Delivery of Dry Powders to the Lungs: Influence of Particle Attributes from a Biological and Technological Point of View

Page: [180 - 194] Pages: 15

  • * (Excluding Mailing and Handling)

Abstract

Dry powder inhalers are medical devices used to deliver powder formulations of active pharmaceutical ingredients via oral inhalation to the lungs. Drug particles, from a biological perspective, should reach the targeted site, dissolve and permeate through the epithelial cell layer in order to deliver a therapeutic effect. However, drug particle attributes that lead to a biological activity are not always consistent with the technical requirements necessary for formulation design. For example, small cohesive drug particles may interact with neighbouring particles, resulting in large aggregates or even agglomerates that show poor flowability, solubility and permeability. To circumvent these hurdles, most dry powder inhalers currently on the market are carrier-based formulations. These formulations comprise drug particles, which are blended with larger carrier particles that need to detach again from the carrier during inhalation. Apart from blending process parameters, inhaler type used and patient’s inspiratory force, drug detachment strongly depends on the drug and carrier particle characteristics such as size, shape, solid-state and morphology as well as their interdependency. This review discusses critical particle characteristics. We consider size of the drug (1-5 µm in order to reach the lung), solid-state (crystalline to guarantee stability versus amorphous to improve dissolution), shape (spherical drug particles to avoid macrophage clearance) and surface morphology of the carrier (regular shaped smooth or nano-rough carrier surfaces for improved drug detachment.) that need to be considered in dry powder inhaler development taking into account the lung as biological barrier.

Keywords: Dry powder inhaler (DPI), drug particle attributes, lung biology, carrier characteristics, particle interactions, clearance mechanism.

Graphical Abstract

[1]
Ashurst, I.; Malton, A.; Prime, D.; Sumby, B. Latest advances in the development of dry powder inhalers. Pharm. Sci. Technol. Today, 2000, 3(7), 246-256.
[2]
Alagusundaram, M.; Deepthi, N.; Ramkanth, S.; Angalaparameswari, S.; Saleem, T.S.M.; Gnanaprakash, K.; Thiruvengadarajan, V.S.; Chetty, C.M. Dry Powder inhalers: An overview. Int. J. Res. Pharm. Sci, 2010, 1(1), 34-42.
[3]
Begat, P.; Morton, D.A.V.; Staniforth, J.N.; Price, R. The cohesive-adhesive balances in dry powder inhaler formulations II: Influence on fine particle delivery characteristics. Pharm. Res., 2004, 21(10), 1826-1833.
[4]
de Boer, A.H. Optimisation of dry powder inhalation; Reijksuniversiteit Groningen, 2005, pp. 273-277.
[5]
de Boer, A.H.; Hagedoorn, P.; Hoppentocht, M.; Buttini, F.; Grasmeijer, F.; Frijlink, H.W. Dry powder inhalation: Past, present and future. Expert Opin. Drug Deliv., 2017, 14(4), 499-512.
[6]
Hoppentocht, M.; Hagedoorn, P.; Frijlink, H.W.; de Boer, A.H. Technological and practical challenges of dry powder inhalers and formulations. Adv. Drug Deliv. Rev., 2014, 18-31.
[7]
Mehta, P. Dry powder inhalers: A focus on advancements in novel drug delivery systems. J. Drug Deliv., 2016, 2016, 1-17.
[8]
Hare, J.I.; Lammers, T.; Ashford, M.B.; Puri, S.; Storm, G.; Barry, S.T. Challenges and Strategies in anti-cancer nanomedicine development: An industry perspective. Adv. Drug Deliv. Rev., 2017, 108, 25-38.
[9]
Johnstone, T.C.; Suntharalingam, K.; Lippard, S.J. The next generation of platinum drugs: Targeted pt(II) agents, nanoparticle delivery, and pt(iv) prodrugs. Chem. Rev., 2016, 116(5), 3436-3486.
[10]
Smola, M.; Vandamme, T.; Sokolowski, A. Nanocarriers as pulmonary drug delivery systems to treat and to diagnose respiratory and non respiratory diseases. Int. J. Nanomedicine, 2008, 3(1), 1-19.
[11]
Komiyama, M.; Yoshimoto, K.; Sisido, M.; Ariga, K. Chemistry can make strict and fuzzy controls for bio-systems: DNA nanoarchitectonics and cell-macromolecular nanoarchitectonics. Bull. Chem. Soc. Jpn., 2017, 90(9), 967-1004.
[12]
Jain, S.; Patel, N.; Shah, M.K.; Khatri, P.; Vora, N. Recent advances in lipid-based vesicles and particulate carriers for topical and transdermal application. J. Pharm. Sci., 2017, 106(2), 423-445.
[13]
Brunaugh, A.D.; Smyth, H.D.C. Formulation techniques for high dose dry powders. Int. J. Pharm., 2018, 547(1-2), 489-498.
[14]
Peng, T.; Lin, S.; Niu, B.; Wang, X.; Huang, Y.; Zhang, X.; Li, G.; Pan, X.; Wu, C. Influence of physical properties of carrier on the performance of dry powder inhalers. Acta Pharm. Sin. B, 2016, 6(4), 308-318.
[15]
Cun, D.; Wan, F.; Yang, M. Formulation strategies and particle engineering technologies for pulmonary delivery of biopharma-ceuticals. Curr. Pharm. Des., 2015, 21(19), 2599-2610.
[16]
Lin, Y.W.; Wong, J.; Qu, L.; Chan, H.K.; Zhou, Q. (Tony). Powder production and particle engineering for dry powder inhaler formulations. Curr. Pharm. Des., 2015, 21(27), 3902-3916.
