controlled release co-spray dried drug\u2013polymer microparticles for inhalation 2: Evaluation of in vitro release profiling methodologies for controlled release respiratory aerosols","volume":"70","author":"Salama","year":"2008","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.ijpharm.2009.07.034","article-title":"Development of a standardized dissolution test method for inhaled pharmaceutical formulations","volume":"382","author":"Son","year":"2009","journal-title":"Int. J. Pharm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1517\/17425240903117244","article-title":"Assessment methods of inhaled aerosols: Technical aspects and applications","volume":"6","author":"Andrieu","year":"2009","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1080\/17425247.2021.1882991","article-title":"Simulation of respiratory tract lining fluid for in vitro dissolution study","volume":"18","author":"Bastola","year":"2021","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s41120-015-0002-x","article-title":"Scope and relevance of a pulmonary biopharmaceutical classification system AAPS\/FDA\/USP Workshop 16\u201317 March 2015 in Baltimore, MD","volume":"2","author":"Hastedt","year":"2016","journal-title":"AAPS Open"},{"key":"ref_32","first-page":"7","article-title":"Functional design of the human lung for gas exchange","volume":"Volume 1","author":"Grippi","year":"2015","journal-title":"Fishman\u2019s Pulmonary Diseases and Disorders"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.pharmthera.2014.05.003","article-title":"Across the pulmonary epithelial barrier: Integration of physicochemical properties and human cell models to study pulmonary drug formulations","volume":"144","author":"Haghi","year":"2014","journal-title":"Pharmacol. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.addr.2010.11.002","article-title":"Formation, characterization, and fate of inhaled drug nanoparticles","volume":"63","author":"Zhang","year":"2011","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ijpharm.2018.03.005","article-title":"The influence of surface active l-leucine and 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) in the improvement of aerosolization of pyrazinamide and moxifloxacin co-spray dried powders","volume":"542","author":"Eedara","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.ejps.2018.04.003","article-title":"Development and characterization of high payload combination dry powders of anti-tubercular drugs for treating pulmonary tuberculosis","volume":"118","author":"Eedara","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.ijpharm.2016.04.038","article-title":"Phospholipid-based pyrazinamide spray-dried inhalable powders for treating tuberculosis","volume":"506","author":"Eedara","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"118689","DOI":"10.1016\/j.ijpharm.2019.118689","article-title":"Bedaquiline containing triple combination powder for inhalation to treat drug-resistant tuberculosis","volume":"570","author":"Rangnekar","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1080\/10717544.2017.1333172","article-title":"Toxicity of orally inhaled drug formulations at the alveolar barrier: Parameters for initial biological screening","volume":"24","year":"2017","journal-title":"Drug Deliv."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0013-9351(87)80241-4","article-title":"A mathematical model of the penetration of polycyclic aromatic hydrocarbons through the bronchial lining layer","volume":"44","author":"Gerde","year":"1987","journal-title":"Environ. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/nrd2153","article-title":"Inhaling medicines: Delivering drugs to the body through the lungs","volume":"6","author":"Patton","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.chemphyslip.2014.09.002","article-title":"Composition, structure and mechanical properties define performance of pulmonary surfactant membranes and films","volume":"185","author":"Parra","year":"2015","journal-title":"Chem. Phys. Lipids"},{"key":"ref_43","unstructured":"Broaddus, V.C., Mason, R.J., Ernst, J.D., King, T.E., Lazarus, S.C., Murray, J.F., Nadel, J.A., Slutsky, A.S., and Gotway, M.B. (2016). Alveolar Epithelium and Pulmonary Surfactant. Murray and Nadel\u2019s Textbook of Respiratory Medicine, Elsevier."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2010.12.040","article-title":"Influence of particle size on regional lung deposition\u2014What evidence is there?","volume":"406","author":"Carvalho","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.addr.2014.05.001","article-title":"Lipid-based carriers for pulmonary products: Preclinical development and case studies in humans","volume":"75","author":"Cipolla","year":"2014","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_46","unstructured":"(2022, September 21). Driving Results in Inhaler Testing [Brochure]. Available online: https:\/\/www.copleyscientific.com\/wp-content\/uploads\/2020\/02\/Copley-Inhaler-Testing-Brochure-LowRes-0720.pdf."