AAPS PharmSciTech

, 20:109 | Cite as

Brillouin Light Scattering: Development of a Near Century-Old Technique for Characterizing the Mechanical Properties of Materials

  • Aditya B. Singaraju
  • Dherya Bahl
  • Lewis L. StevensEmail author
Review Article Theme: Advances in PAT, QbD, and Material Characterization
Part of the following topical collections:
  1. Theme: Advances in PAT, QbD, and Material Characterization


Brillouin light scattering (BLS), a technique theoretically described nearly a century back by the French physicist Léon Brillouin in 1922, is a light-scattering method for determining the mechanical properties of materials. This inelastic scattering method is described by the Bragg diffraction of light from a propagating fluctuation in the local dielectric. These fluctuations arise spontaneously from thermally populated sound waves intrinsic to all materials, and thus BLS may be broadly applied to transparent samples of any phase. This review begins with a brief historical overview of the development of BLS, from its theoretical prediction to the current state of the art, and notes specific technological advancements that enabled the development of BLS. Despite the broad utility of BLS, no commercial spectrometer is currently available for purchase, but rather individual components are assembled to suit a specific application. Central to any BLS spectrometer is the interferometer, and its performance characteristics—scanning or non-scanning, multi-passing, and stabilization—are critical considerations for spectrometer design. Consistent with any light-scattering method, the frequency shift is a key observable in BLS, and we summarize the connection of this measurement to evaluate the mechanical properties of materials. With emphasis toward pharmaceutical materials analysis, we introduce the traditional BLS approach for single-crystal elasticity, and this is followed by a discussion of more recent developments in powder BLS. We conclude our review with a perspective on future developments in BLS that may enable BLS as a novel addition to the current catalog of process analytical technologies.

Key Words

mechanical properties pharmaceutical materials elastic constants Brillouin scattering powders 



  1. 1.
    Siddiqui MR, Al-Othman ZA, Rahman N. Analytical techniques in pharmaceutical analysis: a review. Arab J Chem. 2017;10:S1409–21.CrossRefGoogle Scholar
  2. 2.
    Yu LX, Lionberger RA, Raw AS, D'Costa R, Wu H, Hussain AS. Applications of process analytical technology to crystallization processes. Adv Drug Deliv Rev. 2004;56:349–69.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Rodriquez LO, Alves TP, Cardoso JP, Menezes JC. Improving drug manufacturing with process analytical technology. IDrugs. 2006;9:44–8.Google Scholar
  4. 4.
    Jamroqiewicz M. Application of the near-infrared spectroscopy in the pharmaceutical technology. J Pharm Biomed Anal. 2012;10:66.Google Scholar
  5. 5.
    Reich G. Near-infrared spectroscopy and imaging: basic principles and pharmaceutical applications. Adv Drug Deliv Rev. 2005;57:1109–43.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Gowen AA, O'Donnell CP, Cullen PJ, Bell SE. Recent applications of chemical imaging to pharmaceutical process monitoring and quality control. Eur J Pharm Biopharm. 2008;69:10–22.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Gendrin C, Roggo Y, Collet C. Pharmaceutical applications of vibrational chemical imaging and chemometrics: a review. J Pharm Biomed Anal. 2008;48:533–53.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Silva AF, Burggraeve A, Denon Q, Van der Meeran P, Sandler N, Van Den Kerkhof T, et al. Particle sizing measurements in pharmaceutical applications: comparison of in-process methods versus off-line methods. Eur J Pharm Biopharm. 2013;85:1006–18.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Patil SM, Keire DA, Chen K. Comparison of NMR and dynamic light scattering for measuring diffusion coefficients of formulated insulin: implications for particle size distribution measurements in drug products. AAPS J. 2017;19:1760–6.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Chan MY, Dowling QM, Sivananthan SJ, Kramer RM. Particle sizing of nanoparticle adjuvant formulations by dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). Methods Mol Biol. 2017;1494:239–52.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    De Beer TR, Bodson C, Dejaegher B, Walczak B, Vercruysse P, Burggraeve A, et al. Raman spectroscopy as a process analytical technique technology (PAT) tool for the in-line monitoring and understanding of a powder blending process. J Pharm Biomed Anal. 2008;48:772–9.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    De Beer T, Burggraeve A, Fonteyne M, Saerens L, Remon JP, Vervaet C. Near infrared and Raman spectroscopy for the in-process monitoring of pharmaceutical production processes. Int J Pharm. 2011;417:32–47.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Li YS, Church JS. Raman spectroscopy in the analysis of food and pharmaceutical nanomaterials. J Food Drug Anal. 2014;22:29–48.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Berghaus K, Zhang J, Yun SH, Scarcelli G. High-finesse sub-GHz-resolution spectrometer employing VIPA etalons of different dispersion. Opt Lett. 2015;40:4436–9.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Scarcelli G, Yun SH. Confocal Brillouin microscopy for three-dimensional mechanical imaging. Nat Photonics. 2008;2:39–43.CrossRefGoogle Scholar
  16. 16.
