In vitro and in vivo testing methods for respiratory drug delivery

Expert Opinion on Drug Delivery

Volumn 8, Issue 1, 2011, Pages 57-69

  Agu, Remigius U ^a   Ugwoke, Michael I ^b  

^a DALHOUSIE UNIVERSITY   (Canada)

^b NANOMI B V   (Netherlands)

Author keywords

Cell culture; Drug testing methods; in vitro; in vivo; Inhalation aerosol; Respiratory drug delivery

Indexed keywords

CORTICOSTEROID; DIPALMITOYLPHOSPHATIDYLCHOLINE; FLUORESCEIN ISOTHIOCYANATE; PROPELLANT; SALBUTAMOL;

AEROSOL; CRYSTAL STRUCTURE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DELIVERY SYSTEM; DRUG DIFFUSION; DRUG DISPOSITION; DRUG FORMULATION; DRUG INSTILLATION; DRUG PENETRATION; DRUG SOLUBILITY; FLOW RATE; GAMMA SCINTIGRAPHY; HUMAN; IN VITRO STUDY; IN VIVO STUDY; INCUBATOR; INHALATIONAL DRUG ADMINISTRATION; LASER DIFFRACTION; LIGHT SCATTERING; METERED DOSE INHALER; NEBULIZATION; PARTICLE SIZE; POSITRON EMISSION TOMOGRAPHY; POWDER INHALER; REVIEW; SINGLE PHOTON EMISSION COMPUTER TOMOGRAPHY; TIDAL VOLUME;

ADMINISTRATION, INHALATION; AEROSOLS; ANIMALS; DRUG DELIVERY SYSTEMS; DRUG DESIGN; HUMANS; PARTICLE SIZE; PHARMACEUTICAL PREPARATIONS; RESPIRATORY TRACT DISEASES; SOLUBILITY;

EID: 78650545991     PISSN: 17425247     EISSN: None     Source Type: Journal    
DOI: 10.1517/17425247.2011.543896     Document Type: Review

References (105)