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3211","DOI":"10.1007\/s11095-014-1413-4","article-title":"Dissolution Testing of Powders for Inhalation: Influence of Particle Deposition and Modeling of Dissolution Profiles","volume":"31","author":"May","year":"2014","journal-title":"Pharm. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"40","DOI":"10.14227\/DT220315P40","article-title":"Miniature in vitro dissolution testing of powders for inhalation","volume":"22","author":"May","year":"2015","journal-title":"Dissolution Technol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ijpharm.2018.04.048","article-title":"Dissolution of fine particle fraction from truncated Anderson cascade impactor with an enhancer cell","volume":"545","author":"Tay","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6","DOI":"10.14227\/DT170210P6","article-title":"Optimization of an in vitro dissolution test method for inhalation formulations","volume":"17","author":"Son","year":"2010","journal-title":"Dissolution Technol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1111\/j.2042-7158.2012.01531.x","article-title":"Preparation of sustained release rifampicin microparticles for inhalation","volume":"64","author":"Son","year":"2012","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ijpharm.2012.03.002","article-title":"Solid dispersions of itraconazole for inhalation with enhanced dissolution, solubility and dispersion properties","volume":"428","author":"Duret","year":"2012","journal-title":"Int. J. Pharm."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1002\/jps.23525","article-title":"New Co-Spray-Dried Tobramycin Nanoparticles-Clarithromycin Inhaled Powder Systems for Lung Infection Therapy in Cystic Fibrosis Patients","volume":"102","author":"Pilcer","year":"2013","journal-title":"J. Pharm. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.ejpb.2012.08.007","article-title":"A novel dry powder inhalable formulation incorporating three first-line anti-tubercular antibiotics","volume":"83","author":"Chan","year":"2013","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.ejpb.2008.09.006","article-title":"The permeability of large molecular weight solutes following particle delivery to air-interfaced cells that model the respiratory mucosa","volume":"71","author":"Grainger","year":"2009","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1021\/mp200415g","article-title":"Critical Characteristics for Corticosteroid Solution Metered Dose Inhaler Bioequivalence","volume":"9","author":"Grainger","year":"2012","journal-title":"Mol. Pharm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1021\/mp200620m","article-title":"Deposition, Diffusion and Transport Mechanism of Dry Powder Microparticulate Salbutamol, at the Respiratory Epithelia","volume":"9","author":"Haghi","year":"2012","journal-title":"Mol. Pharm."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.ijpharm.2019.01.035","article-title":"In vitro dissolution testing of respirable size anti-tubercular drug particles using a small volume dissolution apparatus","volume":"559","author":"Eedara","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_59","unstructured":"B\u00f6rjel, M., Sadler, R., and Gerde, P. (2014). The dissolvIt: An in vitro evaluation of the dissolution and absorption of three inhaled dry powder drugs in the lung. Respiratory Drug Delivery to the Lungs Conference, Poster Stockholm, Karolinska Institutet."},{"key":"ref_60","unstructured":"(2018). British Pharmacopoeia, TSO."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.ejpb.2011.02.004","article-title":"A new respirable form of rifampicin","volume":"78","author":"Son","year":"2011","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"18522","DOI":"10.1038\/s41598-019-55164-0","article-title":"A STELLA simulation model for in vitro dissolution testing of respirable size particles","volume":"9","author":"Eedara","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.xphs.2021.09.042","article-title":"In-Vitro In-Vivo Correlation (IVIVC) of Inhaled Products Using Twin Stage Impinger","volume":"111","author":"Buzgeia","year":"2022","journal-title":"J. Pharm. