Advertisement

AAPS PharmSciTech

, 12:965 | Cite as

Non-impactor-Based Methods for Sizing of Aerosols Emitted from Orally Inhaled and Nasal Drug Products (OINDPs)

  • Jolyon Mitchell
  • Richard Bauer
  • Svetlana Lyapustina
  • Terrence Tougas
  • Volker Glaab
Review Article

Abstract

The purpose of this article is to review non-impactor-based methods for measuring particle size distributions of orally inhaled and nasal pharmaceutical aerosols. The assessment of the size distributions of sprays and aerosols from orally inhaled and nasal drug products by methods not involving multi-stage cascade impaction may offer significant potential advantages in terms of labor savings and reducing the risk for operator-related errors associated with complex-to-undertake impactor-based methods. Indeed, in the case of nasal spray products, cascade impaction is inappropriate and alternative, and preferably non-invasive methods must be sought that minimize size-related bias associated with the measurement process for these relatively large droplets. This review highlights the options that are available to those involved with product quality assessments, providing guidance on relative strengths and weaknesses, as well as highlighting precautions that should be observed to minimize bias. The advent of Raman chemical imaging, which enables an estimate to be made of the proportion of each particle comprising active pharmaceutical ingredient(s) (APIs), necessitates a re-think about the value of classical microscopy image analysis as now being capable of providing API-relevant information from collected aerosols and sprays.

Key words

aerosol efficient data analysis measurement techniques size distribution spray 

Notes

ACKNOWLEDGEMENTS

The authors are grateful for the technical advice received from colleagues within the IPAC-RS Cascade Impactor Working Group, as well as recommendations from the IPAC-RS Board of Directors during the internal review process. They also wish to acknowledge helpful scientific discussions with Dr. Julie Suman (NextBreath, LLC) and Mr. William Doub (U.S. FDA, CDER) regarding application of RCI to the study of nasal spray-based formulations.