    Scarcelli G, Kim P, Yun SH. In vivo measurement of age-related stiffening in the crystalline lens by Brillouin optical spectroscopy. Biophys J. 2011;101:1539–45.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Coker Z, Troyanova-Wood M, Traverso AJ, Yakupov T, Utegulov ZN, Yakolev VV. Assessing performance of modern Brillouin spectrometers. Opt Express. 2018;26:2400–9.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Meng Z, Bustamante Lopez SC, Meissner KE, Yakovlev VV. Subcellular measurements of mechanical and chemical properties using dual Raman-Brillouin microspectroscopy. J Biophotonics. 2016;9:201–7.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Kuok MH, Lim HS, Ng SC, Liu NN, Wang ZK. Brillouin study of the quantization of acoustic modes in nanospheres. Phys Rev Lett. 2003;90:255502.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Mohapatra H, Kruger TM, Lansakara TI, Tivanski AV, Stevens LL. Core and surface microgel mechanics are differentially sensitive to alternative crosslinking concentrations. Soft Matter. 2017;13:5684–95.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Faurie D, Girodon-Boulandet N, Kaladjian A, Challali F, Abadias G, Djemia P. Setup for high-temperature surface Brillouin light scattering: application to opaque thin films and coatings. Rev Sci Instrum. 2017;88:0293.CrossRefGoogle Scholar
  22. 22.
    Pochylski M, Gapinski J. Simple way to analyze Brillouin spectra from turbid liquids. Opt Lett. 2015;40:1456–9.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Brillouin L. Diffusion de la lumiere et des rayons X par un corps transparent homogene: Influence de l'agitation thermique. Ann Phys (Paris). 1922:88–122.Google Scholar
  24. 24.
    Mandelstam LI. Light scattering by inhomogeneous media. Zh Russ Fiz-Khim Ova 1926;58:381.Google Scholar
  25. 25.
    Gross E. Change of wave-length of light due to elastic heat waves at scattering in liquids. Nature. 1930;126:201–2.CrossRefGoogle Scholar
  26. 26.
    Gross E. The splitting of spectral lines at scattering of light by liquids. Nature. 1930;126:400.CrossRefGoogle Scholar
  27. 27.
    Traverso AJ, Thompson JV, Steelman ZA, Meng Z, Scully MO, Yakovlev VV. Dual Raman-Brillouin microscope for chemical and mechanical characterization and imaging. Anal Chem. 2015;87:7519–23.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Meng Z, Thakur T, Chitrakar C, Jaiswal MK, Gaharwar AK, Yakolev VV. Assessment of local heterogeneity in mechanical properties of nanostructured hydrogel networks. ACS Nano. 2017;11:7690–6.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Brewer RG, Rieckhoff KE. The ruby laser as a Brillouin light amplifier. Appl Phys Lett. 1964;5:127–8.CrossRefGoogle Scholar
  30. 30.
    Chiao RY, Stoicheff BP. Brillouin scattering in liquids excited by the helium-neon maser. J Opt Soc Am. 1964;54:1286–7.CrossRefGoogle Scholar
  31. 31.
    Cummins HZ, Gammon RW. Rayleigh and Brillouin scattering in benzene: depolarization factors. Appl Phys Lett. 1965;6:171–3.CrossRefGoogle Scholar
  32. 32.
    Hakim SEA, Comley WJ. Acoustic velocity dispersion in some nonassociated organic liquids. Nature. 1965;208:1082–3.CrossRefGoogle Scholar
  33. 33.
    Venkateswaran CS. Interferometric studies of light scattering in mobile liquids. P Indian Acad Sci A. 1942;15A:322–37.CrossRefGoogle Scholar
  34. 34.
    Grimsditch MH, Ramdas AK. Brillouin scattering in diamond. Phys Rev B. 1975;11:3139–48.CrossRefGoogle Scholar
  35. 35.
