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Pharmaceutical Research

, Volume 34, Issue 2, pp 462–478 | Cite as

Effects of Excipient Interactions on the State of the Freeze-Concentrate and Protein Stability

  • Sampreeti Jena
  • Jacqueline Horn
  • Raj Suryanarayanan
  • Wolfgang Friess
  • Alptekin Aksan
Research Paper

Abstract

Purpose

The physical state of excipients in freeze-dried formulations directly affects the stability of the active pharmaceutical ingredient (API). Crystallization of trehalose and mannitol in frozen solutions has been shown to be a function of composition. However, to date a detailed study of the effect of concentrations of the API and other excipients on the crystallinity of mannitol and trehalose in frozen solutions has not been reported.

Methods

The crystallinity of mannitol and trehalose in frozen solutions was characterized by Differential Scanning Calorimetry, X-ray diffractometry, and FTIR spectroscopy. The secondary structure of BSA was probed by FTIR, and Circular Dichroism spectroscopy in frozen and thawed solutions, respectively.

Results

Trehalose crystallization was accompanied by unfolding of BSA. BSA delayed and reduced the extent of mannitol and trehalose crystallization. Similar effects were observed upon adding D2O (≥5% w/w) and low concentrations of polysorbate 20 (≤0.2% w/w) with retention of BSA in its native conformation. At high BSA to trehalose mass ratio, the protein could stabilize itself in the frozen state, but unfolded upon thawing.

Conclusions

The API and other excipients, in a concentration-dependent manner, influenced the physical state of the freeze concentrate as well as the stability of the API.

KEY WORDS

crystallization freeze-drying glass transition mannitol trehalose 

Abbreviations

API

Active pharmaceutical ingredient

AUC

Area under curve

BSA

Bovine serum albumin

CD

Circular dichroism

DSC

Differential scanning calorimetry

FCL

Freeze-concentrated liquid

FTIR

Fourier transform infrared spectroscopy

HPSEC

High performance size exclusion chromatography

IR

Infrared

LO

Light obscuration

XRD

Powder x-ray diffractometry

Notes

ACKNOWLEDGMENTS AND DISCLOSURES

This research was funded by an NSF grant (CBET-1335936) to A.A. Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from NSF through the MRSEC program.

Supplementary material

11095_2016_2078_MOESM1_ESM.docx (145 kb)
Figure S1 (DOCX 144 kb)
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Figure S2 (DOCX 137 kb)
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Figure S3 (DOCX 126 kb)
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Figure S4 (DOCX 139 kb)
11095_2016_2078_MOESM5_ESM.docx (176 kb)
Figure S5 (DOCX 176 kb)
11095_2016_2078_MOESM6_ESM.docx (19 kb)
Table S1 (DOCX 19 kb)