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1080\/08958370490258381","article-title":"A Novel Method to Aerosolize Powder for Short Inhalation Exposures at High Concentrations: Isolated Rat Lungs Exposed to Respirable Diesel Soot","volume":"16","author":"Gerde","year":"2004","journal-title":"Inhal. Toxicol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ejpb.2006.07.006","article-title":"Solid lipid microparticles as a sustained release system for pulmonary drug delivery","volume":"65","author":"Jaspart","year":"2007","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1208\/s12249-015-0283-3","article-title":"Development of Novel Chitosan Microcapsules for Pulmonary Delivery of Dapsone: Characterization, Aerosol Performance, and In Vivo Toxicity Evaluation","volume":"16","author":"Ortiz","year":"2015","journal-title":"AAPS PharmSciTech"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ijpharm.2003.11.001","article-title":"Theophylline particle design using chitosan by the spray drying","volume":"270","author":"Asada","year":"2004","journal-title":"Int. J. Pharm."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1080\/0265204021000058456","article-title":"The characteristics of betamethasone-loaded chitosan microparticles by spray-drying method","volume":"20","author":"Huang","year":"2003","journal-title":"J. Microencapsul."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.ejpb.2007.04.017","article-title":"Chitosan-based spray-dried respirable powders for sustained delivery of terbutaline sulfate","volume":"68","author":"Learoyd","year":"2008","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ejpb.2011.09.015","article-title":"Comparative pharmacoscintigraphic and pharmacokinetic evaluation of two new formulations of inhaled insulin in type 1 diabetic patients","volume":"80","author":"Depreter","year":"2012","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.powtec.2014.04.077","article-title":"Preparation and characterization of controlled release poly-\u03b5-caprolactone microparticles of isoniazid for drug delivery through pulmonary route","volume":"264","author":"Parikh","year":"2014","journal-title":"Powder Technol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1021\/mp500808t","article-title":"Development of an Inhaled Controlled Release Voriconazole Dry Powder Formulation for the Treatment of Respiratory Fungal Infection","volume":"12","author":"Arora","year":"2015","journal-title":"Mol. Pharm."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1089\/jamp.2014.1187","article-title":"Development and Evaluation of Chitosan Microparticles Based Dry Powder Inhalation Formulations of Rifampicin and Rifabutin","volume":"29","author":"Pai","year":"2016","journal-title":"J. Aerosol Med. Pulm. Drug Deliv."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.ijpharm.2016.07.062","article-title":"Solid Lipid Nanoparticle assemblies (SLNas) for an anti-TB inhalation treatment\u2014A Design of Experiments approach to investigate the influence of pre-freezing conditions on the powder respirability","volume":"511","author":"Maretti","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"136","DOI":"10.4103\/0250-474X.180261","article-title":"Development of an Inhaled Sustained Release Dry Powder Formulation of Salbutamol Sulphate, an Antiasthmatic Drug","volume":"78","author":"Kumaresan","year":"2016","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1080\/10837450600769637","article-title":"Manufacture, Characterization, and Pharmacodynamic Evaluation of Engineered Ipratropium Bromide Particles","volume":"11","author":"Taylor","year":"2006","journal-title":"Pharm. Dev. Technol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.jconrel.2005.01.003","article-title":"Novel sustained release microspheres for pulmonary drug delivery","volume":"104","author":"Cook","year":"2005","journal-title":"J. Control. Release"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3109\/03639040903099769","article-title":"Controlled release antibiotics for dry powder lung delivery","volume":"36","author":"Adi","year":"2010","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ejpb.2012.01.018","article-title":"Zinc\u2013alginate microparticles for controlled pulmonary delivery of proteins prepared by spray-drying","volume":"81","author":"Siepmann","year":"2012","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"225","DOI":"10.3109\/02652048.2011.646326","article-title":"Preparation and in vitro evaluation of salbutamol-loaded lipid microparticles for sustained release pulmonary therapy","volume":"29","author":"Scalia","year":"2012","journal-title":"J. Microencapsul."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.ijpharm.2014.01.033","article-title":"Differences in physical chemistry and dissolution rate of solid particle aerosols from solution pressurised inhalers","volume":"465","author":"Buttini","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.jddst.2015.07.010","article-title":"High shear mixing of lactose and salmeterol xinafoate dry powder blends: Biopharmaceutic and aerodynamic performances","volume":"30","author":"Balducci","year":"2015","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_83","first-page":"1276","article-title":"Standardized flow-cell method as an alternative to existing pharmacopoeial dissolution testing","volume":"51","author":"Langenbucher","year":"1989","journal-title":"Pharm. Ind."