    Asenbaum A. Computer-controlled Fabry-Perot interferometer for Brillouin spectroscopy. Appl Opt. 1979;4:363–5.Google Scholar
  36. 36.
    Roychoudhuri C, Hercher M. Stable multipass Fabry-Perot interferometer: design and analysis. Appl Opt. 1977;16:2514–20.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Dil JG, Van Hijningen NCJA, Van Dorst F. Aarts RM tandem multipass Fabry-Perot interferometer for Brillouin scattering. Appl Opt. 1981;20:1374–81.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Krueger JK, Kimmich R, Sandercock J, Unruh HG. The thermal behavior of n-tetracosane and low molecular weight polyethylene studied by NMR and a refined Brillouin scattering technique. Polym Bull. 1981;5:615–21.Google Scholar
  39. 39.
    Maret G, Oldenbourg R, Winterling G, Dransfeld K, Rupprecht A. Velocity of high frequency sound waves in oriented DNA fibers and films determined by Brillouin scattering. Colloid Polym Sci. 1979;257:1017–20.CrossRefGoogle Scholar
  40. 40.
    Randall J, Vaughan JM. Brillouin scattering in systems of biological significance. Philos T R Soc A. 1979;293:341–8.CrossRefGoogle Scholar
  41. 41.
    Cusack S, Miller A. Determination of the elastic constants of collagen by Brillouin light scattering. J Mol Biol. 1979;135:39–51.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Zanoni R, Naselli C, Bell J, Stegeman G, Sprague R, Seaton C, et al. Brillouin spectroscopy of Langmuir-Blodgett films. Thin Solid Films. 1985;134:179–86.CrossRefGoogle Scholar
  43. 43.
    Koski KJ, Akhenblit P, McKiernan K, Yarger JL. Non-invasive determination of the complete elastic moduli of spider silks. Nat Mater. 2013;12:262–7.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Gehrsitz S, Sigg H, Siegwart H, Krieger M, Heine C, Morf R, et al. Tandem triple-pass Fabry-Perot interferometer for applications in the near infrared. Appl Opt. 1997;36:5355–61.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Bottari C, Comez L, Paolantoni M, Corezzi S, D'Amico F, Gessini A, et al. Hydration properties and water structure in aqueous solutions of native and modified cyclodextrins by UV Raman and Brillouin scattering. J Raman Spectrosc. 2018;49:1076–85.CrossRefGoogle Scholar
  46. 46.
    Koski KJ, Yarger JL. Brillouin imaging. Appl Phys Lett. 2005;87:061903.CrossRefGoogle Scholar
  47. 47.
    Meng Z, Petrov GI, Yakolev VV. Flow cytometry using Brillouin imaging and sensing via time-resolved optical (BISTRO) measurements. Analyst. 2015;140:7160–4.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Troyanova-Wood M, Gobbell C, Meng Z, Gashev AA, Yakolev VV. Optical assessment of changes in mechanical and chemical properties of adipose tissue in diet-induced obese rats. J Biophotonics. 2017;10:1694–702.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Scarcelli G, Pineda R, Yun SH. Brillouin optical microscopy for corneal biomechanics. Invest Ophthalmol Vis Sci. 2012;53:185–90.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Yun SH, Chernyak D. Brillouin microscopy: assessing ocular tissue biomechanics. Curr Opin Ophthalmol. 2018;29:299–305.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Bottani CE, Fioretto D. Brillouin scattering of phonons in complex materials. Adv Phys X. 2018;3:1467281.Google Scholar
  52. 52.
    Mueller S, Sandrin L. Liver stiffness: a novel parameter for the diagnosis of liver disease. Hepat Med. 2010;2:49–67.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Wells RG. Tissue mechanics and fibrosis. Biochim Biophys Acta. 1832;2013:884–90.Google Scholar
  54. 54.
    Fernandes C, Suares D, Yergen MC. Tumor microenvironment targeted nanotherapy. Front Pharmacol. 2018;9:1230.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Palombo C, Kozakova M. Arterial stiffness, atheroschlerosis and cardiovascular risk: pathophysiologic mechanisms and emerging clinical indications. Vasc Pharmacol. 2016;77:1–7.CrossRefGoogle Scholar
  56. 56.
    Meng Z, Basagaoglu B, Yakovlev VV. Atherosclerotic plaque detection by confocal Brillouin and Raman microscopies. in Proc. SPIE 9303, Photonic therapeutics and diagnostics XI, San Francisco, 2015.Google Scholar
  57. 57.