References

  1. 1.
    Chatterjee K, Shalaev EY, Suryanarayanan R. Partially crystalline systems in lyophilization: II. Withstanding collapse at high primary drying temperatures and impact on protein activity recovery. J Pharm Sci. 2005;94(4):809–20.PubMedCrossRefGoogle Scholar
  2. 2.
    Chatterjee K, Shalaev EY, Suryanarayanan R. Partially crystalline systems in lyophilization: I. Use of ternary state diagrams to determine extent of crystallization of bulking agent. J Pharm Sci. 2005;94(4):798–808.PubMedCrossRefGoogle Scholar
  3. 3.
    K-i I, Yoshioka S, Terao T. Decreased protein-stabilizing effects of cryoprotectants due to crystallization. Pharm Res. 1993;10(8):1232–7.CrossRefGoogle Scholar
  4. 4.
    Ken-ichi I, Sumie Y, Yasushi T. The effects of additives on the stability of freeze-dried β-galactosidase stored at elevated temperature. Int J Pharm. 1991;71(1):137–46.CrossRefGoogle Scholar
  5. 5.
    Johnson RE, Kirchhoff CF, Gaud HT. Mannitol–sucrose mixtures—versatile formulations for protein lyophilization. J Pharm Sci. 2002;91(4):914–22.PubMedCrossRefGoogle Scholar
  6. 6.
    Wang DQ, Hey JM, Nail SL. Effect of collapse on the stability of freeze‐dried recombinant factor VIII and α‐amylase. J Pharm Sci. 2004;93(5):1253–63.PubMedCrossRefGoogle Scholar
  7. 7.
    Crowe JH, Carpenter JF, Crowe LM. The role of vitrification in anhydrobiosis. Annu Rev Physiol. 1998;60(1):73–103.PubMedCrossRefGoogle Scholar
  8. 8.
    Crowe JH, Crowe LM, Oliver AE, Tsvetkova N, Wolkers W, Tablin F. The trehalose myth revisited: introduction to a symposium on stabilization of cells in the dry state. Cryobiology. 2001;43(2):89–105.PubMedCrossRefGoogle Scholar
  9. 9.
    Surana R, Pyne A, Suryanarayanan R. Effect of aging on the physical properties of amorphous trehalose. Pharm Res. 2004;21(5):867–74.PubMedCrossRefGoogle Scholar
  10. 10.
    Surana R, Pyne A, Suryanarayanan R. Effect of preparation method on physical properties of amorphous trehalose. Pharm Res. 2004;21(7):1167–76.PubMedCrossRefGoogle Scholar
  11. 11.
    Sundaramurthi P, Patapoff TW, Suryanarayanan R. Crystallization of trehalose in frozen solutions and its phase behavior during drying. Pharm Res. 2010;27(11):2374–83.PubMedCrossRefGoogle Scholar
  12. 12.
    Sundaramurthi P, Suryanarayanan R. Trehalose crystallization during freeze-drying: implications on lyoprotection. J Phys Chem Lett. 2009;1(2):510–4.CrossRefGoogle Scholar
  13. 13.
    Sundaramurthi P, Suryanarayanan R. Influence of crystallizing and non-crystallizing cosolutes on trehalose crystallization during freeze-drying. Pharm Res. 2010;27(11):2384–93.PubMedCrossRefGoogle Scholar
  14. 14.
    Carpenter JF, Pikal MJ, Chang BS, Randolph TW. Rational design of stable lyophilized protein formulations: some practical advice. Pharm Res. 1997;14(8):969–75.PubMedCrossRefGoogle Scholar
  15. 15.
    Randolph TW. Phase separation of excipients during lyophilization: effects on protein stability. J Pharm Sci. 1997;86(11):1198–203.PubMedCrossRefGoogle Scholar
  16. 16.
    Connolly BD, Le L, Patapoff TW, Cromwell ME, Moore JM, Lam P. Protein Aggregation in Frozen Trehalose Formulations: Effects of Composition, Cooling Rate, and Storage Temperature. J Pharm Sci. 2015;104(12):4170–84.PubMedCrossRefGoogle Scholar
  17. 17.
    Gómez G, Pikal MJ, Rodríguez-Hornedo N. Effect of initial buffer composition on pH changes during far-from-equilibrium freezing of sodium phosphate buffer solutions. Pharm Res. 2001;18(1):90–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Jena S, Suryanarayanan R, Aksan A. Mutual Influence of Mannitol and Trehalose on Crystallization Behavior in Frozen Solutions. Pharm Res. 2016;33(6):1413–25.PubMedCrossRefGoogle Scholar
  19. 19.