[17]
Franks, T.J.; Colby, T.V.; Travis, W.D.; Tuder, R.M.; Reynolds, H.Y.; Brody, A.R.; Cardoso, W.V.; Crystal, R.G.; Drake, C.J.; Engelhardt, J.; Frid, M.; Herzog, E.; Mason, R.; Phan, S.H.; Randell, S.H.; Rose, M.C.; Stevens, T.; Serge, J.; Sunday, M.E.; Voynow, J.A.; Weinstein, B.M.; Whitsett, J.; Williams, M.C. Resident cellular components of the human lung: Current knowledge and goals for research on cell phenotyping and function. Proc. Am. Thorac. Soc., 2008, 5(7), 763-766.
[18]
Pocock, G.; Richards, C.D.; Richards, D. Introduction to the respiratory system.Human Physiology; Oxford University Press: Oxford, 2013, pp. 451-491.
[19]
Beckett, W.S.; Nordberg, G.F.; Clarkson, T.W. Routes of exposure, dose, and metabolism of metals.Handbook on the Toxicology of Metals; Nordberg, G.F.; Fowler, B.A.; Nordberg, M.; Friberg, L.T., Eds.; Academic Press: Burlington, 2007, pp. 39-64.
[20]
Heyder, J. Deposition of inhaled particles in the human respiratory tract and consequences for regional targeting in respiratory drug delivery. Proc. Am. Thorac. Soc., 2004, 1(4), 315-320.
[21]
Tena, A.F.; Clará, P.C. Deposition of inhaled particles in lungs. Arch. Bronconeumol., 2012, 48(7), 240-246.
[22]
Li, Z.; Kleinstreuer, C.; Zhang, Z. Particle deposition in the human tracheobronchial airways due to transient inspiratory flow patterns. J. Aerosol Sci., 2007, 38(6), 625-644.
[23]
Traini, D. Inhalation drug delivery. In: Inhalation Drug Delivery - Techniques and Products; Traini, D.; Colombo, G.; Young, P.M.; Eds.; Wiley Blackwell, 2013; p. 1-15.
[24]
Fröhlich, E.; Mercuri, A.; Wu, S.; Salar-Behzadi, S. Measurements of deposition, lung surface area and lung fluid for simulation of inhaled compounds. Front. Pharmacol., 2016, 7, 181.
[25]
Ng, A.W.; Bidani, A.; Heming, T.A. Innate host defense of the lung: Effects of lung-lining fluid pH. Lung, 2004, 182(5), 297-317.
[26]
Bocci, V. The potential toxicity of ozone: Side effects and contraindications of ozonetherapy.Ozone: A new medical drug; Springer Netherlands: Dordrecht, 2011, pp. 75-84.
[27]
Olsson, B.; Bondesson, E.; Borgström, L.; Edsbäcker, S.; Eirefelt, S.; Ekelund, K.; Gustavsson, L.; Hegelund-Myrbäck, T. Pulmonary drug metabolism, clearance, and absorption.Controlled Pulmonary Drug Delivery; Smyth, H.D.C.; Hickey, A.J., Eds.; Springer New York: New York, NY, 2011, pp. 21-50.
[28]
Patton, J.S. Mechanisms of macromolecule absorption by the lungs. Adv. Drug Deliv. Rev., 1996, 19(1), 3-36.
[29]
Fröhlich, E.; Roblegg, E. Mucus as physiological barrier to intracellular delivery.Intracellular Delivery II: Fundamentals and Applications; Springer Netherlands: Dordrecht, 2014, pp. 139-163.
[30]
Knowles, M.R.; Boucher, R.C. Mucus clearance as a primary innate defense mechanism for mammalian airways. J. Clin. Invest., 2002, 109(5), 571-577.
[31]
Parra, E.; Pérez-Gil, J. Composition, structure and mechanical properties define performance of pulmonary surfactant membranes and films. Chem. Phys. Lipids, 2015, 185, 153-175.
[32]
Fröhlich, E. Toxicity of orally inhaled drug formulations at the alveolar barrier: Parameters for initial biological screening. Drug Deliv., 2017, 24(1), 891-905.
[33]
Das, S.C.; Stewart, P.J. The influence of lung surfactant liquid crystalline nanostructures on respiratory drug delivery. Int. J. Pharm., 2016, 514(2), 465-474.
[34]
Wiedmann, T.S.; Bhatia, R.; Wattenberg, L.W. Drug solubilization in lung surfactant. J. Control. Release, 2000, 65(1-2), 43-47.
[35]
McAllister, S.M.; Alpar, H.O.; Teitelbaum, Z.; Bennett, D.B. Do interactions with phospholipids contribute to the prolonged retention of polypeptides within the lung? Adv. Drug Deliv. Rev., 1996, 19(1), 89-110.
[36]
Rokicki, W.; Rokicki, M.; Wojtacha, J.; Dżeljijli, A. The role and importance of club cells (clara cells) in the pathogenesis of some respiratory diseases. Kardiochir. Torakochirurgia Pol., 2016, 13(1), 26-30.
[37]
Donovan, M.D. Effect of route of administration and distribution on drug action. In: Modern Pharmaceutics Volume 1: Basic Principles and Systems; Florence, A.T.; Siepmann, J., Eds.; CRC Press: Boca Raton, 2010; p. 117-154.
[38]
Andrade, F.; Albuquerque, J.; Nascimento, A.V. Cell-based in vitro models for pulmonary permeability studies.Concepts and models for drug permeability studies; Sarmento, B., Ed.; Woodhead Publishing, 2015, p. 408.
[39]
Patton, J.; Fishburn, C.; Weers, J. The lungs as a portal of entry for systemic drug delivery. Proc. Am. Thorac. Soc., 2004, 1(4), 338-344.