REFERENCES

  1. 1.
    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. doi: 10.1089/089426803772455622.PubMedCrossRefGoogle Scholar
  2. 2.
    Christopher D, Curry P, Doub W, Furnkranz K, Lavery M, Lin K, et al. Considerations for the development and practice of cascade impaction testing including a mass balance failure investigation tree. J Aerosol Med. 2003;16(3):235–47. doi: 10.1089/089426803769017604.PubMedCrossRefGoogle Scholar
  3. 3.
    Bonam M, Christopher D, Cipolla D, Donovan B, Goodwin D, Holmes S, et al. Minimizing variability of cascade impaction measurements in inhalers and nebulizers. AAPS PharmSciTechnol. 2008;9(2):404–13. doi: 10.1208/s12249-008-9045-9.CrossRefGoogle Scholar
  4. 4.
    US Food Drug Administration. Guidance for Industry: Quality Systems Approach to Pharmaceutical CGMP Regulations. September 2006. Available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070337.pdf. Accessed 2 Nov 2010.
  5. 5.
    Suman JD, Laube BL, Dalby R. Comparison of nasal deposition and clearance of aerosol generated by a nebulizer and an aqueous spray pump. Pharm Res. 1999;16:1648–52.PubMedCrossRefGoogle Scholar
  6. 6.
    Marple VA, Rubow KL, Olson BA. Inertial, gravitational, centrifugal, and thermal collection techniques. In: Baron PA, Willeke K, editors. Aerosol measurement: principles, techniques and applications. 2nd ed. New York: Wiley Interscience; 2001. p. 229–60.Google Scholar
  7. 7.
    Suman JD, Laube BL, Lin T, Brouet G, Dalby R. Relevance of in vitro tests of nasal solutions to predict in vivo deposition. Pharm Res. 2002;19:1–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Mitchell JP, Nagel M. Particle size analysis of aerosols from medicinal inhalers. KONA-Powder and Particle. 2004;22:32–65.Google Scholar
  9. 9.
    Hinds WC. Properties, behavior, and measurement of airborne particles. 2nd ed. New York: Wiley-Interscience; 1999.Google Scholar
  10. 10.
    Heyder J, Svartengren MU. Basic principles of particle behavior in the human respiratory tract. In: Bisgaard H, O’Callaghan C, Smaldone GC, editors. Drug delivery to the lung. New York: Marcel Dekker; 2002. p. 21–45.Google Scholar
  11. 11.
    Adjei AL, Qiu Y, Gupta PK. Bioavailability and pharmacokinetics of inhaled drugs. In: Hickey AJ, editor. Inhalation aerosols: physical and biological basis for therapy. New York: Informa Healthcare; 2007. p. 187–218.Google Scholar
  12. 12.
    FDA-CDER. Draft guidance: metered dose inhaler (MDI) and dry powder inhaler (DPI) drug products chemistry, manufacturing and controls documentation. 1998. Docket 98D-0997. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070573.pdf. Accessed 4 Mar 2011
  13. 13.
    FDA-CDER. Nasal spray and inhalation solution, suspension, and spray drug products chemistry, manufacturing, and controls documentation. 2002. Docket No. 99D-1454. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070575.pdf. Accessed 4 Mar 2011.
  14. 14.
    Fuhrman M, Priore R, Oksana K, Oksana O. Automation of ingredient-specific particle sizing using Raman Chemical Imaging. U.S. Patent Office, January 8, 2010. Patent Application 12/684495.Google Scholar
  15. 15.
    Mansour HM, Hickey AJ. Raman characterization and chemical imaging of biocolloidal self-assemblies, drug delivery systems, and pulmonary inhalation aerosols: a review. AAPS PharmSciTechnol. 2007;8(4):Article 99. http://www.aapspharmscitech.org/view.asp?art=pt0804099. Accessed 4 Mar 2011.
  16. 16.
    Baron PA, Mazumder MK, Cheng YS. Direct-reading techniques using optical particle detection. In: Willeke K, Baron PA, editors. Aerosol measurement: principles, techniques and applications. New York: Van Nostrand Reinhold; 1993. p. 381–409.Google Scholar
  17. 17.
