Abstract
This review presents an introduction to Raman scattering and describes the various Raman spectroscopy, Raman microscopy, and chemical imaging techniques that have demonstrated utility in biocolloidal self-assemblies, pharmaceutical drug delivery systems, and pulmonary research applications. Recent Raman applications to pharmaceutical aerosols in the context of pulmonary inhalation aerosol delivery are discussed. The “molecular fingerprint” insight that Raman applications provide includes molecular structure, drug-carrier/excipient interactions, intramolecular and intermolecular bonding, surface structure, surface and interfacial interactions, and the functional groups involved therein. The molecular, surface, and interfacial properties that Raman characterization can provide are particularly important in respirable pharmaceutical powders, as these particles possess a higher surface-area-to-volume ratio; hence, understanding the nature of these solid surfaces can enable their manipulation and tailoring for functionality at the nanometer level for targeted pulmonary delivery and deposition. Moreover, Raman mapping of aerosols at the micro- and nanometer level of resolution is achievable with new, sophisticated, commercially available Raman microspectroscopy techniques. This noninvasive, highly versatile analytical and imaging technique exhibits vast potential for in vitro and in vivo molecular investigations of pulmonary aerosol delivery, lung deposition, and pulmonary cellular drug uptake and disposition in unfixed living pulmonary cells.
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References
Raman CV. Anisotropy of molecules.Nature. 1922;109:75–76.
Raman CV, Krishnan KS. A new type of secondary radiation.Nature. 1928;121:501–502.
Singh RCV. Raman and the discovery of the Raman effect.Phys Perspect. 2002;4:399–420.
Tudor AM, Melia CD, Binns JS, Hendra PJ, Church S, Davies MC. The application of Fourier-transform Raman spectroscopy to the analysis of pharmaceuticals and biomaterials.J Pharm Biomed Anal. 1990;8:717–720.
Newman AW, Bryn SR. Solid-state analysis of the active pharmaceutical ingredient in drug products.Drug Discov Today. 2003;8:898–905.
McCreery RL, Hom AJ, Spencer J, Jefferson E. Noninvasive identification of materials inside USP vials with Raman spectroscopy and a Raman spectral library.J Pharm Sci. 1998;87:1–8.
Lyon LA, Keating CD, Fox AP, et al. Raman spectroscopy.Anal Chem. 1998;70:341–361.
Wartewig S, Neubert RH. Pharmaceutical applications of mid-IR and Raman spectroscopy.Adv Drug Deliv Rev. 2005;57:1144–1170.
Fini G. Applications of Raman spectroscopy to pharmacy.J Raman Spectrosc. 2004;35:335–337.
Dollish FR, Fateley WG, Bentley FF.Characteristic Raman Frequencies of Organic Compounds. New York, NY: Wiley-Interscience; 1974.
Lin-Vien D, Colthup NB, Fateley WG, Grasselli JG.The Handbook of Infrared and Raman Characteristic Frequencies of Organic Molecules. Oxford, UK: Elsevier Science & Technology Books; 1991.
Bugay D. Characterization of the solid-state: spectroscopic techniques.Adv Drug Deliv Rev. 2001;48:43–65.
Vickers TJ, Mann CK, Zhu J, Chong CK. Quantitative resonance Raman spectroscopy.Appl Spectrosc Rev. 1991;26:341–375.
Tian ZQ. Surface-enhanced Raman spectroscopy: advancements and applications.J Raman Spectrosc. 2005;36:466–470.
Bell SEJ, Sirimuthu NMS. Surface-enhanced Raman spectroscopy (SERS) for sub-micromolar detection of DNA/RNA mononucleotides.J Am Cancer Soc. 2006;128:15580–15581.
Vo-Dinh T, Yan F, Wabuyele MB. Surface-enhanced Raman scattering for biomedical diagnostics and molecular imaging.Top Appl Phys. 2006;103:409–426.
Miljanic S, Frkanec L, Biljan T, Meic Z, Zinic M. Surface-enhanced Raman scattering on molecular self-assembly in nanoparticle-hydrogel composite.Langmuir. 2006;22:9079–9081.