[40]
Berg, M.M.; Kim, K.J.; Lubman, R.L.; Crandall, E.D. Hydrophilic solute transport across rat alveolar epithelium. J. Appl. Physiol., 1989, 66(5), 2320-2327.
[41]
Conhaim, R.L.; Eaton, A.; Staub, N.C.; Heath, T.D. Equivalent pore estimate for the alveolar-airway barrier in isolated dog lung. J. Appl. Physiol., 1988, 64(3), 1134-1142.
[42]
Volk, C. OCTs, OATs, and OCTNs: Structure and function of the polyspecific organic ion transporters of the SLC22 family. Wiley Interdisciplinary. Reviews: Membrane Transport and Signaling., 2014, 3(1), 1-13.
[43]
Horvath, G.; Schmid, N.; Fragoso, M.A.; Schmid, A.; Conner, G.E.; Salathe, M.; Wanner, A. Epithelial organic cation transporters ensure pH-dependent drug absorption in the airway. Am. J. Respir. Cell Mol. Biol., 2007, 36(1), 53-60.
[44]
Groneberg, D.A.; Fischer, A.; Chung, K.F.; Daniel, H. Molecular mechanisms of pulmonary peptidomimetic drug and peptide transport. Am. J. Respir. Cell Mol. Biol., 2004, 251-260.
[45]
van der Deen, M.; de Vries, E.G.E.; Timens, W.; Scheper, R.J.; Timmer-Bosscha, H.; Postma, D.S. ATP-Binding Cassette (ABC) transporters in normal and pathological lung. Respir. Res., 2005, 6(1), 59.
[46]
Scheffer, G.L.; Pijnenborg, A.C.L.M.; Smit, E.F.; Müller, M.; Postma, D.S.; Timens, W.; van der Valk, P.; de Vries, E.G.E.; Scheper, R.J. Multidrug resistance related molecules in human and murine lung. J. Clin. Pathol., 2002, 55(5), 332-339.
[47]
Johnson, L.G.; Boucher, R.C. Macromolecular transport across nasal and respiratory epithelia.In Biological Barriers to Protein Delivery; Audus, K.L.; Raub, T.J., Eds.; Springer US: Boston, MA, 1993, pp. 161-178.
[48]
Gumbleton, M. Caveolae as potential macromolecule trafficking compartments within alveolar epithelium. Adv. Drug Deliv. Rev., 2001, 49(3), 281-300.
[49]
Salathé, M.; O’Riordan, T.; Wanner, A. Mucociliary clearance.In The Lung: Scientific Foundations; Crystal, R.G.; West, J.B., Eds.; Lippincott-Raven Publishers: Philadelphia, 1997, pp. 2295-2308.
[50]
Riley, T.; Christopher, D.; Arp, J.; Casazza, A.; Colombani, A.; Cooper, A.; Dey, M.; Maas, J.; Mitchell, J.; Reiners, M. Challenges with developing in vitro dissolution tests for orally inhaled products (OIPs). AAPS PharmSciTech, 2012, 13(3), 978-989.
[51]
Higham, A.; Lea, S.; Mason, S.; Singh, D. Macrophages, corticosteroids and COPD: What do we know? Macrophage, 2016, 3, e1262.
[52]
Lay, J.C.; Alexis, N.E.; Zeman, K.L.; Peden, D.B.; Bennett, W.D. In vivo uptake of inhaled particles by airway phagocytes is enhanced in patients with mild asthma compared with normal volunteers. Thorax, 2009, 64(4), 313-320.
[53]
Lay, J.C.; Bennett, W.D.; Kim, C.S.; Devlin, R.B.; Bromberg, P.A. Retention and intracellular distribution of instilled iron oxide particles in human alveolar macrophages. Am. J. Respir. Cell Mol. Biol., 1998, 18(5), 687-695.
[54]
Kumar, A.; Bicer, E.M.; Morgan, A.B.; Pfeffer, P.E.; Monopoli, M.; Dawson, K.A.; Eriksson, J.; Edwards, K.; Lynham, S.; Arno, M.; Behndig, A.F.; Blomberg, A.; Somers, G.; Hassall, D.; Dailey, L.A.; Forbes, B.; Mudway, I.S. Enrichment of immunoregulatory proteins in the biomolecular corona of nanoparticles within human respiratory tract lining fluid. Nanomed. Nanotechnol. Biol. Med., 2016, 12(4), 1033-1043.
[55]
Schürch, S.; Geiser, M.; Lee, M.M.; Gehr, P. Particles at the airway interfaces of the lung. Colloids surfaces. B Biointerfaces, 1999, 15(3-4), 339-353.
[56]
Murgia, X.; Pawelzyk, P.; Schaefer, U.F.; Wagner, C.; Willenbacher, N.; Lehr, C.M. Size-limited penetration of nanoparticles into porcine respiratory mucus after aerosol deposition. Biomacromolecules, 2016, 17(4), 1536-1542.
[57]
Wauthoz, N.; Amighi, K. Formulation strategies for pulmonary delivery of poorly soluble drugs.Pulmonary Drug Delivery; John Wiley & Sons, Ltd, 2015, pp. 87-122.
[58]
Son, Y.J.; Horng, M.; Copley, M.; McConville, J.T. Optimization of an in vitro dissolution test method for inhalation formulations. Dissolut. Technol., 2010, 17(2), 6-13.
[59]
May, S.; Jensen, B.; Weiler, C.; Wolkenhauer, M.; Schneider, M.; Lehr, C.M. Dissolution testing of powders for inhalation: Influence of particle deposition and modeling of dissolution profiles. Pharm. Res., 2014, 31(11), 3211-3224.
[60]
Davies, N.M.; Feddah, M.R. A novel method for assessing dissolution of aerosol inhaler products. Int. J. Pharm., 2003, 255(1-2), 175-187.