1. Rubin BK. Air and soul: The science and application of aerosol therapy. Respir Care 2010;55(7):911-21
2. Takizawa H. Recent development of drug delivery systems for the treatment of asthma and related disorders. Rec Pat Inflamm Allergy Drug Discov 2009;3(3):232-9
3. Agu RU, Ugwoke MI, Armand M, et al. The lung as a route for systemic delivery of therapeutic proteins and peptides. Respir Res 2001;2(4):198-209 . A very good review on pulmonary delivery of peptides and proteins. (Pubitemid 34187927)
4. Shoyele SA. Controlling the release of proteins/peptides via the pulmonary route. Methods Mol Biol 2008;437:141-8
5. El-Sherbiny IM, McGill S, Smyth HD. Swellable microparticles as carriers for sustained pulmonary drug delivery. J Pharm Sci 2010;99(5):2343-56
6. Ari A, Fink JB. Factors affecting bronchodilator delivery in mechanically ventilated adults. Nurs Crit Care 2010;15(4):192-203
7. Newman SP. Aerosol deposition considerations in inhalation therapy. Chest 1985;88(Suppl):152s-60s
8. Labiris NR, Dolovich MB. Pulmonary drug delivery. Part I: Physiological factors affecting therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol 2003;56(6):588-99
9. Li YZ, Sun X, Gong T, et al. Inhalable microparticles as carriers for pulmonary delivery of thymopentin-loaded solid lipid nanoparticles. Pharm Res 2010;27(9):1977-86
10. Malik DK, Baboota S, Ahuja A, et al. Recent advances in protein and peptide drug delivery systems. Curr Drug Deliv 2007;4(2):141-51 (Pubitemid 46557490)
11. Fischer A, Stegemann J, Scheuch G, et al. Novel devices for individualized controlled inhalation can optimize aerosol therapy in efficacy, patient care and power of clinical trials. Eur J Med Res 2009;14(Suppl 4):71-7
12. Henkin RI. Inhaled insulin-intrapulmonary, intranasal, and other routes of administration: Mechanisms of action. Nutrition 2010;26(1):33-9
13. Bao D, Zhao Y. Building membrane emulsification into pulmonary drug delivery and targeting. Pharm Res 2010. [Epub ahead of print]
14. Newman SP, Clarke SW. Therapeutic aerosols 1-physical and practical considerations. Thorax 1983;38(12):881-6 A good paper on important parameters to consider for aerosol particle delivery to the lung.
15. Mitchell JP, Nagel MW, Nichols S, et al. Laser diffractometry as a technique for the rapid assessment of aerosol particle size from inhalers. J Aerosol Med 2006;19(4):409-33 . A very good review on laser diffractometry as a method for particle size analysis. (Pubitemid 46067762)
16. Dolovich M. Measurement of particle size characteristics of metered dose inhaler (MDI) aerosols. J Aerosol Med 1991;4(3):251-63
17. Mitchell JP, Nagel MW. Cascade impactors for the size characterization of aerosols from medical inhalers: Their uses and limitations. J Aerosol Med 2003;16(4):341-77 A good review on the application of cascade impactors for particle size analysis.
18. Heyder J, Gebhart J, Rudolf G, et al. Deposition of particles in the human respiratory tract in the size range 0.005-15. Am J Aerosol Sci 1986;17:811-25 (Pubitemid 17492310)
19. Dunbar C, Mitchell J. Analysis of cascade impactor mass distributions. J Aerosol Med 2005;18(4):439-51 (Pubitemid 43038409)
20. Stein SW. Aiming for a moving target: Challenges with impactor measurements of MDI aerosols. Int J Pharm 2008;355(1-2):53-61
21. Rao N, Kadrichu N, Ament B. Application of a droplet evaporation model to aerodynamic size measurement of drug aerosols generated by a vibrating mesh nebulizer. J Aerosol Med Pulm Drug Deliv 2010. [Epub ahead of print]
22. Bonam M, Christopher D, Cipolla D, et al. Minimizing variability of cascade impaction measurements in inhalers and nebulizers. AAPS PharmSciTech 2008;9(2):404-13 . An important paper on how to minimize variability when using cascade impactors.
23. Marple VA, Roberts DL, Romay FJ, et al. Next generation pharmaceutical impactor (a new impactor for pharmaceutical inhaler testing). Part I: Design. J Aerosol Med 2003;16:283-99 . An important paper on strategies to improve cascade impactors.