Wood E, Sutton C, Beezer AE, Creighton JA, Davis AF, Mitchell JC. Surface enhanced Raman scattering (SERS) study of membrane transport processes.Int J Pharm. 1997;154:115–118.
Aroca RF, Alvarez-Puebla RA, Pieczonka N, Sanchez-Cortez S, Garcia-Ramos JV. Surface-enhanced Raman scattering on colloidal nanostructures.Adv Colloid Interface Sci. 2005;116:45–61.
Kneipp J, Kneipp H, McLaughlin M, Brown D, Kneipp K. In vivo molecular probing of cellular compartments with gold nanoparticles and nanoaggregates.Nano Lett. 2006;6:2225–2231.
Kneipp J, Kneipp H, Kneipp K. Two-photon vibrational spectroscopy for biosciences based on surface-enhanced hyper-Raman scattering.Proc Natl Acad Sci USA. 2006;103:17149–17153.
USP.〈1120〉 Raman Spectrophotometry USP 29-NF 24 The United States Pharmacopoeia and The National Formulary: The Official Compendia of Standards. Rockville, MD: US Pharmacopeial Convention; 2006:2983–2988.
Pinzaru SC, Pavel I, Leopold N, Kiefer W. Identification and characterization of pharmaceuticals using Raman and surface-enhanced Raman scattering.J Raman Spectrosc. 2004;35:338–346.
Huong PV. Drug analysis by Raman and micro-Raman spectroscopy.J Pharm Biomed Anal. 1986;4:811–823.
Vankeirsbilck T, Vercauteren A, Baeyens W, et al. Applications of Raman spectroscopy in pharmaceutical analysis.TrAC. 2002;21:869–877.
Strachan CJ, Rades T, Gordon KC, Rantanen J. Raman spectroscopy for quantitative analysis of pharmaceutical solids.J Pharm Pharmacol. 2007;59:179–192.
Benevides JM, Overman SA, Thomas GJ. Raman, polarized Raman and ultraviolet resonance Raman spectroscopy of nucleic acids and their complexes.J Raman Spectrosc. 2005;36:279–299.
Lambert PJ, Whitman AG, Dyson OF, Akula SM. Raman spectroscopy: the gateway into tomorrow’s virology.Virol J. 2006;3:51.
Ling J. Raman imaging microscopy—a potential cost-effective tool for drug development.Am Pharm Rev. 2005;8:44–49.
Hartschuh A, Sanchez EJ, Xie XS, Novotny L. High-resolution near-field Raman microscopy of single-walled carbon nanotubes.Phys Rev Lett. 2003;90:095503.
Li L. AbuBaker O, Shao ZJ. Characterization of poly(ethylene oxide) as a drug carrier in hot-melt extrusion.Drug Dev Ind Pharm. 2006;32:991–1002.
Bell SEJD, Andrew C, Fido LA, et al. Characterization of silicone elastomer vaginal rings containing HIV microbicide TMC120 by Raman spectroscopy.J Pharm Pharmacol. 2007;59:203–207.
Randall CS, Dinenno BK, Schultz RK, Dayter L, Konieczny M, Wunder SL. Solid-state transformation of a leukotriene antagonist.Int J Pharm. 1995;120:235–245.
Chan KLA, Fleming OS, Kazarian SG, Vassou D, Chryssikos GD, Gionis V. Polymorphism and devitrification of nifedipine under controlled humidity: a combined FT-Raman, IR and Raman microscopic investigation.J Raman Spectrosc. 2004;35:353–359.
Cao X, Sun C, Thamann TJ. A study of sulfamerazine single crystals using atomic force microscopy, transmission light microscopy, and Raman spectroscopy.J Pharm Sci. 2005;94:1881–1892.
Stoica C, Verwer P, Meekes H, Vlieg E, van Hoof PJCM, Kaspersen FM. Epitaxial 2D nucleation of the stable polymorphic form of the steroid 7αMNa on the metastable form: implications for Ostwald’s rule of stages.Int J Pharm. 2006;309:16–24.