    Hawe A, Friess W. Physicohemical characterization of the freezing behavior of mannitol-human serum albumin formulations. AAPS PharmSciTech. 2006;7(4):E85–94.PubMedCentralCrossRefGoogle Scholar
  20. 20.
    Kim AI, Akers MJ, Nail SL. The physical state of mannitol after freeze‐drying: Effects of mannitol concentration, freezing rate, and a noncrystallizing cosolute. J Pharm Sci. 1998;87(8):931–5.PubMedCrossRefGoogle Scholar
  21. 21.
    Liao X, Krishnamurthy R, Suryanarayanan R. Influence of the active pharmaceutical ingredient concentration on the physical state of mannitol—implications in freeze-drying. Pharm Res. 2005;22(11):1978–85.PubMedCrossRefGoogle Scholar
  22. 22.
    Liao X, Krishnamurthy R, Suryanarayanan R. Influence of processing conditions on the physical state of mannitol—implications in freeze-drying. Pharm Res. 2007;24(2):370–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Telang C, Yu L, Suryanarayanan R. Effective inhibition of mannitol crystallization in frozen solutions by sodium chloride. Pharm Res. 2003;20(4):660–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Collins KD. Ions from the Hofmeister series and osmolytes: effects on proteins in solution and in the crystallization process. Methods. 2004;34(3):300–11.PubMedCrossRefGoogle Scholar
  25. 25.
    Rodríguez‐Hornedo N, Murphy D. Surfactant‐facilitated crystallization of dihydrate carbamazepine during dissolution of anhydrous polymorph. J Pharm Sci. 2004;93(2):449–60.PubMedCrossRefGoogle Scholar
  26. 26.
    Helgason T, Awad T, Kristbergsson K, McClements DJ, Weiss J. Effect of surfactant surface coverage on formation of solid lipid nanoparticles (SLN). J Colloid Interface Sci. 2009;334(1):75–81.PubMedCrossRefGoogle Scholar
  27. 27.
    Chang BS, Kendrick BS, Carpenter JF. Surface‐induced denaturation of proteins during freezing and its inhibition by surfactants. J Pharm Sci. 1996;85(12):1325–30.PubMedCrossRefGoogle Scholar
  28. 28.
    Kreilgaard L, Frokjaer S, Flink JM, Randolph TW, Carpenter JF. Effects of additives on the stability of Humicola lanuginosa lipase during freeze‐drying and storage in the dried solid. J Pharm Sci. 1999;88(3):281–90.PubMedCrossRefGoogle Scholar
  29. 29.
    Liu XQ, Sano Y. Effect of Na + and K+ ions on the initial crystallization process of lysozyme in the presence of D2O and H2O. J Protein Chem. 1998;17(5):479–84.PubMedCrossRefGoogle Scholar
  30. 30.
    Liu B, Garnett JA, Lee W-C, Lin J, Salgado P, Taylor J, et al. Promoting crystallisation of the Salmonella enteritidis fimbriae 14 pilin SefD using deuterium oxide. Biochem Biophys Res Commun. 2012;421(2):208–13.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Komatsu Y, Obuchi K, Iwahashi H, Kaul SC, Ishimura M, Fahy G, et al. Deutrium oxide, dimethylsulfoxide and heat shock confer protection against hydrostatic pressure damage in yeast. Biochem Biophys Res Commun. 1991;174(3):1141–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Edington BV, Whelan SA, Hightower LE. Inhibition of heat shock (stress) protein induction by deuterium oxide and glycerol: additional support for the abnormal protein hypothesis of induction. J Cell Physiol. 1989;139(2):219–28.PubMedCrossRefGoogle Scholar
  33. 33.
    Nicolajsen H, Hvidt A. Phase behavior of the system trehalose-NaCl-water. Cryobiology. 1994;31(2):199–205.CrossRefGoogle Scholar
  34. 34.
    Green JL, Angell CA. Phase relations and vitrification in saccharide-water solutions and the trehalose anomaly. J Phys Chem. 1989;93(8):2880–2.CrossRefGoogle Scholar
  35. 35.
    Miller DP, de Pablo JJ, Corti H. Thermophysical properties of trehalose and its concentrated aqueous solutions. Pharm Res. 1997;14(5):578–90.PubMedCrossRefGoogle Scholar
  36. 36.