    Antonacci G, Pedrigi RM, Kondiboyina A, Mehta VV, de Silva R, Paterson C, et al. Quantification of plaque stiffness by Brillouin microscopy in experimental thin cap fibroatheroma. J R Soc Interface. 2015;12:20150843.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Weaver VM. Cell and tissue mechanics: the new cell biology frontier. Mol Biol Cell. 2017;28:1815–8.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Barnes JM, Przybyla L, Weaver VM. Tissue mechanics regulate brain development, homeostasis and disease. J Cell Sci. 2017;130:71–82.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Butler DL, Goldstein SA, Guldberg RE, Guo XE, Kamm R, Laurencin CT, et al. The impact of biomechanics in tissue engineering and regenerative medicine. Tissue Eng Part B Rev. 2009;15:477–84.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Sakamoto M, Kawabe M, Matsukawa M, Koizumi N, Ohtori N. Measurement of wave velocity in bovine bone tissue by micro-Brillouin scattering. Jpn J Appl Phys. 2008;47:4205–8.CrossRefGoogle Scholar
  62. 62.
    Mathieu V, Fukui K, Matsukawa M, Kawabe K, Vayron R, Soffer E, et al. Micro-Brillouin scattering measurements in mature and newly formed bone tissue surrounding an implant. J Biomech Eng. 2011;133:021006.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Akilbekova D, Ogay V, Yakupov T, Sarsenova M, Umbayev B, Tazhin K, et al. Brillouin spectroscopy and radiography for assessment of viscoelastic and regenerative properties of mammalian bone. J Biomed Opt. 2018;23:1–11.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Ingber DE. Cellular mechanotransduction: putting all the pieces together again. FASEB J. 2006;20:811–27.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Wang N. Review of cellular mechanotransduction. J Phys D Appl Phys. 2017;50:233002.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Silver FH, Siperko LM. Mechanosensing and mechanochemical transduction: how is mechanical energy sensed and converted into chemical energy in an extracellular matrix? Crit Rev Biomed Eng. 2003;31:255–331.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Fletcher DA, Mullins RD. Cell mechanics and the cytoskeleton. Nature. 2010;463:485–92.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Xu W, Mezencev R, Kim B, Wang L, McDonald J, Sulchek T. Cell stiffness is a biomarker of the metastatic potential of ovarian cancer. PLoS One. 2012;7:e46609.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Lekka M. Discrimination between normal and cancerous cells using AFM. BioNanoSci. 2016;6:65–80.CrossRefGoogle Scholar
  70. 70.
    Islam M, Mezencev R, McFarland B, Brink H, Campbell B, Tasadduq B, et al. Microfluidic cell sorting by stiffness to examine heterogenic responses of cancer cells to chemotherapy. Cell Death Dis. 2018;9:239.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Zoellner H, Paknejad N, Manova K, Moore M. A novel cell-stiffness-fingerprinting analysis by scanning atomic force microscopy: comparison of fibroblasts and diverse cancer cell lines. Histochem Cell Biol. 2015;144:533–42.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Kilpatrick JI, Revenko I, Rodriquez BJ. Nanomechanics of cells and biomaterials studied by atomic force microscopy. Adv Healthc Mater. 2015;4:2456–74.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Scarcelli G, Polacheck WJ, Nia HT, Patel K, Grodzinsky AJ, Kamm RD, et al. Noncontact three-dimensional mapping of intracellular hydromechanical properties by Brillouin microscopy. Nat Methods. 2015;12:1132–4.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Meng Z, Traverso AJ, Ballmann CW, Troyanova-Wood MA, Yakovlev VV. Seeing cells in a new light: a renaissance of Brillouin spectroscopy. Adv Opt Photon. 2016;8:300–26.CrossRefGoogle Scholar
  75. 75.
    Antonacci G, Braakman S. Biomechanics of subcellular structures by non-invasive Brillouin microscopy. Sci Rep. 2016;6:37217.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Mattana S, Mattarelli M, Urbanelli L, Sagini K, Emiliani C, Serra MD, et al. Non-contact mechanical and chemical analysis of single living cells by microspectroscopic techniques. Light Sci Appl. 2018;7:17139.PubMedCentralCrossRefGoogle Scholar
  77. 77.