Kojima T, Onoue S, Murase N, Katoh F, Mano T, Matsuda Y. Crystalline form information from multiwell plate salt screening by use of Raman microscopy.Pharm Res. 2006;23:806–812.
Sasic S. Raman mapping of low-content API pharmaceutical formulations, I: mapping of alprazolam in alprazolam/Xanax tablets.Pharm Res. 2007;24:58–65.
Henson MJ, Zhang L. Drug characterization in low dosage pharmaceutical tablets using Raman microscopic mapping.Appl Spectrosc. 2006;60:1247–1255.
Ling J, Weitman SD, Miller MA, Moore RV, Bovik AC. Direct Raman imaging techniques for study of the subcellular distribution of a drug.Appl Opt. 2002;41:6006–6017.
Kang E, Wang H, Kwon IK, Robinson J, Park K, Cheng J-X. In situ visualization of paclitaxel distribution and release by coherent anti-stokes Raman scattering microscopy.Anal Chem. 2006;78:8036–8043.
Sasic S, Clark DA, Mitchell JC, Snowden MJ. Raman line mapping as a fast method for analyzing pharmaceutical bead formulations.Analyst. 2005;130:1530–1536.
Tian F, Sandler N, Gordon KC, et al. Visualizing the conversion of carbamazepine in aqueous suspension with and without the presence of excipients: a single crystal study using SEM and Raman microscopy.Eur J Pharm Biopharm. 2006;64:326–335.
Choo-Smith LP, Edwards HG, Endtz HP, et al. Medical applications of Raman spectroscopy: from proof of principle to clinical implementation.Biopolymers. 2002;67:1–9.
Notingher I, Hench LL. Raman microspectroscopy: a noninvasive tool for studies of individual living cells in vitro.Expert Rev Med Devices. 2006;3:215–234.
Cheng J-X, Jia K, Eheng G, Xie XS. Laser-scanning coherent anti-Stokes Raman scattering microscopy and application to cell biology.Biophys J. 2002;83:502–509.
Taleb A, Diamond J, McGarvey JJ, Beattie JR, Toland C, Hamilton PW. Raman microscopy for the chemometric analysis of tumor cells.J Phys Chem B. 2006;110:19625–19631.
de Lange MJL, Bonn M, Müller M. Direct measurement of phase coexistence in DPPC/cholesterol vesicles using Raman spectroscopy.Chem Phys Lipids. 2007;146:76–84.
Schaeberle MD, Morris HR, Turner JF, Treado PJ. Raman chemical imaging spectroscopy.Anal Chem. 1999;71:175A-181A.
Bakker Schut TC, Witjes MJH, Sterenborg HJCM, et al. In vivo detection of dysplastic tissue by Raman spectroscopy.Anal Chem. 2000;72:6010–6018.
Chowdary MVP, Kumar KK, Kurien J, Mathew S, Krishna CM. Discrimination of normal, benign, and malignant breast tissues by Raman spectroscopy.Biopolymers. 2006;83:556–569.
Yu C, Gestl E, Eckert K, Allara D, Irudayaraj J. Characterization of human breast epithelial cells by confocal Raman microspectroscopy.Cancer Detect Prev. 2006;30:515–522.
Haka AS, Shafer-Peltier KE, Fitzmaurice M, Crowe J, Dasari RR, Feld MS. Diagnosing breast cancer by using Raman spectroscopy.Proc Natl Acad Sci USA. 2005;102:12371–12376.
Krishna CM, Kegelaerl G, Rubin S, Kartha VB, Manfait M, Sockalingum GD. Combined Fourier transform infrared and Raman spectroscopic identification approach for identification of multidrug resistance phenotype in cancer cell lines.Biopolymers. 2006;82:462–470.
Brenan CJH, Hunter IW. Confocal image properties of a confocal scanning laser visible-light FT-Raman microscope.Appl Spectrosc. 1995;49:971–976.
Breitenbach J, Schrof W, Neumann J. Confocal Raman-spectroscopy: analytical approach to solid dispersions and mapping of drugs.Pharm Res. 1999;16:1109–1113.