24. Andersen AA. New sampler for the collection, sizing, and enumeration of viable airborne particles. J Bacteriol 1958;76:471-84 . The pioneering work on Andersen cascade impactors for particle size analysis.
25. Guo C, Gillespie SR, Kauffman J, et al. Comparison of delivery characteristics from a combination metered-dose inhaler using the Andersen cascade impactor and the next generation pharmaceutical impactor. J Pharm Sci 2008;97(8):3321-34
26. Mitchell JP, Nagel MW, Avvakoumova V, et al. The abbreviated impactor measurement (AIM) concept: Part II-Influence of evaporation of a volatile component-evaluation with a 'droplet-producing' pressurized metered dose inhaler (pMDI)-based formulation containing ethanol as cosolvent. AAPS PharmSciTech 2009;10(1):252-7 A good paper on ways to shorten the steps involved when analyzing particles with cascade impactors.
27. Mitchell JP, Nagel MW, Avvakoumova V, et al. The abbreviated impactor measurement (AIM) concept: Part 1-Influence of particle bounce and re-entrainment-evaluation with a 'dry' pressurized metered dose inhaler (pMDI)-based formulation. AAPS PharmSciTech 2009;10(1):243-51
28. Swithenbank J, Beer JM, Taylor DS. A laser diagnostic technique for the measurement of droplet and particle size distribution. Prog Astronaut Aeronaut 1977;53:421-47
29. Mitchell JP, Tservistas M. Laser diffractometry and cascade impaction for nebulizer product characterization. Pharmeur Sci Notes 2006;2006(2):49-52
30. Mitchell JP, Nagel MW. Particle size analysis of aerosols from medicinal inhalers. Kona 2004;22:32-65
31. Tsagogiorgas C, Krebs J, Pukelsheim M, et al. Semifluorinated alkanes-a new class of excipients suitable for pulmonary drug delivery. Eur J Pharm Biopharm 2010;76(1):75-82
32. Xu Z, Mansour HM, Mulder T, et al. Dry powder aerosols generated by standardized entrainment tubes from drug blends with lactose monohydrate: 1. Albuterol sulfate and disodium cromoglycate. J Pharm Sci 2010;99(8):3398-414
33. Wong W, Fletcher DF, Traini D, et al. Particle aerosolization and break-up in dry powder inhalers 1: Evaluation and modelling of venturi effects for agglomerated systems. Pharm Res 2010;27(7):1367-76
34. Ehtezazi T, Saleem I, Shrubb I, et al. The interaction between the oropharyngeal geometry and aerosols via pressurised metered dose inhalers. Pharm Res 2010;27(1):175-86
35. Clark A, Borgstrom L. In vitro testing of pharmaceutical aerosols and predicting lung deposition from in vitro measurements. In: Bisgaard H, O' Callaghan C, Smaldone GC, editors, Drug delivery to the lung. Marcel Dekker, New York, USA; 2002. p. 105-42
36. Dennis JH, Pieron CA. Quality control and standards in nebulizer performance and use. In: Boe J, O'Driscoll R, Dennis JH, editors, Practical handbook of nebulizer therapy. Martin Dunitz, London, USA; 2004. p. 19-40
37. Kuhli M, Weiss M, Steckel H. A sampling and dilution system for droplet aerosols from medical nebulisers, developed for use with an optical particle counter. J Aerosol Sci 2009;40:523-33
38. Kuhli M, Weiss M, Steckel H. A new approach to characterise pharmaceutical aerosols: Measurement of aerosol from a single dose aqueous inhaler with an optical particle counter. Eur J Pharm Sci 2010;39(1-3):45-52 This paper describes particle size analysis using an optical particle counter.
39. Kuhli M, Weiss M, Steckel H. Characterisation of solution-based pressurised metered-dose inhaler aerosols with an optical particle counter. Eur J Pharm Biopharm 2010;75(3):393-8
40. Davies NM, Feddah MR. A novel method for assessing dissolution of aerosol inhaler products. Int J Pharm 2003;255(1-2):175-87
41. Dolovich MB, Jordana M, Newhouse MT. Methodologic considerations in mucociliary clearance and lung epithelial absorption measurements. Eur J Nucl Med 1987;13:S45-52 (Pubitemid 17111830)