    Basoli F, Giannitelli SM, Gori M, Mozetic P, Bonfanti A, Trombetta M, et al. Biomechanical characterization at the cell scale: present and prospects. Front Physiol. 2018;15:1449.CrossRefGoogle Scholar
  78. 78.
    Guo P, Liu D, Subramanyam K, Wang B, Yang J, Huang J, et al. Nanoparticle elasticity directs tumor uptake. Nat Commun. 2018;9:130.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Anselmo AC, Zhang M, Kumar S, Vogus DR, Menegatti S, Helgeson ME, et al. Elasticity of nanoparticles influences their blood circulation, phagocytosis, endocytosis, and targeting. ACS Nano. 2015;9:3169–77.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Anselmo AC, Mitragotri S. Impact of particle elasticity on particle-based drug delivery systems. Adv Drug Deliv Rev. 2017;108:51–67.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Cheng W, Wang JJ, Jonas U, Steffen W, Fytas G, Penciu R, et al. The spectrum of vibrational modes in soft opals. J Chem Phys. 2005;123:121104.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Still T, Mattarelli M, Kiefer D, Fytas G, Montagna M. Eigenvibrations of submicrometer colloidal spheres. J Phys Chem Lett. 2010;1:2440–4.CrossRefGoogle Scholar
  83. 83.
    Still T, Cheng W, Retsch M, Jonas U, Fytas G. Colloidal systems: a promising material class for tailoring sound propagation at high frequencies. J Phys:Condens Matter. 2008;20:404203.Google Scholar
  84. 84.
    Mattarelli M, Montagna M, Still T, Schneider D, Fytas G. Vibration spectroscopy of weakly interacting mesoscopic colloids. Soft Matter. 2012;8:4235–43.CrossRefGoogle Scholar
  85. 85.
    Love AEH. A treatise on the mathematical theory of elasticity. New York: Dover Publications; 1944.Google Scholar
  86. 86.
    Cummins HZ, Schoen PE. in Laser Handbook. Amsterdam: North Holland Publishing Co.; 1971. p. E1.Google Scholar
  87. 87.
    Dil JG. Brillouin scattering in condensed matter. Rep Prog Phys. 1982;45:285–334.CrossRefGoogle Scholar
  88. 88.
    Chu B. Laser scattering. J Chem Ed. 1968;45:224–30.CrossRefGoogle Scholar
  89. 89.
    Kruger JK, Marx A, Peetz L, Roberts R, Unruh HG. Simultaneous determination of elastic and optical properties of polymers by high performance Brillouin spectroscopy using different scattering geometries. Colloid Polym Sci. 1986;264:403–14.CrossRefGoogle Scholar
  90. 90.
    Xu J, Ren X, Gong W, Dai R, Liu D. Measurement of the bulk viscosity of liquid by Brillouin scattering. Appl Opt. 2003;42:6704–9.PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Ballmann CW, Meng Z, Traverso AJ, Scully MO, Yakovlev VV. Impulsive Brillouin microscopy. Optica. 2017;4:124–8.CrossRefGoogle Scholar
  92. 92.
    Bencivenga F, Battistoni A, Fioretto D, Gessini A, Sandercock JR, Masciovecchio C. A high resolution ultraviolet Brillouin scattering set-up. Rev Sci Instrum. 2012;83:103102.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Antonacci G, de Turris V, Rosa A, Ruocco G. Background-deflection Brillouin microscopy reveals altered biomechanics of intracellular stress granules by ALS protein FUS. Commun Bio. 2018;1:139.CrossRefGoogle Scholar
  94. 94.
    Fiore A, Zhang J, Shao P, Yun SH, Scarcelli G. High-extinction virtually imaged phased array-based Brillouin spectroscopy of turbid biological media. Appl Phys Lett. 2016;108:203701.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Meng Z, Yakovlev VV. Precise determination of Brillouin scattering spectrum using a virtually imaged phase array (VIPA) spectrometer and charge-coupled device (CCD) camera. Appl Spectrosc. 2016;70:1356–63.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Abell BC, Shao S, Pyrak-Nolte LJ. Measurement of elastic constants in anisotropic media. Geophysics. 2014;79:D349–62.CrossRefGoogle Scholar
  97. 97.
    Newnham R. Properties of materials. New York: Oxford University Press; 2005.Google Scholar
  98. 98.
    Nye JF. Physical properties of crystals. New York: Oxford University Press; 1957.Google Scholar
  99. 99.