Noda K, Sato H, Watanabe S, Yokoyama S, Tashiro H. Efficient characterization for protein crystals using confocal Raman spectroscopy.Appl Spectrosc. 2007;61:11–18.
Caspers PJ, Williams AC, Carter EA, et al. Monitoring the penetration enhancer dimethyl sulfoxide in human stratum corneum in vivo by confocal Raman spectroscopy.Pharm Res. 2002;19:1577–1580.
Zhang G, Moore DJ, Sloan KB, Flach CR, Mendelsohn R. Imaging the prodrug-to-drug transformation of a 5-fluorouracil derivative in skin by confocal Raman microscopy.J Invest Dermatol. 2007;127:1205–1209.
Xiao C, Moore DJ, Rerek ME, Flach CR, Mendelsohn R. Feasibility of tracking phospholipid permeation into skin using infrared and Raman microscopic imaging.J Invest Dermatol. 2005;124:622–632.
Caspers PJ, Lucassen GW, Puppels GJ. Combined in vivo confocal Raman spectroscopy and confocal microscopy of human skin.Biophys J. 2003;85:572–580.
Xie C, Mace J, Dinno MA, et al. Identification of single bacterial cells in aqueous solution using confocal laser tweezers Raman spectroscopy.Anal Chem. 2005;77:4390–4397.
Chan JW, Esposito AP, Talley CE, Hollars CW, Lane SM, Huser T. Reagentless identification of single bacterial spores in aqueous solution by confocal laser tweezers Raman spectroscopy.Anal Chem. 2004;76:599–603.
Xie CG, Chen D, Li YQ. Raman sorting and identification of single living micro-organisms with optical tweezers.Opt Lett. 2005;30:1800–1802.
Chan JW, Taylor DS, Zwerdling T, Lane SM, Ihara K, Huser T. Micro-Raman spectroscopy detects individual neoplastic and normal hematopoietic cells.Biophys J. 2005;90:648–656.
Mannie MD, McConnell TJ, Xie C, Li YQ. Activation-dependent phases of T cells distinguished by use of optical tweezers and near infrared Raman spectroscopy.J Immunol Methods. 2005;297:53–60.
Deng JL, Wei Q, Zhang MH, Wang YZ, Li YQ. Study of the effect of alcohol on single human red blood cells using near-infrared laser tweezers Raman spectroscopy.J Raman Spectrosc. 2005;36:257–261.
Ward S, Perkins M, Zhang JX, et al. Identifying and mapping surface amorphous domains.Pharm Res. 2005;22:1195–1202.
Clarke FC, Jamieson MJ, Clark DA, Hammond SV, Jee RD, Moffat AC. Chemical image fusion. The synergy of FT-NIR and Raman mapping microscopy to enable a more complete visualization of pharmaceutical formulations.Anal Chem. 2001;73:2213–2220.
Ringqvist A, Taylor L, Ekelund K, Ragnarsson G, Engstrom S, Axelsson A. Atomic force microscopy analysis and confocal Raman microimaging of coated pellets.Int J Pharm. 2003;267:35–47.
Vo-Dinh T, Yan F, Wabuyele MB. Surface-enhanced Raman scattering for medical diagnostics and biological imaging.J Raman Spectrosc. 2005;36:640–647.
Howes BD, Scatragli S, Marzocchi MP, Smulevich G. Surface-enhanced resonance Raman spectroscopy of rifamycins on silver nanoparticles: insight into their adsorption mechanisms.J Raman Spectrosc. 2006;37:900–909.
Farquharson S, Shende C, Inscore FE, Maksymiuk P, Gift A. Analysis of 5-fluorouracil in saliva using surface-enhanced Raman spectroscopy.J Raman Spectrosc. 2005;36:208–212.
Rivas L, Sanchez-Cortes S, Garcia-Ramos JV. Raman structural study of thymine and its 2′-deoxy-ribosyl derivatives in solid state, aqueous solution and when adsorbed on silver nanoparticles.Phys Chem Chem Phys. 2002;4:1943–1948.