42. Salama RO, Traini D, Chan HK, et al. Preparation and characterisation of controlled release co-spray dried drug-polymer microparticles for inhalation 2: Evaluation of in vitro release profiling methodologies for controlled release respiratory aerosols. Eur J Pharm Biopharm 2008;70(1):145-52
43. McConville JT. Development of standardized dissolution test method for inhaled pharmaceutical formulations. Int J Pharm 2009;382(1-2):15-22 . This paper describes a standardized dissolution test for inhaled formulations.
44. Mezzena M, Scalia S, Young PM, et al. Solid lipid budesonide microparticles for controlled release inhalation therapy. AAPS J 2009;11(4):771-8
45. Onoue S, Sato H, Kawabata Y, et al. In vitro and in vivo characterization on amorphous solid dispersion of cyclosporine A for inhalation therapy. J Control Release 2009;138(1):16-23
46. United States Pharmacopeia and National Formulary, United States Pharmacopia Convention, Inc., Rockville, MD, USA, 26th edition., 2003
47. Beyssac E, Lavigne J. Dissolution study of active pharmaceutical ingredients using the flow through Apparatus USP 4. Dissolution Tech 2005;12(2):23-5 . This paper describes a dissolution test using flow-through Apparatus USP 4, a method that was later modified for dissolution studies of inhaled aerosols.
48. Franz TJ. Percutaneous absorption on the relevance of in vitro data. J Invest Dermatol 1975;64(3):190-5
49. Ungaro F, De Rosa G, Miro A, et al. Cyclodextrins in the production of large porous particles: Development of dry powders for the sustained release of insulin to the lungs. Eur J Pharm Sci 2006;28:423-32 (Pubitemid 44038350)
50. Kwon MJ, Bae JH, Kim JJ, et al. Long acting porous microparticle for pulmonary protein delivery. Int J Pharm 2007;333:5-9
51. McConville JT, Patel N, Ditchburn N, et al. Use of a novel modified TSI for the evaluation of controlled-release aerosol formulations I. Drug Dev Ind Pharm 2000;26:1191-8
52. Ansoborlo E, Guilmette RA, Hoover MD, et al. Application of in vitro dissolution tests to different uranium compounds and comparison with in vivo data. Radiat Protect Dosim 1998;79:33-7 (Pubitemid 28466894)
53. Sdraulig S, Franich R, Tinker RA, et al. In vitro dissolution studies of uranium bearing material in simulated lung fluid. J Env Radioactivity 2008;99:527-38 (Pubitemid 351312832)
54. Arora P, Sharma S, Garg S. Permeability issues in nasal drug delivery. Drug Discov Today 2002;7:967-75 (Pubitemid 35286901)
55. Arora D, Shah KA, Halquist MS, et al. In vitro aqueous fluid-capacity-limited dissolution testing of respirable aerosol drug particles generated from inhaler products. Pharm Res 2010;27(5):786-95 . A very good paper on physiologically relevant dissolution testing methods for inhaled drugs.
56. Davies NM, Feddah MR. A novel method for assessing dissolution of aerosol inhaler products. Int J Pharm 2003;255(1-2):175-87 . One of the first papers on in vitro dissolution studies for inhaled drugs.
57. Grainger CI, Greenwell LL, Martin GP, et al. The permeability of large molecular weight solutes following particle delivery to air-interfaced cells that model the respiratory mucosa. Eur J Pharm Biopharm 2009;71(2):318-24
58. Madlova M, Bosquillon C, Asker D, et al. In-vitro respiratory drug absorption models possess nominal functional P-glycoprotein activity. J Pharm Pharmacol 2009;61(3):293-301
59. Forbes B, Ehrhardt C. Human respiratory epithelial cell culture for drug delivery applications. Eur J Pharm Biopharm 2005;60(2):193-205 (Pubitemid 40804561)
60. Castell JV, Donato MT, Gomez-Lechon MJ. Metabolism and bioactivation of toxicants in the lung. The in vitro cellular approach. Exp Toxicol Pathol 2005;57(Suppl 1):189-204
61. Braun A, Hammerle S, Suda K, et al. Cell cultures as tools in biopharmacy. Eur J Pharm Sci 2000;11(Suppl 2):S51-60
62. Berube K, Prytherch Z, Job C, et al. Human primary bronchial lung cell constructs: The new respiratory models. Toxicology 2010. [Epub ahead of print]