    Mitchell JP, Nagel MW. Time-of-flight aerodynamic particle size analyzers: their use and limitations for the evaluation of medical aerosols. J Aerosol Med. 1999;12(4):217–40. doi: 10.1089/jam.1999.12.217.PubMedCrossRefGoogle Scholar
  18. 18.
    Chen BT, Cheng YS, Yeh HC. Performance of a TSI aerodynamic particle sizer. Aerosol Sci Technol. 1985;4:89–97.CrossRefGoogle Scholar
  19. 19.
    Harris J, Stein SW, Myrdal PB. Evaluation of the TSI Aerosol Impactor 3306/3321 system using a redesigned impactor stage with solution and suspension metered-dose inhalers. AAPS PharmSciTechnol. 2006; 7(1): Article 20. doi: 10.1208/pt070120.
  20. 20.
    Tiwari D, Goldman G, Malick WA, Madan PL. Formulation and evaluation of albuterol metered dose inhalers containing tetrafluoroethane (P134a), a non-CFC propellant. Pharm Dev Technol. 1998;3(2):163–74.PubMedCrossRefGoogle Scholar
  21. 21.
    Bouchikhi A, Becquemin MH, Bignon, Roy JM, Teillac A. Particle size study of nine metered dose inhalers, and their deposition probabilities in the airways. Eur Resp J. 1988;1:547–52.Google Scholar
  22. 22.
    Mitchell JP, Nagel MW, Wiersema KJ, Doyle CC. Aerodynamic particle size analysis of aerosols from pressurized metered-dose inhalers: comparison of Andersen 8-stage cascade impactor, Next Generation Pharmaceutical Impactor, and model 3321 aerodynamic particle sizer aerosol spectrometer. AAPS PharmSciTechnol. 2003;4:Article 54.Google Scholar
  23. 23.
    Stein SW, Myrdal PB. A theoretical and experimental analysis of formulation and device parameters affecting solution MDI size distributions. J Pharm Sci. 2004;93:2158–75.PubMedCrossRefGoogle Scholar
  24. 24.
    Terzano C, Mannino F. Aerosol characterization of three corticosteroid MDIs with Volumatic™ holding chamber and MDIs alone at two inspiratory flow rates. J Aerosol Med. 1999;12(4):249–54. doi: 10.1089/jam.1999.12.249.PubMedCrossRefGoogle Scholar
  25. 25.
    Myrdal PB, Stein SW, Mogalian E, et al. Comparison of the TSI Model 3306 Impactor Inlet with the Andersen cascade impactor: solution metered dose inhalers. Drug Dev Ind Pharm. 2004;30:859–68.PubMedCrossRefGoogle Scholar
  26. 26.
    Mogalian E, Myrdal PB. Application of USP inlet extensions to the TSI Impactor System 3306/3320 using HFA 227 based metered dose inhalers. Drug Dev Ind Pharm. 2005;31:977–85.PubMedCrossRefGoogle Scholar
  27. 27.
    Myrdal PB, Mogalian E, Mitchell JP, Nagel M, Wright C, Kiser B, et al. Application of heated inlet extensions to the TSI 3306/3321 system: comparison with the Andersen cascade impactor and next generation impactor. J Aerosol Med. 2006;19(4):543–54. doi: 10.1089/jam.2006.19.543.PubMedCrossRefGoogle Scholar
  28. 28.
    Cheng YS, Yazzie D, Gao J, Muggli D, Etter J, Rosenthanl GJ. Particle characteristics and lung deposition patterns in a human airway replica of a dry powder formulation of polylactic acid produced using supercritical fluid technology. J Aerosol Med. 2003;16(1):65–73. doi: 10.1089/089426803764928374.PubMedCrossRefGoogle Scholar
  29. 29.
    Kuehl PJ, Barrett EG, McDonald JD, Rudolph K, Vodak D, Dobry D, et al. Formulation development and in vivo evaluation of a new dry powder formulation of albuterol sulphate in beagle dogs. Pharm Res. 2010;27:894–904. doi: 10.1007/s11095-010-0084-z.PubMedCrossRefGoogle Scholar
  30. 30.
    Marshall IA, Mitchell JP, Griffiths WD. The behavior of regular-shaped, non-spherical particles in a TSI aerodynamic particle sizer. J Aerosol Sci. 1991;22(1):73–89.CrossRefGoogle Scholar
  31. 31.
    Cheng Y-S, Chen BT, Yeh HC, Marshall IA, Mitchell JP, Griffiths WD. Behavior of compact non-spherical particles in the TSI aerodynamic particle sizer model APS33B: ultra-Stokesian drag forces. Aerosol Sci Technol. 1993;19(3):255–67.CrossRefGoogle Scholar