Rivas L, Sanchez-Cortes S, Garcia-Ramos JV. Conformational study of AZT in aqueous solution and adsorbed on a silver surface by means of Raman spectroscopy.J Raman Spectrosc. 2002;33:6–9.
Wang Y, Li YS, Wu J, Zhang ZX, An DQ. Surface-enhanced Raman spectra of some anti-tubercle bacillus drugs.Spectrochim Acta [A]. 2000;56:2637–2644.
Fabriciova G, Sanchez-Cortes S, Garcia-Ramos JV, Miskovsky P. Joint application of micro-Raman and surface-enhanced Raman spectroscopy to the interaction study of the antitumoral anthraquinone drugs danthron and quinizarin with albumins.J Raman Spectrosc. 2004;35:384–389.
Lee S, Kim S, Choo J, et al. Biological imaging of HEK293 cells expressing PLC1 using surface-enhanced Raman microscopy.Anal Chem. 2007;79:916–922.
Eliasson C, Engelbrektsson J, Loren A, Abrahamsson J, Abrahamsson K, Josefson M. Multivariate methodology for surface enhanced Raman chemical imaging of lymphocytes.Chemometr Intell Lab Sys. 2006;81:13–20.
Nithipatikom K, McCoy MJ, Hawi SR, Nakamoto K, Adar F, Campbell WB. Characterization and application of Raman labels for confocal Raman microspectroscopic detection of cellular proteins in single cells.Anal Biochem. 2003;322:198–207.
Strehle KR, Cialla D, Rosch P, Henkel T, Kohler M, Popp J. A reproducible surface-enhanced Raman spectroscopy approach. Online SERS measurements in a segmented microfluidic system.Anal Chem. 2007;79:1542–1547.
Jarvis RM, Brooker A, Goodacre R. Surface-enhanced Raman spectroscopy for bacterial discrimination utilizing a scanning electron microscope with a Raman spectroscopy interface.Anal Chem. 2004;76:5198–5202.
Driskell JD, Kwarta KM, Lipert RJ, Porter MD, Neill JD, Ridpath JF. Low-level detection of viral pathogens by a surface-enhanced Raman scattering based immunoassay.Anal Chem. 2005;77:6147–6154.
Deckert V, Zeisel D, Zenobi R, Vo-Dinh T. Near-field surface-enhanced Raman imaging of dye-labeled DNA with 100-nm resolution.Anal Chem. 1998;70:2646–2650.
Rasmussen A, Deckert V. Surface- and tip-enhanced Raman scattering of DNA components.J Raman Spectrosc. 2006;37:311–317.
Schweiger G. Raman scattering on single aerosol particles and on flowing aerosols: a review.J Aerosol Sci. 1990;21:483–509.
Reid JP, Meresman H, Mitchem L, Symes R. Spectroscopic studies of the size and composition of single aerosol droplets.Int Rev Phys Chem. 2007;26:139–192.
Rosen H, Novakov T. Raman-scattering and characterization of atmospheric aerosol particles.Nature. 1977;266:708–710.
Buehler MF, Allen TM, Davis EJ. Microparticle Raman spectroscopy of multicomponent aerosols.J Colloid Interface Sci. 1991;146:79–89.
Stowers M, Friedlander S. Chemical characterization of flowing polydisperse aerosols by Raman spectroscopy.Aerosol Sci Technol. 2002;36:48–61.
Vehring R, Aardahl C, Schweiger G, Davis E. The characterization of fine particles originating from an uncharged aerosol: size dependence and detection limits for Raman analysis.J Aerosol Sci. 1998;29:1045–1061.
Nelson MP, Zugates CT, Treado PJ, Casuccio GS, Exline DL, Schlaegle SF. Combining Raman chemical imaging and scanning electron microscopy to characterize ambient fine particulate matter.Aerosol Sci Technol. 2001;34:108–117.
Batonneau Y, Sobanska S, Laureyns J, Bremard C. Confocal microprobe Raman imaging of urban tropospheric aerosol particles.Environ Sci Technol. 2006;40:1300–1306.