[61]
Theodorou, I.G.; Ruenraroengsak, P.; Gow, A.; Schwander, S.; Zhang, J. (Jim); Chung, K.F.; Tetley, T.D.; Ryan, M.P.; Porter, A.E. Effect of pulmonary surfactant on the dissolution, stability and uptake of zinc oxide nanowires by human respiratory epithelial cells. Nanotoxicology, 2016, 10(9), 1351-1362.
[62]
Claudia, M.; Kristin, Ö.; Jennifer, O.; Eva, R.; Eleonore, F. Comparison of fluorescence-based methods to determine nanoparticle uptake by phagocytes and non-phagocytic cells in vitro. Toxicology, 2017, 378, 25-36.
[63]
Sweeney, S.; Theodorou, I.G.; Zambianchi, M.; Chen, S.; Gow, A.; Schwander, S.; Zhang, J.J.; Chung, K.F.; Shaffer, M.S.P.; Ryan, M.P. Silver nanowire interactions with primary human alveolar type-ii epithelial cell secretions: Contrasting bioreactivity with human alveolar type-i and type-ii epithelial cells. Nanoscale, 2015, 7(23), 10398-10409.
[64]
Kasper, J.Y.; Feiden, L.; Hermanns, M.I.; Bantz, C.; Maskos, M.; Unger, R.E.; Kirkpatrick, C.J. Pulmonary surfactant augments cytotoxicity of silica nanoparticles: Studies on an in vitro air-blood barrier model. Beilstein J. Nanotechnol., 2015, 6(1), 517-528.
[65]
Walsh, B. Section III therapeutic procedures for treatment of neonatal and pediatric disorders. In: Neonatal and Pediatric Respiratory Care; Walsh, B., Ed.; Elsevier: St. Louis, 2015; p. 245-266.
[66]
Griese, M. Pulmonary surfactant in health and human lung diseases: State of the art. Eur. Respir. J., 1999, 13(6), 1455-1476.
[67]
van der Vliet, A.; O’Neill, C.A.; Cross, C.E.; Koostra, J.M.; Volz, W.G.; Halliwell, B.; Louie, S. Determination of low-molecular-mass antioxidant concentrations in human respiratory tract lining fluids. Am. J. Physiol., 1999, 276, L289-L296.
[68]
Witham, C.; Phillips, E. Spiros inhaler technology.In Modified-Release Drug Delivery Technology; Rathbone, M.J.; Hadgraft, J.; Roberts, M.S., Eds.; Marcel Dekker, Inc.: New York, 2002, pp. 913-925.
[69]
Laube, B.L.; Benedict, G.W.; Dobs, A.S. Time to peak insulin level, relative bioavailability, and effect of site of deposition of nebulized insulin in patients with noninsulin-dependent diabetes mellitus. J. Aerosol Med., 1998, 11(3), 153-173.
[70]
Islam, N.; Gladki, E. Dry Powder inhalers (DPIs)--a Review of device reliability and innovation. Int. J. Pharm., 2008, 360(1-2), 1-11.
[71]
Labiris, N.R.; Dolovich, M.B. Pulmonary drug delivery. Part I: Physiological factors affecting therapeutic effectiveness of aerosolized medications. Br. J. Clin. Pharmacol., 2003, 56(6), 588-599.
[72]
Colthorpe, P.; Farr, S.J.; Taylor, G. Smith, lan J.; Wyatt, D. The pharmacokinetics of pulmonary-delivered insulin: A comparison of intratracheal and aerosol administration to the rabbit. Pharm. Res. An Off. J. Am. Assoc. Pharm. Sci., 1992, 9(6), 764-768.
[73]
Blagden, N.; de Matas, M.; Gavan, P.T.; York, P. Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates. Adv. Drug Deliv. Rev., 2007, 59(7), 617-630.
[74]
Savjani, K.T.; Gajjar, A.K.; Savjani, J.K. Drug solubility: Importance and enhancement techniques. ISRN Pharm., 2012, 2012, 1-10.
[75]
Babu, V.R.; Areefulla, S.H.; Mallikarjun, V. Solubility and dissolution enhancement: An overview. J. Pharm. Res., 2010, 3(1), 141-145.
[76]
Vemula, V.R.; Lagishetty, V.; Lingala, S. Solubility enhancement techniques. Int. J. Pharm. Sci. Rev. Res., 2010, 5(1), 41-51.
[77]
Sun, J.; Wang, F.; Sui, Y.; She, Z.; Zhai, W.; Wang, C.; Deng, Y. Effect of particle size on solubility, dissolution rate, and oral bioavailability: Evaluation using coenzyme Q10 as naked nanocrystals. Int. J. Nanomedicine, 2012, 7, 5733-5744.
[78]
Tolman, J.A.; Williams, R.O. Advances in the pulmonary delivery of poorly water-soluble drugs: Influence of solubilization on pharmacokinetic properties. Drug Dev. Ind. Pharm., 2010, 36(1), 1-30.
[79]
Haghi, M.; Traini, D.; Bebawy, M.; Young, P.M. Deposition, diffusion and transport mechanism of dry powder microparticulate salbutamol, at the respiratory epithelia. Mol. Pharm., 2012, 9(6), 1717-1726.
[80]
Haghi, M.; Traini, D.; Young, P. In vitro cell integrated impactor deposition methodology for the study of aerodynamically relevant size fractions from commercial pressurised metered dose inhalers. Pharm. Res., 2014, 31(7), 1779-1787.
[81]
Chen, L.; Okuda, T.; Lu, X.Y.; Chan, H.K. Amorphous powders for inhalation drug delivery. Adv. Drug Deliv. Rev., 2015, 100, 102-115.