    Her L-M, Nail SL. Measurement of glass transition temperatures of freeze-concentrated solutes by differential scanning calorimetry. Pharm Res. 1994;11(1):54–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Sreerama N, Venyaminov SY, Woody RW. Estimation of the number of α‐helical and β‐strand segments in proteins using circular dichroism spectroscopy. Protein Sci. 1999;8(2):370–80.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Toffel-Nadolny P. Infrared spectroscopic determinations of mannitol. Arch Kriminol. 1980;168(5–6):133–8.Google Scholar
  39. 39.
    Carpenter JF, Crowe JH. An infrared spectroscopic study of the interactions of carbohydrates with dried proteins. Biochemistry. 1989;28(9):3916–22.PubMedCrossRefGoogle Scholar
  40. 40.
    Belton P, Gil A. IR and Raman spectroscopic studies of the interaction of trehalose with hen egg white lysozyme. Biopolymers. 1994;34(7):957–61.PubMedCrossRefGoogle Scholar
  41. 41.
    Burger A, Henck JO, Hetz S, Rollinger JM, Weissnicht AA, Stoettner H. Energy/temperature diagram and compression behavior of the polymorphs of D‐mannitol. J Pharm Sci. 2000;89(4):457–68.PubMedCrossRefGoogle Scholar
  42. 42.
    Lin S-Y, Chien J-L. In vitro simulation of solid-solid dehydration, rehydration, and solidification of trehalose dihydrate using thermal and vibrational spectroscopic techniques. Pharm Res. 2003;20(12):1926–31.PubMedCrossRefGoogle Scholar
  43. 43.
    Pevsner A, Diem M. Infrared spectroscopic studies of major cellular components. Part I: the effect of hydration on the spectra of proteins. Appl Spectrosc. 2001;55(6):788–93.CrossRefGoogle Scholar
  44. 44.
    Wellner N, Belton PS, Tatham AS. Fourier transform IR spectroscopic study of hydration-induced structure changes in the solid state of ω-gliadins. Biochem J. 1996;319(3):741–7.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Gallagher W. FTIR analysis of protein structure. Course manual Chem. 2009;455.Google Scholar
  46. 46.
    Arrondo JLR, Goñi FM. Structure and dynamics of membrane proteins as studied by infrared spectroscopy. Prog Biophys Mol Biol. 1999;72(4):367–405.PubMedCrossRefGoogle Scholar
  47. 47.
    Jabs A. Determination of secondary structure in proteins by fourier transform infrared spectroscopy (FTIR). Biol Macromol. 2000.Google Scholar
  48. 48.
    Barth A. Infrared spectroscopy of proteins. Biochim Biophys Acta Bioenerg. 2007;1767(9):1073–101.CrossRefGoogle Scholar
  49. 49.
    Vogel HJ. Calcium-binding protein protocols: Springer Science & Business Media; 2004.Google Scholar
  50. 50.
    Uversky V, Longhi S. Instrumental analysis of intrinsically disordered proteins: assessing structure and conformation: John Wiley & Sons; 2011.Google Scholar
  51. 51.
    Data ICfD. Powder Diffraction File. Hexagonal ice, card # 00-042-1142; D-trehalose dihydrate, card # 00-029-1955; trehalose anhydrate, card # 00-003-0312; β-D-mannitol, card # 00-022-1797; δ-D-mannitol, card # 00-022-1794. In: Powder Diffraction File. Newtown Square; 2004.Google Scholar
  52. 52.
    Mahler HC, Friess W, Grauschopf U, Kiese S. Protein aggregation: pathways, induction factors and analysis. J Pharm Sci. 2009;98(9):2909–34.PubMedCrossRefGoogle Scholar
  53. 53.
    Narhi LO, Schmit J, Bechtold‐Peters K, Sharma D. Classification of protein aggregates. J Pharm Sci. 2012;101(2):493–8.PubMedCrossRefGoogle Scholar
  54. 54.
    Deluca P, Lachman L. Lyophilization of pharmaceuticals I. Effect of certain physical‐chemical properties. J Pharm Sci. 1965;54(4):617–24.PubMedCrossRefGoogle Scholar
  55. 55.
    Williams NA, Dean T. Vial breakage by frozen mannitol solutions: correlation with thermal characteristics and effect of stereoisomerism, additives, and vial configuration. PDA J Pharm Sci Technol. 1991;45(2):94–100.Google Scholar
  56. 56.
    Maa Y-F, Costantino HR, Nguyen P-A, Hsu CC. The effect of operating and formulation variables on the morphology of spray-dried protein particles. Pharm Dev Technol. 1997;2(3):213–23.PubMedCrossRefGoogle Scholar