Hopkins RJ, Reid JP. A comparative study of the mass and heat transfer dynamics of evaporating ethanol/water, methanol/water, and 1-propanol/water aerosol droplets.J Phys Chem B. 2006;110:3239–3249.
Hopkins RJ, Reid JP. Evaporation of ethanol/water droplets: examining the temporal evolution of droplet size, composition and temperature.J Phys Chem A. 2005;109:7923–7931.
Mitchem L, Hopkins RJ, Buajarem J, Ward AD, Reid JP. Comparative measurements of aerosol droplet growth.Chem Phys Lett. 2006;432:362–366.
Mitchem L, Buajarern J, Hopkins RJ, et al. Spectroscopy of growing and evaporating water droplets: exploring the variation in equilibrium droplet size with relative humidity.J Phys Chem A. 2006;110:8116–8125.
Reid JP, Mitchem L. Laser probing of single-aerosol droplet dynamics.Annu Rev Phys Chem. 2006;57:245–271.
Buehler MF, Davis EJ. A study of gas aerosol chemical reactions by microdroplet Raman spectroscopy—the bromine/1-octadecene reaction.Colloids Surf A. 1993;79:137–149.
Rassat SD, Davis EJ. Chemical reaction of sulfur dioxide with a calcium oxide aerosol particle.J Aerosol Sci. 1992;23:165–180.
Chen B, Laucks M, Davis E. Carbon dioxide uptake by hydrated lime aerosol particles.Aerosol Sci Technol. 2004;38:588–597.
Tang IN, Fung KH. Characterization of inorganic salt particles by Raman spectroscopy.J Aerosol Sci. 1989;20:609–617.
Davis EJ, Rassat SD, Foss W. Measurement of aerosol/gas reaction rates by microparticle Raman spectroscopy.J Aerosol Sci. 1992;23:429–432.
Davis EJ, Aardahl CL, Widmann JF. Raman studies of aerosol chemical reactions.J Dispersion Sci Technol. 1998;19:293–309.
Zhang JX, Aiello D, Aker PM. Hydrogen-bonding at the aerosol interface.J Phys Chem A. 1995;99:721–730.
Fung KH, Tang IN. Aerosol particle analysis by resonance Raman spectroscopy.J Aerosol Sci. 1992;23:301–307.
Mitchem L, Buajarern J, Ward AD, Reid JP. A strategy for characterizing the mixing state of immiscible aerosol components and the formation of multiphase aerosol particles through coagulation.J Phys Chem B. 2006;110:13700–13703.
Spumy KR. On the chemical detection of bioaerosols.J Aerosol Sci. 1994;25:1533–1547.
Laucks ML, Roll G, Schweiger G, Davis EJ. Physical and chemical (Raman) characterization of bioaerosols—pollen.J Aerosol Sci. 2000;31:307–319.
Pan YL, Boutou V, Bottiger J, Zhang S, Wolf JP, Chang R. A puff of air sorts bioaerosols for pathogen identification.Aerosol Sci Technol. 2004;38:598–602.
Sengupta A, Laucks ML, Dildine N, Drapala E, Davis EJ. Bioaerosol characterization by surface-enhanced Raman spectroscopy (SERS).J Aerosol Sci. 2005;36:651–664.
Sengupta A, Brar N, Davis EJ. Bioaerosol detection and characterization by surface-enhanced Raman spectroscopy.J Colloid Interface Sci. 2007;309:36–43.
Kalasinsky KS, Hadfield T, Shea AA, et al. Raman chemical imaging spectroscopy reagentless detection and identification of pathogens: signature development and evaluation.Anal Chem. 2007;79:2658–2673.
Zhang XY, Young MA, Lyandres O, Van Duyne RP. Rapid detection of an anthrax biomarker by surface-enhanced Raman spectroscopy.J Am Cancer Soc. 2005;127:4484–4489.
Vincent J, Revak S, Cochrane C, Levin I. Raman spectroscopic studies of model human pulmonary surfactant systems: phospholipid interactions with peptide paradigms for the surfactant protein SP-B.Biochemistry. 1991;30:8395–8401.