  32. 32.
    Griffiths WD, Iles PJ, Vaughan NP. The behavior of liquid droplets in an APS3300. J Aerosol Sci. 1986;17(6):921–30.CrossRefGoogle Scholar
  33. 33.
    Cheng Y-S, Chen BT, Yeh HC. A study of density effect and droplet deformation in the TSI aerodynamic particle sizer. Aerosol Sci Technol. 1990;12:278–85. http://www.informaworld.com/smpp/ftinterface∼content=a778641175∼fulltext=713240930∼frm=content. Accessed 9 Feb 2011
  34. 34.
    Ho J Y-W. Fluorescent biological particle detection system. US Patent 5701012. 1997.Google Scholar
  35. 35.
    Baron PA, Mazumder MK, Cheng Y-S. Direct-reading techniques using particle motion and optical detection. In: Baron PA, Willeke K, editors. Aerosol measurement: principles, techniques, and applications. New York: Wiley; 2001. p. 495–535.Google Scholar
  36. 36.
    Ali M. A novel method of characterizing medicinal drug aerosols generated from pulmonary drug delivery devices. PDA J Pharm Sci Technol. 2010;64(4):364–72.PubMedGoogle Scholar
  37. 37.
    Philip VA, Mehta RC, Mazumder MK, DeLuca PP. Effect of surface treatment on the respirable fractions of PLGA microspheres formulated for dry powder inhalers. Int J Pharm. 1997;151(2):165–74.CrossRefGoogle Scholar
  38. 38.
    Saini D, Biris AS, Srirama PK, Mazumder MK. Particle size and charge distribution analysis of pharmaceutical aerosols generated by inhalers. Pharm Dev Technol. 2007;12(1):35–41.PubMedCrossRefGoogle Scholar
  39. 39.
    Philip VA, Mehta RC, DeLuca PP, Mazumder MK. E-SPART analysis of poly(D, L-lactide-co-glycolide) microspheres formulated for dry powder aerosols. Particulate Sci Technol. 1997;15:303–16.CrossRefGoogle Scholar
  40. 40.
    Ali M, Sharma R, Srirama PK, Mazumder MK. In-vitro studies of nebulizer aerosol particles deposition as a function of aerodynamic size and electrostatic charge in an anatomical throat cast. Presentation at the Frontiers in Aerosol Dosimetry Research Conference, Beckman Center of the National Academies, Irvine, California, USA, October 24–25, 2005.Google Scholar
  41. 41.
    International Standards Organization, Geneva, Switzerland, Particle size analysis—laser diffraction methods. ISO 13320; 2009.Google Scholar
  42. 42.
    Mitchell JP, Nagel MW, Nichols SC, Nerbrink O. Laser diffractometry as a technique for the rapid assessment of aerosol particle size from inhalers. J Aerosol Med. 2006;19(4):409–33. doi: 10.1089/jam.2006.19.409.PubMedCrossRefGoogle Scholar
  43. 43.
    Krarup HG, Bumiller M, Stauffer T. The Malvern Spraytec applied to pharmaceutical spray analysis. In: Dalby RN, Byron PR, Peart J, Farr SJ, editors. Respiratory drug delivery VIII. Raleigh: Davis Horwood International; 2002. p. 505–8.Google Scholar
  44. 44.
    Kwong WTJ, Ho SL, Coates AL. Comparison of nebulized particle size distribution with Malvern laser diffraction analyzer versus Andersen cascade impactor and low-flow Marple personal cascade impactor. J Aerosol Med. 2000;13(4):303–14. doi: 10.1089/jam.2000.13.303.PubMedCrossRefGoogle Scholar
  45. 45.
    Vecellio None L, Grimbert D, Becquemin MH, Boissinot E, LePape A, Lemarié E, et al. Validation of a laser diffraction method as a substitute for cascade impaction in the European project for a nebulizer standard. J Aerosol Med. 2001;14(1):107–14. doi: 10.1089/08942680152007954.PubMedCrossRefGoogle Scholar
  46. 46.
    Clark AR. The use of laser diffraction for the evaluation of the aerosol clouds generated by medical nebulizers. Int J Pharm. 1995;115:69–78.CrossRefGoogle Scholar
  47. 47.
    US Food and Drug Administration. 1993. CDRH reviewer guidance for nebulizers, metered dose inhalers, spacers and actuators. Rockville: FDA. http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm081282.htm. Accessed 4 Mar 2011.