    Karki S, Friscic T, Fabian L, Laity PR, Day GR, Jones W. Improving mechanical properties of crystalline solids by cocrystal formation: new compressible forms of paracetamol. Adv Mater. 2009;21:3905–9.CrossRefGoogle Scholar
  100. 100.
    Beyer T, Day GM, Price SL. The prediction, morphology, and mechanical properties of polymorphs of paracetamol. J Am Chem Soc. 2001;123:5086–94.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Ortiz AU, Boutin A, Fuchs AH, Coudert FX. Anisotropic elastic properties of flexible metal-organic frameworks: how soft are soft porous crystals? Phys Rev Lett. 2012;109:195502.PubMedCrossRefPubMedCentralGoogle Scholar
  102. 102.
    Turley J, Sines G. The anisotropy of Young’s modulus, shear modulus and Poisson’s ratio in cubic materials. J Phys D:Appl Phys. 1971;4:264–71.CrossRefGoogle Scholar
  103. 103.
    Mohapatra H, Eckhardt CJ. Elastic constants and related mechanical properties of the monoclinic polymorph of the carbamazepine molecular crystal. J Phys Chem B. 2008;112:2293–8.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Eros S, Reitz JR. Elastic constants by the ultrasonic pulse echo method. J Appl Phys. 1958;29:683–6.CrossRefGoogle Scholar
  105. 105.
    Zeng Z, Tan JC. AFM nanoindentation to quantify mechanical properties of nano- and micron-sized crystals of a metal-organic framework. ACS Appl Mater Interfaces. 2017;9:39839–54.PubMedCrossRefPubMedCentralGoogle Scholar
  106. 106.
    Stevens LL, Hooks DE, Migliori A. A comparative evaluation of elasticity in pentaerythritol tetranitrate using Brillouin scattering and resonant ultrasound spectroscopy. J Appl Phys. 2010;108:053512.CrossRefGoogle Scholar
  107. 107.
    Hernandez J, Li G, Cummins HZ, Callender RH. Low-frequency light-scattering spectroscopy of powders. J Opt Soc Am B. 1996;13:1130–4.CrossRefGoogle Scholar
  108. 108.
    Singaraju AB, Nguyen K, Jain A, Haware RV, Stevens LL. Aggregate elasticity, crystal structure and tableting performance for p-aminobenzoic acid and a series of its benzoate esters. Mol Pharm. 2016;13:3794–806.PubMedCrossRefPubMedCentralGoogle Scholar
  109. 109.
    Singaraju AB, Iyer M, Haware RV, Stevens LL. Caffeine co-crystal mechanics evaluated with a combined structural and spectroscopic approach. Cryst Growth Des. 2016;16:4383–91.CrossRefGoogle Scholar
  110. 110.
    Almarsson O, Zaworotko MJ. Crystal engineering of the composition of pharmaceutical phases. Do pharmaceutical co-crystals represent a new path to improve medicines? Chem Commun. 2004;17:1889–96.CrossRefGoogle Scholar
  111. 111.
    Steed JW. The role of co-crystals in pharmaceutical design. Trends Pharmacol Sci. 2013;34:185–93.PubMedCrossRefPubMedCentralGoogle Scholar
  112. 112.
    Stephen Chan HC, Kendrick J, Neumann MA, Leusen FJJ. Towards ab initio screening of co-crystal formation through lattice energy calculations and crystal structure prediction of multi-component crystals. CrystEngComm. 2013;15:3799–807.CrossRefGoogle Scholar
  113. 113.
    Desiraju GR. Crystal engineering: from molecule to crystal. J Am Chem Soc. 2013;135:9952–67.PubMedCrossRefPubMedCentralGoogle Scholar
  114. 114.
    Singaraju AB, Nguyen K, Swenson DC, Iyer M, Haware RV, Stevens LL. Reorganized, weak C-HO interactions directly modify the mechanical properties and compaction performance of a series of nitrobenzoic acids. CrystEngComm. 2017;19:2526–35.CrossRefGoogle Scholar
  115. 115.
    Singaraju AB, Nguyen K, Gawedski P, Herald F, Meyer G, Wentworth D, et al. Combining crystal structure and interaction topology for interpreting functional molecular solids: a study of theophylline cocrystals. Cryst Growth Des. 2017;17:6741–51.CrossRefGoogle Scholar

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© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  1. 1.Division of Pharmaceutics and Translational Therapeutics, College of PharmacyThe University of IowaIowa CityUnited States of America

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