[82]
Wang, Y-B.; Watts, A.B.; Peters, J.I.; Liu, S.; Batra, A.; Williams, R.O. In vitro and in vivo performance of dry powder inhalation formulations: comparison of particles prepared by thin film freezing and micronization. AAPS PharmSciTech, 2014, 15(4), 981-993.
[83]
Scalia, S.; Haghi, M.; Losi, V.; Trotta, V.; Young, P.M.; Traini, D. Quercetin solid lipid microparticles: A flavonoid for inhalation lung delivery. Eur. J. Pharm. Sci., 2013, 49(2), 278-285.
[84]
Ong, H.X.; Traini, D.; Salama, R.; Anderson, S.D.; Daviskas, E.; Young, P.M. The effects of mannitol on the transport of ciprofloxacin across respiratory epithelia. Mol. Pharm., 2013, 10(8), 2915-2924.
[85]
Ong, H.X.; Traini, D.; Bebawy, M.; Young, P.M. Epithelial profiling of antibiotic controlled release respiratory formulations. Pharm. Res., 2011, 28(9), 2327-2338.
[86]
Mosharraf, M.; Nystrom, C. The effect of particle-size and shape on the surface specific dissolution rate of microsized practically insoluble drugs. Int. J. Pharm., 1995, 122(1-2), 35-47.
[87]
Champion, J.A.; Mitragotri, S. Role of target geometry in phagocytosis. Proc. Natl. Acad. Sci. USA, 2006, 103(13), 4930-4934.
[88]
Champion, J.A.; Katare, Y.K.; Mitragotri, S. Particle shape: A new design parameter for micro- and nanoscale drug delivery carriers. J. Control. Release, 2014, 121, 3-9.
[89]
Champion, J.A.; Mitragotri, S. Shape induced inhibition of phagocytosis of polymer particles. Pharm. Res., 2009, 26(1), 244-249.
[90]
Doshi, N.; Mitragotri, S. Macrophages recognize size and shape of their targets. PLoS One, 2010, 5(4), 1-6.
[91]
Paul, D.; Achouri, S.; Yoon, Y.; Herre, J.; Bryant, C.E.; Cicuta, P. Phagocytosis dynamics depends on target shape. Biophys. J., 2013, 105(5), 1143-1150.
[92]
Geiser, M.; Schurch, S.; Gehr, P. Influence of surface chemistry and topography of particles on their immersion into the lung’s surface-lining layer. J. Appl. Physiol., 2003, 94(5), 1793-1801.
[93]
Gerber, P.J.; Lehmann, C.; Gehr, P.; Schürch, S. Wetting and spreading of a surfactant film on solid particles: Influence of sharp edges and surface irregularities. Langmuir, 2006, 22(12), 5273-5281.
[94]
Khranovskyy, V.; Ekblad, T.; Yakimova, R.; Hultman, L. Surface morphology effects on the light- controlled wettability of ZnO nanostructures surface morphology effects on the light-controlled wettability. Appl. Surf. Sci., 2012, 258, 8146-8152.
[95]
Faulhammer, E.; Fink, M.; Llusa, M.; Lawrence, S.M.; Biserni, S.; Calzolari, V.; Khinast, J.G. Low-dose capsule filling of inhalation products: Critical material attributes and process parameters. Int. J. Pharm., 2014, 473(1-2), 617-626.
[96]
Chow, A.H.L.; Tong, H.H.Y.; Chattopadhyay, P.; Shekunov, B.Y. Particle engineering for pulmonary drug delivery. Pharm. Res., 2007, 24(3), 411-437.
[97]
Zhang, G.G.Z.; Law, D.; Schmitt, E.A.; Qiu, Y.H. Phase transformation considerations during process development and manufacture of solid oral dosage forms. Adv. Drug Deliv. Rev., 2004, 56(3), 371-390.
[98]
Newman, A.; Zografi, G. Critical considerations for the qualitative and quantitative determination of process‐induced disorder in crystalline solids. J. Pharm. Sci., 2014, 103(9), 2595-2604.
[99]
Priemel, P.A.; Grohganz, H.; Rades, T. Unintended and in Situ amorphisation of pharmaceuticals. Adv. Drug Deliv. Rev., 2016, 100, 126-132.
[100]
Aaltonen, J.; Rades, T. Towards physico-relevant dissolution testing: The importance of solid-state analysis in dissolution. Dissolut. Technol., 2009, 16(2), 47-54.
[101]
Wong, J.; Kwok, P.C.L.; Noakes, T.; Fathi, A.; Dehghani, F.; Chan, H.K. Effect of crystallinity on electrostatic charging in dry powder inhaler formulations. Pharm. Res., 2014, 31(7), 1656-1664.
[102]
Muhammad, S.A.F.; Langrish, T.; Tang, P.; Adi, H.; Chan, H.K.; Kazarian, S.G.; Dehghani, F. A novel method for the production of crystalline micronised particles. Int. J. Pharm., 2010, 388(1-2), 114-122.
[103]
Faulhammer, E.; Zellnitz, S.; Wutscher, T.; Stranzinger, S.; Zimmer, A.; Paudel, A. Performance indicators for carrier-based DPIs : Carrier surface properties for capsule Fi Lling and API properties for in vitro aerosolisation. Int. J. Pharm., 2018, 536(1), 326-335.
[104]
Crowder, T.M.; Rosati, J.A.; Schroeter, J.D.; Hickey, A.J.; Martonen, T.B. Fundamental effects of particle morphology on lung delivery: Predictions of stokes’ law and the particular relevance to dry powder inhaler formulation and development. Pharm. Res., 2002, 19(3), 239-245.