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"46","DOI":"10.14227\/DT180411P46","article-title":"Flow-through cell apparatus (USP apparatus 4): Operation and features","volume":"18","author":"Fotaki","year":"2011","journal-title":"Dissolut. Technol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1097\/00004032-197305000-00004","article-title":"Measurement of in Vitro Dissolution of Aerosol Particles for Comparison to in Vivo Dissolution in the Lower Respiratory Tract after Inhalation","volume":"24","author":"Kanapilly","year":"1973","journal-title":"Health Phys."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1208\/s12249-012-9822-3","article-title":"Challenges with developing in vitro dissolution tests for orally inhaled products (OIPs)","volume":"13","author":"Riley","year":"2012","journal-title":"Aaps Pharmscitech"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1021\/acs.molpharmaceut.8b01200","article-title":"Use of PBPK modeling to evaluate the performance of dissolv it, a biorelevant dissolution assay for orally inhaled drug products","volume":"16","author":"Hassoun","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Saha, T., Sinha, S., Harfoot, R., Qui\u00f1ones-Mateu, M.E., and Das, S.C. (2022). Manipulation of Spray-Drying Conditions to Develop an Inhalable Ivermectin Dry Powder. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14071432"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Rojewska, M., Smu\u0142ek, W., Kaczorek, E., and Prochaska, K. (2021). Langmuir Monolayer Techniques for the Investigation of Model Bacterial Membranes and Antibiotic Biodegradation Mechanisms. Membranes, 11.","DOI":"10.3390\/membranes11090707"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.ejpb.2019.05.022","article-title":"In vitro investigation on the impact of airway mucus on drug dissolution and absorption at the air-epithelium interface in the lungs","volume":"141","author":"Cingolani","year":"2019","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3053","DOI":"10.1021\/acs.molpharmaceut.9b00289","article-title":"Pulmonary dissolution of poorly soluble compounds studied in an ex vivo rat lung model","volume":"16","author":"Eriksson","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejpb.2021.02.011","article-title":"Pharmacokinetics of rifampicin after repeated intra-tracheal administration of amorphous and crystalline powder formulations to Sprague Dawley rats","volume":"162","author":"Khadka","year":"2021","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2642","DOI":"10.1021\/acs.molpharmaceut.5b00046","article-title":"Pharmacokinetics of inhaled rifampicin porous particles for tuberculosis treatment: Insight into rifampicin absorption from the lungs of guinea pigs","volume":"12","author":"Sung","year":"2015","journal-title":"Mol. Pharm."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"9763","DOI":"10.1073\/pnas.0403235101","article-title":"Pulmonary delivery of an erythropoietin Fc fusion protein in non-human primates through an immunoglobulin transport pathway","volume":"101","author":"Bitonti","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1093\/jac\/dki461","article-title":"Pharmacokinetics of inhaled colistin in patients with cystic fibrosis","volume":"57","author":"Ratjen","year":"2006","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.addr.2020.07.025","article-title":"In vitro, ex vivo and in vivo methods of lung absorption for inhaled drugs","volume":"161\u2013162","author":"Sakagami","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/j.addr.2006.07.012","article-title":"In vivo, in vitro and ex vivo models to assess pulmonary absorption and disposition of inhaled therapeutics for systemic delivery","volume":"58","author":"Sakagami","year":"2006","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.ejps.2013.06.004","article-title":"In vitro, in vivo and ex vivo models for studying particle deposition and drug absorption of inhaled pharmaceuticals","volume":"49","author":"Nahar","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ijpharm.2018.11.072","article-title":"Searching for physiologically relevant in vitro dissolution techniques for orally inhaled drugs","volume":"556","author":"Radivojev","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.jconrel.2011.07.039","article-title":"A strategy to deliver genes to cystic fibrosis lungs: A battle with environment","volume":"155","author":"Ibrahim","year":"2011","journal-title":"J. Control. 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