  57. 57.
    Costantino HR, Andya JD, Nguyen PA, Dasovich N, Sweeney TD, Shire SJ, et al. Effect of mannitol crystallization on the stability and aerosol performance of a spray‐dried pharmaceutical protein, recombinant humanized anti‐IgE monoclonal antibody. J Pharm Sci. 1998;87(11):1406–11.PubMedCrossRefGoogle Scholar
  58. 58.
    Twomey A, Less R, Kurata K, Takamatsu H, Aksan A. In situ spectroscopic quantification of protein–ice interactions. J Phys Chem B. 2013;117(26):7889–97.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Miyazaki T, Yoshioka S, Aso Y, Kojima S. Ability of polyvinylpyrrolidone and polyacrylic acid to inhibit the crystallization of amorphous acetaminophen. J Pharm Sci. 2004;93(11):2710–7.PubMedCrossRefGoogle Scholar
  60. 60.
    Johari GP. Intrinsic mobility of molecular glasses. J Chem Phys. 1973;58(4):1766–70.CrossRefGoogle Scholar
  61. 61.
    Roudaut G, Simatos D, Champion D, Contreras-Lopez E, Le Meste M. Molecular mobility around the glass transition temperature: a mini review. Innovative Food Sci Emerg Technol. 2004;5(2):127–34.CrossRefGoogle Scholar
  62. 62.
    Dugua J, Simon B. Crystallization of sodium perborate from aqueous solutions: II. Growth kinetics of different faces in pure solution and in the presence of a surfactant. J Cryst Growth. 1978;44(3):280–6.CrossRefGoogle Scholar
  63. 63.
    Garti N, Zour H. The effect of surfactants on the crystallization and polymorphic transformation of glutamic acid. J Cryst Growth. 1997;172(3):486–98.CrossRefGoogle Scholar
  64. 64.
    Ffiredi-Milhoferlźr H, Tunikl L, Filipovic-VincekovicZ N, Skrticz D, Babic-lvancic V, Ganil N. Induction of crystallization of calcium oxalate dihydrate in micellar solutions of anionic surfactants. Scanning Microsc. 1995;9(4):1061–70.Google Scholar
  65. 65.
    Patist A, Bhagwat S, Penfield K, Aikens P, Shah D. On the measurement of critical micelle concentrations of pure and technical-grade nonionic surfactants. J Surfactant Deterg. 2000;3(1):53–8.CrossRefGoogle Scholar
  66. 66.
    Mohajeri E, Noudeh GD. Effect of temperature on the critical micelle concentration and micellization thermodynamic of nonionic surfactants: polyoxyethylene sorbitan fatty acid esters. J Chem. 2012;9(4):2268–74.Google Scholar
  67. 67.
    Rodríguez‐hornedo N, Murphy D. Significance of controlling crystallization mechanisms and kinetics in pharmaceutical systems. J Pharm Sci. 1999;88(7):651–60.PubMedCrossRefGoogle Scholar
  68. 68.
    Reddy K, Salvati L, Dutta PK, Abel PB, Suh KI, Ansari RR. Reverse micelle based growth of zincophosphate sodalite: Examination of crystal growth. J Phys Chem. 1996;100(23):9870–80.CrossRefGoogle Scholar
  69. 69.
    Luhtala S. Effect of sodium lauryl sulphate and polysorbate 80 on crystal growth and aqueous solubility of carbamazepine. Acta Pharm Nordica. 1992;4(2):85–90.Google Scholar
  70. 70.
    Weissbuch I, Addadi L, Leiserowitz L, Lahav M. Total asymmetric transformations at interfaces with centrosymmetric crystals: role of hydrophobic and kinetic effects in the crystallization of the system glycine/. alpha.-amino acids. J Am Chem Soc. 1988;110(2):561–7.CrossRefGoogle Scholar
  71. 71.
    Bujan M, Sikiric M, Filipovic-Vincekovic N, Vdovic N, Garti N, Füredi-Milhofer H. Effect of anionic surfactants on crystal growth of calcium hydrogen phosphate dihydrate. Langmuir. 2001;17(21):6461–70.CrossRefGoogle Scholar
  72. 72.
    Andronis V, Yoshioka M, Zografi G. Effects of sorbed water on the crystallization of indomethacin from the amorphous state. J Pharm Sci. 1997;86(3):346–51.PubMedCrossRefGoogle Scholar
  73. 73.
    Zhou R, Schlam RF, Yin S, Gandhi RB, Adams ML. Scale considerations for selection of saccharide excipients for liquid formulations. J Pharm Sci. 2011;100(4):1605–6.PubMedCrossRefGoogle Scholar