  48. 48.
    European Medicines Agency (EMEA). Guideline on the pharmaceutical quality of inhalation and nasal products. 2006; EMEA/CHMP/QWP/49313/2005 Final. London, UK. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003568.pdf. Accessed 4 Mar 2011.
  49. 49.
    US Food and Drug Administration. CDER draft guidance for industry: bioavailability and bioequivalence studies for nasal aerosols and nasal sprays for local action. Rockville: FDA. 2003. http://www.fda.gov/ohrms/dockets/ac/00/backgrd/3609b1l.pdf. Accessed 4 Mar 2011.
  50. 50.
    Smart J, Berg E, Nerbrink O, Zuban R, Blakey D, New M. Touchspray™ technology: a comparison of the droplet size measured by cascade impaction and laser diffraction. In: Dalby RN, Byron PR, Peart J, Farr SJ, editors. Respiratory drug delivery VIII. Raleigh: Davis Horwood International; 2002. p. 525–7.Google Scholar
  51. 51.
    Moslemi P, Najafabadi AR, Tajerzadeh H. Evaluations of different parameters that affect droplet size distribution of nasal gel sprays. In: Dalby RN, Byron PR, Peart J, Farr SJ, editors. Respiratory drug delivery VIII. Raleigh: Davis Horwood International; 2002. p. 619–22.Google Scholar
  52. 52.
    De Boer AH, Gjaltema G, Witt W, Frijlink HW. The use of laser diffraction technique for the characterization of the aerosol cloud from inhalation devices. In: Dalby RN, Byron PR, Farr SJ, Peart J, editors. Respiratory drug delivery VII. Raleigh: Serentec; 2000. p. 585–7.Google Scholar
  53. 53.
    Zeng X-M, MacRitchie HB, Marriott C, Martin GP. Correlation between inertial impaction and laser diffraction sizing data for aerosolized carrier-based dry powder formulations. Pharm Res. 2006;23(9):2200–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Stevens S, Shrimpton J, Palmer M, Prime D, Johal B. Accuracy assessments for laser diffraction measurements of pharmaceutical lactose. Meas Sci Technol. 2007;18:3697–706.CrossRefGoogle Scholar
  55. 55.
    Etzler FM, Deanne R. Particle size analysis: a comparison of various methods. Part Part Syst Char. 1997;14:278–82.CrossRefGoogle Scholar
  56. 56.
    Gebhart J. Optical-direct reading techniques: light intensity systems. In: Baron PA, Willeke K, editors. Aerosol measurement: principles, techniques, and applications. New York: Wiley; 2001. p. 313–44.Google Scholar
  57. 57.
    Mitchell J, Ashcroft J, Fromentin A, Holmes R, Marsault P, McAughey JJ, et al. Laboratory intercomparison of Polytec optical aerosol analyzers. In: Masuda S, Takahashi K, editors. Proc. 3rd Int. Aerosol Conf. Kyoto, Japan. Oxford: Pergamon; 1990. p. 643–6.Google Scholar
  58. 58.
    Umhauer H. Particle size distribution analysis by scattered light measurements using an optically defined measuring volume. J Aerosol Sci. 1983;14:765–70.CrossRefGoogle Scholar
  59. 59.
    Jaenicke R. The optical particle counter: cross-sensitivity and coincidence. J Aerosol Sci. 1972;3(2):95–111.CrossRefGoogle Scholar
  60. 60.
    Rader DJ, O’Hern TJ. Optical direct-reading techniques: in situ sensing. In: Willeke K, Baron PA, editors. Aerosol measurement: principles, techniques and applications. New York: Van Nostrand Reinhold; 1993. p. 345–80.Google Scholar
  61. 61.
    Mitchell JP, Nichols AL, Van Santen A. The characterisation of water-droplet aerosols by polytec optical particle analysers. Part Part Syst Charact. 1989;6:119–23. doi: 10.1002/ppsc.19890060120.CrossRefGoogle Scholar
  62. 62.
    Loffert DT, Ikle D, Nelson HS. A comparison of commercial jet nebulizers. Chest. 1994;106:1788–92.PubMedCrossRefGoogle Scholar
  63. 63.