[105]
Larhrib, H.; Martin, G.P.; Marriott, C.; Prime, D. the influence of carrier and drug morphology on drug delivery from dry powder formulations. Int. J. Pharm., 2003, 257(1-2), 283-296.
[106]
Pinto, J.T.; Radivojev, S.; Zellnitz, S.; Roblegg, E.; Paudel, A. How does secondary processing affect the physicochemical properties of inhalable salbutamol sulphate particles? A temporal investigation. Int. J. Pharm., 2017, 528(1-2), 416-428.
[107]
Faulhammer, E.; Wahl, V.; Zellnitz, S.; Khinast, J.G.; Paudel, A. carrier-based dry powder inhalation: Impact of carrier modification on capsule filling processability and in vitro aerodynamic performance. Int. J. Pharm., 2015, 491(1-2), 231-242.
[108]
Columbano, A.; Buckton, G.; Wikeley, P. A study of the crystallisation of amorphous salbutamol sulphate using water vapour sorption and near infrared spectroscopy. Int. J. Pharm., 2002, 237(1-2), 171-178.
[109]
Zellnitz, S.; Narygina, O.; Resch, C.; Schroettner, H.; Urbanetz, N.A. Crystallization speed of salbutamol as a function of relative humidity and temperature. Int. J. Pharm., 2015, 489(1-2), 170-176.
[110]
Steckel, H.; Bolzen, N. Alternative sugars as potential carriers for dry powder inhalations. Int. J. Pharm., 2004, 270(1-2), 297-306.
[111]
Rahimpour, Y.; Hamishehkar, H. Lactose engineering for better performance in dry powder inhalers. Adv. Pharm. Bull., 2012, 2(2), 183-187.
[112]
Kaialy, W.; Alhalaweh, A.; Velaga, S.P.; Nokhodchi, A. Influence of lactose carrier particle size on the aerosol performance of budesonide from a dry powder inhaler. Powder Technol., 2012, 227, 74-85.
[113]
Steckel, H.; Mu, B.W. In vitro evaluation of dry powder inhalers II : Influence of carrier particle size and concentration on in vitro deposition. Int. J. Pharm., 1997, 154, 31-37.
[114]
Louey, M.D.; Razia, S.; Stewart, P.J. Influence of physico-chemical carrier properties on the in vitro aerosol deposition from interactive mixtures. Int. J. Pharm., 2003, 252(1-2), 87-98.
[115]
Kawashima, Y.; Serigano, T.; Hino, T.; Yamamoto, H.; Takeuchi, H. Effect of surface morphology of carrier lactose on dry powder inhalation property of pranlukast hydrate. Int. J. Pharm., 1998, 172(1-2), 179-188.
[116]
Dickhoff, B.H.J.; de Boer, A.H.; Lambregts, D.; Frijlink, H.W. The effect of carrier surface and bulk properties on drug particle detachment from crystalline lactose carrier particles during inhalation, as function of carrier payload and mixing time. Eur. J. Pharm. Biopharm., 2003, 56(2), 291-302.
[117]
Donovan, M.J.; Smyth, H.D.C. Influence of size and surface roughness of large lactose carrier particles in dry powder inhaler formulations. Int. J. Pharm., 2010, 402(1-2), 1-9.
[118]
Zeng, X.M.; Martin, G.P.; Marriott, C.; Pritchard, J. the effects of carrier size and morphology on the dispersion of salbutamol sulphate after aerosolization at different flow rates. J. Pharm. Pharmacol., 2000, 52(10), 1211-1221.
[119]
de Boer, A.H.; Chan, H.K.; Price, R. A critical view on lactose-based drug formulation and device studies for dry powder inhalation: Which are relevant and what interactions to expect? Adv. Drug Deliv. Rev., 2012, 257-274.
[120]
Tee, S.K.; Marriott, C.; Zeng, X.M.; Martin, G.P. The use of different sugars as fine and coarse carriers for aerosolised salbutamol sulphate. Int. J. Pharm., 2000, 208(1-2), 111-123.
[121]
Islam, N.; Stewart, P.; Larson, I.; Hartley, P. Effect of carrier size on the dispersion of salmeterol xinafoate from interactive mixtures. J. Pharm. Sci., 2004, 93(4), 1030-1038.
[122]
Jones, M.D.; Price, R. The influence of fine excipient particles on the performance of carrier-based dry powder inhalation formulations. Pharm. Res., 2006, 23(8), 1665-1674.
[123]
Guenette, E.; Barrett, A.; Kraus, D.; Brody, R.; Harding, L.; Magee, G. Understanding the effect of lactose particle size on the properties of DPI formulations using experimental design. Int. J. Pharm., 2009, 380(1-2), 80-88.
[124]
Thalberg, K.; Berg, E.; Fransson, M. Modeling dispersion of dry powders for inhalation. The concepts of total fines, cohesive energy and interaction parameters. Int. J. Pharm., 2012, 427(2), 224-233.
[125]
Grasmeijer, F.; Lexmond, A.J.; van Den Noort, M.; Hagedoorn, P.; Hickey, A.J.; Frijlink, H.W.; de Boer, A.H. New mechanisms to explain the effects of added lactose fines on the dispersion performance of adhesive mixtures for inhalation. PLoS One, 2014, 9(1), e87825.
[126]
Grasmeijer, F.; Grasmeijer, N.; Hagedoorn, P.; Frijlink, H.W.; de Boer, A.H. Recent advances in the fundamental understanding of adhesive mixtures for inhalation. Curr. Pharm. Des., 2015, 21(40), 5900-5914.
[127]
Jones, M.D.; Santo, J.G.F.; Yakub, B.; Dennison, M.; Master, H.; Buckton, G. The relationship between drug concentration, mixing time, blending order and ternary dry powder inhalation performance. Int. J. Pharm., 2010, 391(1-2), 137-147.