63. Sporty JL, Horalkova L, Ehrhardt C. In vitro cell culture models for the assessment of pulmonary drug disposition. Expert Opin Drug Metab Toxicol 2008;4(4):333-45 A good review on cell culture models for pulmonary drug delivery studies. (Pubitemid 351728510)
64. Sakagami M. In vivo, in vitro and ex vivo models to assess pulmonary absorption and disposition of inhaled therapeutics for systemic delivery. Adv Drug Deliv Rev 2006;58(9-10):1030-60 (Pubitemid 44712023)
65. Fiegel J, Ehrhardt C, Schaefer UF, et al. Large porous particle impingement on lung epithelial cell monolayers-toward improved particle characterization in the lung. Pharm Res 2003;20(5):788-96 . An interesting paper that describes particle impingement on cultured cells. (Pubitemid 36515312)
66. de Jong PM, van Sterkenburg MA, Kempenaar JA, et al. Serial culturing of human bronchial epithelial cells derived from biopsies. In Vitro Cell Dev Biol Anim 1993;29A(5):379-87
67. Forbes B, Lim S, Martin GP, et al. An in vitro technique for evaluating inhaled nasal delivery systems. STP Pharma 2002;12:75-9 . An interesting paper on the evaluation of inhaled nasal drugs that was later adapted for dissolution studies for respiratory drugs. (Pubitemid 34093352)
68. Cooney D, Kazantseva M, Hickey AJ. Development of a size-dependent aerosol deposition model utilising human airway epithelial cells for evaluating aerosol drug delivery. Altern Lab Anim 2004;32(6):581-90 (Pubitemid 40321537)
69. Bur M, Rothen-Rutishauser B, Huwer H, et al. A novel cell compatible impingement system to study in vitro drug absorption from dry powder aerosol formulations. Eur J Pharm Biopharm 2009;72(2):350-7 . A new impingement method for aerosol deposition to cultured cells.
70. Bur M, Huwer H, Muys L, et al. Drug transport across pulmonary epithelial cell monolayers: Effects of particle size, apical liquid volume, and deposition technique. J Aerosol Med Pulm Drug Deliv 2010;23(3):119-27 This paper describes some important variables that can affect in vitro drug delivery studies involving tissue culture methods.
71. Wiedmann TS, Bhatia R, Wattenberg LW. Drug solubilization in lung surfactant. J Control Release 2000;65(1-2):43-7 (Pubitemid 30122913)
72. Sinswat P, Overhoff KA, McConville JT, et al. Nebulization of nanoparticulate amorphous or crystalline tacrolimus-single-dose pharmacokinetics study in mice. Eur J Pharm Biopharm 2008;69(3):105710-66
73. Pavy-Le Traon A, Saivin S, Soulez-LaRiviere C, et al. Pharmacology in space: Pharmacotherapy. Adv Space Biol Med 1997;6:93-105
74. dos Santos MA, Bosquillona C, Russomano T, et al. Modelling the effects of microgravity on the permeability of air interface respiratory epithelial cell layers. Adv Space Res 2010;46(6):712-18
75. Jaafar-Maalej C, Andrieu V, Elaissari A, Fessi H. Assessment methods of inhaled aerosols: Technical aspects and applications. Expert Opin Drug Deliv 2009;6(9):941-59
76. Fernandes CA, Vanbever R. Preclinical models for pulmonary drug delivery. Expert Opin Drug Deliv 2009;6(11):1231-45
77. Schanker LS. Drug absorption from the lung. Biochem Pharmacol 1978;27:381-5
78. Chilvers MA, O'Callaghan C. Local mucociliary defence mechanisms. Paediatr Respir Rev 2000;1(1):27-34
79. Ross HH, Romrell LJ, Kaye GI. Respiratory system, histology -A text and atlas; Williams & Wilkins, Baltimore; 1995. p. 530-57
80. Saumon G, Soler P, Martet G. Effect of polycations on barrier and transport properties of alveolar epithelium in situ. Am J Physiol 1995;269(2 Pt 1):L185-94
81. Niemeier RW. The isolated perfused lung. Environ Health Perspect 1984;56:35-41 . This paper describes the importance of isolated perfused lung method.
82. Valle MJ, Gonzalez LF, Sanchez NA. Pulmonary versus systemic delivery of levofloxacin. The isolated lung of the rat as experimental approach for assessing pulmonary inhalation. Pulm Pharmacol Ther 2008;21(2):298-303
83. Saumon G, Soler P, Martet G. Effect of polycations on barrier and transport properties of alveolar epithelium in situ. Am J Physiol 1995;269(2 Pt 1):L185-94