    Jaeger R, Schmidt M, Weiss M. Inhalation aerosol spectrometry (INAS®) for the real-time evaluation of particle size distribution and inhaled drug concentration in therapeutic and toxicologic research. In: Dalby RN, Byron PR, Peart J, Suman JD, Farr SJ, Young PM, editors. Respiratory drug delivery—2010. River Grove: Davis Healthcare Int.; 2010. p. 489–93.Google Scholar
  64. 64.
    Farmer WM. Measurement of particle size, number density and velocity using a laser interferometer. Appl Optics. 1972;11:2603–12.CrossRefGoogle Scholar
  65. 65.
    Negus CR, Drain LE. Mie calculations of the scattered light from a spherical particle traversing a fringe system produced by two intersecting laser beams. J Phys D: Applied Physics. 1982;15:375–402.CrossRefGoogle Scholar
  66. 66.
    Bachalo WD, Hauser MJ. Phase/Doppler spray analyzer for simultaneous measurements of drop size and velocity distributions. Opt Eng. 1984;23(5):583–90.Google Scholar
  67. 67.
    Stapleton KW, Finlay WH, Zuberbuhler P. An in-vitro method for determining regional dosages delivered by jet nebulizers. J Aerosol Med. 1994;7:325–44.PubMedCrossRefGoogle Scholar
  68. 68.
    Dunbar CA, Watkins AP, Miller JF. An experimental investigation of the spray issued from a pMDI using laser diagnostic techniques. J Aerosol Med. 1997;10(4):351–68. doi: 10.1089/jam.1997.10.351.PubMedCrossRefGoogle Scholar
  69. 69.
    Kakade PP, Versteeg HK, Hargrave GK, Genova P, Williams RC, Deaton D. Design optimization of a novel pMDI actuator for systemic drug delivery. J Aerosol Med. 2007;20(4):460–74. doi: 10.1089/jam.2007.0595.PubMedCrossRefGoogle Scholar
  70. 70.
    Ranucci JA, Chen FC. Phase Doppler anemometry: a technique for determining aerosol plume-particle size and velocity. Pharm Technol. 1993;17:62. 64,68,70,72,74.Google Scholar
  71. 71.
    Corcoran TE, Hitron R, Humphrey W, Chigier N. Optical measurement of nebulizer sprays: a quantitative comparison of diffraction, phase Doppler interferometry, and time of flight techniques. J Aerosol Sci. 2000;31(1):35–50.CrossRefGoogle Scholar
  72. 72.
    US Food and Drug Administration. CDER guidance for industry: nasal spray and inhalation solution, suspension and spray drug products—chemistry, manufacturing and controls documentation. Rockville: FDA; 2002.Google Scholar
  73. 73.
    ISO 13322-1. Particle size analysis—image analysis methods—part 1: static image analysis methods. Geneva: International Standards Organization; 2004.Google Scholar
  74. 74.
    ISO 13322-2. Particle size analysis—image analysis methods—part 2: dynamic image analysis methods. Geneva: International Standards Organization; 2006.Google Scholar
  75. 75.
    McCrone WC, Delly JG. The particle atlas: volume 1, principles and techniques. Chicago: McCrone Research Institute; 1992.Google Scholar
  76. 76.
    Bradbury S. Basic measurement techniques for light microscopy, microscopy handbook 23. Oxford: Royal Microscopy Society, Oxford University Press; 1991.Google Scholar
  77. 77.
    Chambers F, Ali A, Mitchell J, Shelton C, Nichols S. Cascade impactor (CI) mensuration—an assessment of the accuracy and precision of commercially available optical measurement systems. AAPS PharmSciTechnol. 2010;11(1):472–84. doi: 10.1208/s12249-010-9405-0.CrossRefGoogle Scholar
  78. 78.
    Raula J, Lähde A, Kauppinen EI. Aerosolization behavior of carrier-free L-leucine coated salbutamol sulphate powders. Int J Pharm. 2009;365:18–25.PubMedCrossRefGoogle Scholar
  79. 79.
    Dalby RN, Tiano SL, Hickey AJ. Medical devices for the delivery of therapeutic aerosols to the lungs. In: Hickey AJ, editor. Inhalation aerosols: physical and biological basis for therapy. New York: Informa Healthcare; 2007. p. 417–44.Google Scholar
  80. 80.