[128]
Jones, M.D.; Hooton, J.C.; Dawson, M.L.; Ferrie, A.R.; Price, R. An investigation into the dispersion mechanisms of ternary dry powder inhaler formulations by the quantification of interparticulate forces. Pharm. Res., 2008, 25(2), 337-348.
[129]
Della Bella, A.; Salomi, E.; Buttini, F.; Bettini, R. The role of the solid state and physical properties of the carrier in adhesive mixtures for lung delivery. Expert Opin. Drug Deliv., 2018, 15(7), 665-674.
[130]
Pilcer, G.; Wauthoz, N.; Amighi, K. Lactose characteristics and the generation of the aerosol. Adv. Drug Deliv. Rev., 2012, 64(3), 233-256.
[131]
Traini, D.; Young, P.M.; Thielmann, F.; Acharya, M. the influence of lactose pseudopolymorphic form on salbutamol sulfate-lactose interactions in DPI formulations. Drug Dev. Ind. Pharm., 2008, 34(9), 992-1001.
[132]
Kaialy, W.; Alhalaweh, A.; Velaga, S.P.; Nokhodchi, A. Effect of carrier particle shape on dry powder inhaler performance. Int. J. Pharm., 2011, 421(1), 12-23.
[133]
Cares-Pacheco, M.G.; Vaca-Medina, G.; Calvet, R.; Espitalier, F.; Letourneau, J-J.; Rouilly, A.; Rodier, E. Physicochemical characterization of D-mannitol polymorphs: The challenging surface energy determination by inverse gas chromatography in the infinite dilution region. Int. J. Pharm., 2014, 475(1-2), 69-81.
[134]
Zeng, X.M.; Martin, G.P.; Marriott, C.; Pritchard, J. Lactose as a carrier in dry powder formulations: The influence of surface characteristics on drug delivery. J. Pharm. Sci., 2001, 90(9), 1424-1434.
[135]
Zeng, X.M.; Martin, G.P.; Marriott, C.; Pritchard, J. The influence of crystallization conditions on the morphology of lactose intended for use as a carrier for dry powder aerosols. J. Pharm. Pharmacol., 2000, 52(6), 633-643.
[136]
Pilcer, G.; Amighi, K. Formulation strategy and use of excipients in pulmonary drug delivery. Int. J. Pharm., 2010, 392(1-2), 1-19.
[137]
Das, D.; Wang, E.; Langrish, T.A.G. Solid-phase crystallization of spray-dried glucose powders: A perspective and comparison with lactose and sucrose. Adv. Powder Technol., 2014, 25(4), 1234-1239.
[138]
Wu, L.; Miao, X.; Shan, Z.; Huang, Y.; Li, L.; Pan, X.; Yao, Q.; Li, G.; Wu, C. Studies on the spray dried lactose as carrier for dry powder inhalation. Asian J. Pharm. Sci., 2014, 9(6), 336-341.
[139]
Maas, S.G.; Schaldach, G.; Littringer, E.M.; Mescher, A.; Griesser, U.J.; Braun, D.E.; Walzel, P.E.; Urbanetz, N.A. The impact of spray drying outlet temperature on the particle morphology of mannitol. Powder Technol., 2011, 213(1-3), 27-35.
[140]
Littringer, E.M.; Mescher, A.; Schroettner, H.; Achelis, L.; Walzel, P.; Urbanetz, N.A. Spray dried mannitol carrier particles with tailored surface properties- the influence of carrier surface roughness and shape. Eur. J. Pharm. Biopharm., 2012, 82(1), 194-204.
[141]
Iida, K.; Todo, H.; Okamoto, H.; Danjo, K.; Leuenberger, H. Preparation of dry powder inhalation with lactose carrier particles surface-coated using a wurster fluidized bed. Chem. Pharm. Bull., 2005, 53(4), 431-434.
[142]
Iida, K.; Hayakawa, Y.; Okamoto, H.; Danjo, K.; Leuenberger, H. Preparation of dry powder inhalation by surface treatment of lactose carrier particles. Chem. Pharm. Bull. (Tokyo), 2003, 51(1), 1-5.
[143]
Kaialy, W.; Nokhodchi, A. Freeze-dried mannitol for superior pulmonary drug delivery via dry powder inhaler. Pharm. Res., 2013, 30(2), 458-477.
[144]
Zeng, X.M.; Martin, G.P.; Marriott, C.; Pritchard, J. The influence of carrier morphology on drug delivery by dry powder inhalers. Int. J. Pharm., 2000, 200(1), 93-106.
[145]
Littringer, E.M.; Mescher, A.; Schroettner, H.; Achelis, L.; Walzel, P.; Urbanetz, N.A. Spray dried mannitol carrier particles with tailored surface properties - The influence of carrier surface roughness and shape. Eur. J. Pharm. Biopharm., 2012, 82(1), 194-204.
[146]
Kaialy, W.; Martin, G.P.; Larhrib, H.; Ticehurst, M.D.; Kolosionek, E.; Nokhodchi, A. The influence of physical properties and morphology of crystallised lactose on delivery of salbutamol sulphate from dry powder inhalers. Colloids Surf. B Biointerfaces, 2012, 89, 29-39.
[147]
Podczeck, F. The influence of particle size distribution and surface roughness of carrier particles on the in vitro properties of dry powder inhalations. Aerosol Sci. Technol., 1999, 31(4), 301-321.
[148]
Young, P.M.; Roberts, D.; Chiou, H.; Rae, W.; Chan, H-K.; Traini, D. Composite carriers improve the aerosolisation efficiency of drugs for respiratory delivery. J. Aerosol Sci., 2008, 39(1), 82-93.