Vincent JS, Revak SD, Cochrane CD, Levin IW. Interactions of model human pulmonary surfactants with a mixed phospholipid bilayer assembly—Raman spectroscopic studies.Biochemistry. 1993;32:8228–8238.
Hickey AJ, Mansour HM. Formulation challenges of powders for the delivery of small molecular weight molecules as aerosols. In: Rathbone MJ, Hadgraft J, Roberts MS, Lane M, eds.Modified-Release Drug Delivery Technology. 2nd ed. New York, NY: Informa Healthcare; In press.
Krafft C, Knetschke T, Funk RHW, Salzer R. Studies on stress-induced changes at the subcellular level by Raman microspectroscopic mapping.Anal Chem. 2006;78:4424–4429.
Kaminaka S, Yamazaki H, Ito T, Kohda E, Hamaguchi HO. Near-infrared Raman spectroscopy of human lung tissues: possibility of molecular-level cancer diagnosis.J Raman Spectrosc. 2001;32:139–141.
Kaminaka S, Ito T, Yamazaki H, Kohda E, Hamaguchi H. Near-infrared multichannel Raman spectroscopy toward real-time in vivo cancer diagnosis.J Raman Spectrosc. 2002;33:498–502.
Koljenovic S, Schut TCB, van Meerbeeck JP, et al. Raman microspectroscopic mapping studies of human bronchial tissue.J Biomed Opt. 2004;9:1187–1197.
Huang Z, McWilliams A, Lam S, et al. Effect of formalin fixation on the near-infrared Raman spectroscopy of normal and cancerous human bronchial tissues.Int J Oncol. 2003;23:649–655.
Huang Z, McWilliams A, Lui H, McLean DI, Lam S, Zeng HS. Near-infrared Raman spectroscopy for optical diagnosis of lung cancer.Int J Cancer. 2003;107:1047–1052.
Min YK, Yamamoto T, Kohda E, Ito T, Hamaguchi H. 1064 nm near-infrared multichannel Raman spectroscopy of fresh human lung tissues.J Raman Spectrosc. 2005;36:73–76.
Kreher C, Bootz W, Niemann M, Scaffidi L, Spallek MW. Foreign particle characterization in inhalation drug products: a critical comparison of methods and techniques. In: Dalby RN, Byron PR, Suman JD, Peart J, Farr SJ, eds.Respiratory Drug Delivery IX. Palm Springs, CA: Davis Healthcare International Publishing; 2004:373–376.
Dem C, Egen M, Krueger M, Popp J. Understanding the spray dry design process through single droplet investigations. In: Dalby RN, Byron PR, Suman JD, Peart J, Farr SJ, eds.Respiratory Drug Delivery X. Boca Raton, FL: Davis Healthcare International Publishing; 2006:257–266.
Niemann M, Fusser M, Scaffidi L. A critical comparison: particle counting with light obscuration and automated Raman microscopy. In: Dalby RN, Byron PR, Suman JD, Peart J, Farr SJ, eds.Respiratory Drug Delivery X. Boca Raton, FL: Davis Healthcare International Publishing; 2006:529–532.
Hickey AJ, Mansour HM, Telko MJ, et al. Physical characterization of component particles included in dry powder inhalers, I: strategy review and static characteristics.J Pharm Sci. 2007;96:1282–1301.
Hickey AJ, Mansour HM, Telko MJ, et al. Physical characterization of component particles included in dry powder inhalers, II: dynamic characteristics.J Pharm Sci. 2007;96:1302–1319.
Ticehurst MD, York P, Rowe RC, Dwivedi SK. Characterisation of the surface properties ofα-lactose monohydrate with inverse gas chromatography, used to detect batch variation.Int J Pharm. 1996;141:93–99.
Murphy BM, Prescott SW, Larson I. Measurement of lactose crystallinity using Raman spectroscopy.J Pharm Biomed Anal. 2005;38:186–190.