84. Eljamal M, Nagarajan S, Patton JS. In situ and in vivo methods for pulmonary delivery. Pharm Biotechnol 1996;8:361-74
85. Newman SP, Chan HK. In vitro/in vivo comparisons in pulmonary drug delivery. J Aerosol Med Pulm Drug Deliv 2008;21(1):77-84 . An interesting paper on in vitro/ in vivo correlations.
86. Newman SP, Wilding IR, Hirst PH. Human lung deposition data: The bridge between in vitro and clinical evaluations for inhaled drug products? Int J Pharm 2000;208(1-2):49-60
87. Bur M, Henning A, Hein S, et al. Inhalative nanomedicine-opportunities and challenges. Inhal Toxicol 2009;21(Suppl 1):137-43
88. Jaafar-Maalej C, Andrieu V, Elaissari A, et al. Assessment methods of inhaled aerosols: Technical aspects and applications. Expert Opin Drug Deliv 2009;6(9):941-59
89. Kim CS. Methods of calculating lung delivery and deposition of aerosol particles. Respir Care 2000;45(6):695-711
90. Cryan SA, Sivadas N, Garcia-Contreras L. In vivo animal models for drug delivery across the lung mucosal barrier. Adv Drug Deliv Rev 2007;59(11):1133-51 (Pubitemid 47628783)
91. Fleming JS, Hashish AH, Conway JH, et al. Assessment of deposition of inhaled aerosol in the respiratory tract of man using three-dimensional multimodality imaging and mathematical modeling. J Aerosol Med 1996;9(3):317-27
92. Schroeter J, Fleming J, Hwang D, et al. A computer model of lung morphology to analyze SPECT images. Comput Med Imaging Graph 2002;26(4):237-46 (Pubitemid 34628867)
93. Hindle M, Chrystyn H. Determination of the relative bioavailability of salbutamol to the lung following inhalation. Br J Clin Pharmacol 1992;34(4):311-15
94. Lee SL, Adams WP, Li BV, et al. In vitro considerations to support bioequivalence of locally acting drugs in dry powder inhalers for lung diseases. AAPS J 2009;11(3):414-23
95. Tomlinson HS, Corlett SA, Chrystyn H. Effect of dose on the relative lung bioavailability of salbutamol. J Aerosol Med 1995;8:P193
96. Silkstone VL, Corlett SA, Chrystyn H. Relative lung and total systemic bioavailability following inhalation from a metered dose inhaler compared with a metered dose inhaler attached to a large volume plastic spacer and a jet nebulizer. Eur J Clin Pharmacol 2002;57(11):781-6 (Pubitemid 34143335)
97. Chrystyn H, Allen MB, Corlett SA. Simultaneous measurement of pharmacodynamic and pharmacokinetic parameters which can be used to evaluate the equivalence of inhaled salbutamol. Am Rev Respir Crit Care Med 1998;157:A636
98. Lipworth B. Pharmacokinectics of inhaled drugs. Br J Clin Pharmacol 1996;42(6):697-705
99. Finlay WH, Martin AR. Recent advances in predictive understanding of respiratory tract deposition. J Aerosol Med Pulm Drug Deliv 2008;21(2):189-206
100. de Matas M, Shao Q, Silkstone VL, et al. Evaluation of an in vitro in vivo correlation for nebulizer delivery using artificial neural networks. J Pharm Sci 2007;96(12):3293-303 (Pubitemid 350235194)
101. Kunka R, Andrews S, Pimazzoni M, et al. From hydrofluoroalkane pressurized metered dose inhalers (pMDIs) and comparability with chlorofluorocarbon pMDIs. Respir Med 2000;94(Suppl B):S10-16
102. Silkstone VL, Dennis JH, Pieron CA, et al. An investigation of in vitro/in vivo correlations for salbutamol nebulized by eight systems. J Aerosol Med 2002;15(3):251-9
103. Srichana T, Suedee R, Muanpanarai D, et al. The study of in vitro-in vivo correlation: Pharmacokinetics and pharmacodynamics of salbutamol dry powder inhalers. J Pharm Sci 2005;94(1):220-30 (Pubitemid 40116385)
104. de Matas M, Shao Q, Richardson CH, et al. Evaluation of in vitro in vivo correlations for dry powder inhaler delivery using artificial neural networks. Eur J Pharm Sci 2008;33(1):80-90 . This paper describes a strategy for estimating in vitro/in vivo correlations using artificial neural networks. (Pubitemid 350235194)
105. Warheit DB, Sayes CM, Reed KL. Nanoscale and fine zinc oxideparticles: Can in vitro assays accurately forecast lung hazardsfollowing inhalation exposures? Environ Sci Technol 2009;43(20):7939-45