[149]
Flament, M-P.; Leterme, P.; Gayot, A. The influence of carrier roughness on adhesion, content uniformity and the in vitro deposition of terbutaline sulphate from dry powder inhalers. Int. J. Pharm., 2004, 275(1-2), 201-209.
[150]
Kaialy, W.; Nokhodchi, A. Freeze-dried mannitol for superior pulmonary drug delivery via dry powder inhaler. Pharm. Res., 2013, 30(2), 458-477.
[151]
Shalash, A.O.; Molokhia, A.M.; Elsayed, M.M.A. Insights into the roles of carrier microstructure in adhesive/carrier-based dry powder inhalation mixtures: Carrier porosity and fine particle content. Eur. J. Pharm. Biopharm., 2015, 96, 291-303.
[152]
de Boer, A.H.; Hagedoorn, P.; Gjaltema, D.; Goede, J.; Frijlink, H. Air Classifier Technology (ACT) in dry powder inhalation part 1. introduction of a novel Force Distribution Concept (FDC) explaining the performance of a basic air classifier on adhesive mixtures. Int. J. Pharm., 2003, 260(2), 187-200.
[153]
Grasmeijer, F.; Hagedoorn, P.; Frijlink, H.W.; de Boer, A.H. Drug content effects on the dispersion performance of adhesive mixtures for inhalation. PLoS One, 2013, 8(8), e71339.
[154]
Frijlink, H.W.; de Boer, A.H. Dry powder inhalers for pulmonary drug delivery. Expert Opin. Drug Deliv., 2004, 1(1), 67-86.
[155]
Zellnitz, S.; Redlinger-Pohn, J.D.; Kappl, M.; Schroettner, H.; Urbanetz, N.A. Preparation and characterization of physically modified glass beads used as model carriers in dry powder inhalers. Int. J. Pharm., 2013, 447(1-2), 132-138.
[156]
Williams, D.R. Particle engineering in pharmaceutical solids processing: Surface energy considerations. Curr. Pharm. Des., 2015, 21, 2677-2694.
[157]
Jong, T.; Li, J.; Morton, D.A.V.; Zhou, Q. (Tony); Larson, I. Investigation of the changes in aerosolization behavior between the jet-milled and spray-dried colistin powders through surface energy characterization. J. Pharm. Sci., 2016, 105(3), 1156-1163.
[158]
Du, P.; Du, J.; Smyth, H.D.C. Evaluation of granulated lactose as a carrier for dry powder inhaler formulations 2: Effect of drugs and drug loading. J. Pharm. Sci., 2017, 106(1), 366-376.
[159]
Podczeck, F. Particle-Particle Adhesion in Pharmaceutical Powder Handling; Imperial College Press: London, 1998.
[160]
Begat, P.; Morton, D.A.V.; Staniforth, J.N.; Price, R. the cohesive-adhesive balances in dry powder inhaler formulations I: Direct quantification by atomic force microscopy. Pharm. Res., 2004, 21(9), 1591-1597.
[161]
Saleem, I.; Smyth, H.; Telko, M. Prediction of dry powder inhaler formulation performance from surface energetics and blending dynamics. Drug Dev. Ind. Pharm., 2008, 34, 1002-1010.
[162]
Wong, J.; Lin, Y.W.; Kwok, P.C.L.; Niemelä, V.; Crapper, J.; Chan, H.K. Measuring bipolar charge and mass distributions of powder aerosols by a novel tool (BOLAR). Mol. Pharm., 2015, 12(9), 3433-3440.
[163]
Karner, S. Urbanetz, Nora, A. The impact of electrostatic charge in pharmaceutical powders with specific focus on inhalation-powders. J. Aerosol Sci., 2011, 42(6), 428-445.
[164]
Le, V.N.P.; Hoang Thi, T.H.; Robins, E.; Flament, M.P. Dry powder inhalers: study of the parameters influencing adhesion and dispersion of fluticasone propionate. AAPS PharmSciTech, 2012, 13(2), 477-484.
[165]
Karner, S.; Littringer, E.M.; Urbanetz, N.A. Triboelectrics: The influence of particle surface roughness and shape on charge acquisition during aerosolization and the DPI performance. Powder Technol., 2014, 262, 22-29.
[166]
Kwek, J.W.; Heng, D.; Lee, S.H.; Ng, W.K.; Chan, H.K.; Adi, S.; Heng, J.; Tan, R.B.H. High speed imaging with electrostatic charge monitoring to track powder deagglomeration upon impact. J. Aerosol Sci., 2013, 65, 77-87.
[167]
Naik, S.; Mukherjee, R.; Chaudhuri, B. Triboelectrification: A review of experimental and mechanistic modeling approaches with a special focus on pharmaceutical powders. Int. J. Pharm., 2016, 510(1), 375-385.
[168]
Kaialy, W. A review of factors affecting electrostatic charging of pharmaceuticals and adhesive mixtures for inhalation. Int. J. Pharm., 2016, 503, 262-276.
[169]
Wong, J.; Chan, H-K.; Kwok, P.C.L. Electrostatics in pharmaceutical aerosols for inhalation. Ther. Deliv., 2013, 4(8), 981-1002.
[170]
Das, S.; Larson, I.; Young, P.; Stewart, P. agglomerate properties and dispersibility changes of salmeterol xinafoate from powders for inhalation after storage at high relative humidity. Eur. J. Pharm. Sci., 2009, 37(3-4), 442-450.
[171]
Zeng, X.M.; MacRitchie, H.B.; Marriott, C.; Martin, G.P. Humidity-induced changes of the aerodynamic properties of dry powder aerosol formulations containing different carriers. Int. J. Pharm., 2007, 333(1-2), 45-55.
[172]
Young, P.M.; 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. Pharm. Res., 2007, 24(5), 963-970.