    Kidder LH, Haber KS, Dubois J, Lewis EN. An analysis of agglomeration: morphologically directed Raman microscopy to characterize a dry powder inhaler. In: Dalby RN, Byron PR, Peart J, Suman JD, Farr SJ, Young PM, editors. Respiratory drug delivery—2010. River Grove: Davis Healthcare Int.; 2010. p. 633–5.Google Scholar
  81. 81.
    Shekounov BY, Chattopadhyay P, Tong HHY, Chow AHL. Particle size analysis in pharmaceutics: principles, methods and applications. Pharm Res. 2007;24(2):203–27. doi: 10.1007/s11095-006-9146-7.CrossRefGoogle Scholar
  82. 82.
    Priore RJ, Olkhovyk O, Klueva O, Fuhrman M. Automation of ingredient-specific particle sizing employing Raman chemical imaging. In: Dalby RN, Byron PR, Peart J, Suman JD, Young PM, editors. Respiratory drug delivery Europe 2009. River Grove: Davis Healthcare Int.; 2009. p. 275–8.Google Scholar
  83. 83.
    Getting to know Advair. ChemImage Pharma Focus: February Issue 2010. http://www.chemimage.com/news/newsletter/pharma_focus/feb2010.aspx. Accessed 4 Mar 2011.
  84. 84.
    Sasic S, Harding L. Global illumination Raman chemical imaging of a combination dry powder formulation. In: Dalby RN, Byron PR, Peart J, Suman JD, Farr SJ, Young PM, editors. Respiratory drug delivery—2010. River Grove: Davis Healthcare Int.; 2010. p. 729–32.Google Scholar
  85. 85.
    Valet O, Lankers M, Adi H, Traini D. Young PM. In: Dalby RN, Byron PR, Peart J, Suman JD, Farr SJ, Young PM, editors. Respiratory drug delivery—2010. River Grove: Davis Healthcare Int.; 2010. p. 763–6.Google Scholar
  86. 86.
    Priore RJ, Klueva O, Olkhovyk O, Fuhrman M. Ingredient-specific particle sizing of Combivent® metered dose inhaler. In: Dalby RN, Byron PR, Peart J, Suman JD, Farr SJ, Young PM, editors. Respiratory drug delivery—2010. River Grove: Davis Healthcare Int.; 2010. p. 499–502.Google Scholar
  87. 87.
    Doub W, Adams WP, Spencer JA, Buhse LF, Nelson MP, Treado PJ. Raman chemical imaging for ingredient-specific particle size characterization of aqueous suspension nasal spray formulations: a progress report. Pharm Res. 2007;24(5):934–45. doi: 10.1007/s11095-006-9211-2.PubMedCrossRefGoogle Scholar
  88. 88.
    US Pharmacopeia. <429> Light diffraction measurement of particle size. USP33, NF28. Rockville: US Pharmacopeial Convention; 2003.Google Scholar
  89. 89.
    US Pharmacopeia. In-process revision to Chapter <601> Aerosols, Nasal Sprays, Metered-Dose Inhalers, and Dry Powder Inhalers. Pharm.Forum. 2011;37(4). http://www.usppf.com/pf/pub/data/v374/CHA_IPR_374_c601.xml. Accessed 18 July 2011.
  90. 90.
    European Directorate for Quality in Medicines and Healthcare (EDQM). Preparations for nebulisation: characterisation, general chapter 2.9.44. Pharmeuropa. 2006;18(2):280–2.Google Scholar
  91. 91.
    United States Pharmacopeial Convention. In process revision. <1601> Products for nebulization—characterization tests. Pharm Forum. 2010;36(2):534–9.Google Scholar
  92. 92.
    United States Pharmacopeia. <776> Optical microscopy. USP33, NF28. Rockville: US Pharmacopeial Convention; 2009.Google Scholar
  93. 93.
    United States Pharmacopeia. <1181> Scanning electron microscopy. USP33, NF28. Rockville: US Pharmacopeial Convention; 2009.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2011

Authors and Affiliations

  • Jolyon Mitchell
    • 1
  • Richard Bauer
    • 2
  • Svetlana Lyapustina
    • 3
  • Terrence Tougas
    • 4
  • Volker Glaab
    • 5
  1. 1.Trudell Medical InternationalLondonCanada
  2. 2.Aerosol AnalysisMannkind CorpDanburyUSA
  3. 3.Pharmaceutical Practice GroupDrinker Biddle & Reath LLPWashington DCUSA
  4. 4.Analytical DevelopmentBoehringer IngelheimRidgefieldUSA
  5. 5.Respiratory Drug DeliveryBoehringer IngelheimIngelheim am RheinGermany

Personalised recommendations