Niemela P, Paallysaho M, Harjunen P, et al. Quantitative analysis of amorphous content of lactose using CCD-Raman spectroscopy.J Pharm Biomed Anal. 2005;37:907–911.
Kirk JH, Dann SE, Blatchford CG. Lactose: a definitive guide to polymorph determination.Int J Pharm. 2007;334:103–114.
Ticehurst MD, Rowe RC, York P. Determination of the surface properties of two batches of salbutamol sulphate by inverse gas chromatography.Int J Pharm. 1994;111:241–249.
Brown AB, York P, Williams AC, Edwards HGM, Worthington H. Solid-state characterization of salbutamol salts using FT-Raman and SSNMR spectroscopy.J Pharm Pharmacol. 1993;45:1135.
Moshashaée S, Bisrat M, Forbes RT, Quinn ÉA, Nyqvist H, York P. Supercritical fluid processing of proteins: lysozyme precipitation from aqueous solution.J Pharm Pharmacol. 2003;55:185–192.
Quinn EA, Forbes RT, Williams AC, Oliver MJ, McKenzie L, Purewal TS. A Raman spectroscopic study of the compatibility of proteins with hydrofluoroalkane propellants. In: Dalby RN, Byron PR, Suman JD, Peart J, Farr SJ, eds.Respiratory Drug Delivery VII. Tarpon Springs, FL: Davis Healthcare International Publishing; 2000:581–584.
Quinn EA, Forbes RT, Williams AC, Oliver MJ, McKenzie L, Purewal TS. Protein conformational stability in the hydrofluoroalkane propellants tetrafluoroethane and heptafluoropropane analysed by Fourier transform Raman spectroscopy.Int J Pharm. 1999;186:31–41.
Guo C, Doub WH. Use of Raman imaging for determination of the particle size distribution (PSD) of active pharmaceutical ingredients (APIs) in metered dose inhalers. In: Dalby RN, Byron PR, Suman JD, Peart J, Farr SJ, eds.Respiratory Drug Delivery X. Boca Raton, FL: Davis Healthcare International Publishing; 2006:617–620.
Waligorski A, Doub WH, Adams WP, et al. Raman chemical imaging for drugs and excipients in aqueous suspension nasal spray formulations. In: Dalby RN, Byron PR, Suman JD, Pert J, Farr SJ, eds.Respiratory Drug Delivery X. 541–544.
Doub WH, 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;24:934–945.
Vehring R. Red-excitation dispersive Raman spectroscopy is a suitable technique for solid-state analysis of respirable pharmaceutical powders.Appl Spectrosc. 2005;59:286–292.
Chan H, Clark AR, Feeley J, et al. Physical stability of salmon calcitonin spray-dried powders for inhalation.J Pharm Sci. 2004;93:792–804.
Vehring R. Linear Raman spectroscopy on aqueous aerosols: influence of nonlinear effects on detection limits.J Aerosol Sci. 1998;29:65–79.
Steele DF, Young PM, Price R, Smith T, Edge S, Lewis D. The potential use of Raman mapping to investigatein vitro deposition of combination pressurized metered-dose inhalers.AAPS J. 2004;6:E32.
Hickey AJ.Inhalation Aerosols: The Physiological Basis for Therapy. New York, NY: Informa Healthcare; 2007.
Theophilus A, Moore A, Prime D, Rossomanno S, Whitcher B, Chrystyn H. Co-deposition of salmeterol and fluticasone propionate by a combination inhaler.Int J Pharm. 2006;313:14–22.
Michael Y, Snowden MJ, Chowdhry BZ, Ashurst IC, Davies-Cutting CJ, Riley T. Characterisation of the aggregation behaviour in a salmeterol and fluticasone propionate inhalation aerosol system.Int J Pharm. 2001;221:165–174.
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Mansour, H.M., Hickey, A.J. Raman characterization and chemical imaging of biocolloidal self-assemblies, drug delivery systems, and pulmonary inhalation aerosols: A review. AAPS PharmSciTech 8, 99 (2007). https://doi.org/10.1208/pt0804099
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DOI: https://doi.org/10.1208/pt0804099