  74. 74.
    Zipp G, Rodriguez-Hornedo N. Growth mechanism and morphology of phenytoin and their relationship with crystallographic structure. J Phys D Appl Phys. 1993;26(8B):B48.CrossRefGoogle Scholar
  75. 75.
    Lazar KL, Patapoff TW, Sharma VK. Cold denaturation of monoclonal antibodies. In: MAbs: Taylor & Francis; 2010, 42–52.Google Scholar
  76. 76.
    Wolkers WF, Balasubramanian SK, Ongstad EL, Zec HC, Bischof JC. Effects of freezing on membranes and proteins in LNCaP prostate tumor cells. Biochim Biophys Acta Biomembr. 2007;1768(3):728–36.CrossRefGoogle Scholar
  77. 77.
    Koseki T, Kitabatake N, Doi E. Freezing denaturation of ovalbumin at acid pH. J Biochem. 1990;107(3):389–94.PubMedGoogle Scholar
  78. 78.
    Chang LL, Pikal MJ. Mechanisms of protein stabilization in the solid state. J Pharm Sci. 2009;98(9):2886–908.PubMedCrossRefGoogle Scholar
  79. 79.
    Chang LL, Shepherd D, Sun J, Ouellette D, Grant KL, Tang XC, et al. Mechanism of protein stabilization by sugars during freeze‐drying and storage: Native structure preservation, specific interaction, and/or immobilization in a glassy matrix? J Pharm Sci. 2005;94(7):1427–44.PubMedCrossRefGoogle Scholar
  80. 80.
    Bhatnagar BS, Bogner RH, Pikal MJ. Protein stability during freezing: separation of stresses and mechanisms of protein stabilization. Pharm Dev Technol. 2007;12(5):505–23.PubMedCrossRefGoogle Scholar
  81. 81.
    Dong J, Hubel A, Bischof JC, Aksan A. Freezing-induced phase separation and spatial microheterogeneity in protein solutions. J Phys Chem B. 2009;113(30):10081–7.PubMedCrossRefGoogle Scholar
  82. 82.
    Marini I, Moschini R, Del Corso A, Mura U. Chaperone-like features of bovine serum albumin: a comparison with α-crystallin. Cell Mol Life Sci. 2005;62(24):3092–9.PubMedCrossRefGoogle Scholar
  83. 83.
    Ellis J. Proteins as molecular chaperones. Nature. 1987;328(6129):378.PubMedCrossRefGoogle Scholar
  84. 84.
    Arakawa T, Prestrelski SJ, Kenney WC, Carpenter JF. Factors affecting short-term and long-term stabilities of proteins. Adv Drug Deliv Rev. 2001;46(1):307–26.PubMedCrossRefGoogle Scholar
  85. 85.
    Cao E, Chen Y, Cui Z, Foster PR. Effect of freezing and thawing rates on denaturation of proteins in aqueous solutions. Biotechnol Bioeng. 2003;82(6):684–90.PubMedCrossRefGoogle Scholar
  86. 86.
    Pikal-Cleland KA, Rodríguez-Hornedo N, Amidon GL, Carpenter JF. Protein denaturation during freezing and thawing in phosphate buffer systems: monomeric and tetrameric β-galactosidase. Arch Biochem Biophys. 2000;384(2):398–406.PubMedCrossRefGoogle Scholar
  87. 87.
    Zakharov B, Fisyuk A, Fitch A, Watier Y, Kostyuchenko A, Varshney D, Sztucki M, Boldyreva E, Shalaev E. Ice Recrystallization in a Solution of a Cryoprotector and Its Inhibition by a Protein: Synchrotron X-Ray Diffraction Study. J Pharm Sci. 2016.Google Scholar
  88. 88.
    Cleland JL, Lam X, Kendrick B, Yang J, Yang T, Overcashier D, et al. A specific molar ratio of stabilizer to protein is required for storage stability of a lyophilized monoclonal antibody. J Pharm Sci. 2001;90(3):310–21.PubMedCrossRefGoogle Scholar
  89. 89.
    Andya JD, Maa Y-F, Costantino HR, Nguyen P-A, Dasovich N, Sweeney TD, et al. The effect of formulation excipients on protein stability and aerosol performance of spray-dried powders of a recombinant humanized anti-IgE monoclonal antibody1. Pharm Res. 1999;16(3):350–8.PubMedCrossRefGoogle Scholar
  90. 90.
    Jia Y, Narayanan J, Liu X-Y, Liu Y. Investigation on the mechanism of crystallization of soluble protein in the presence of nonionic surfactant. Biophys J. 2005;89(6):4245–51.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Velev O, Pan Y, Kaler E, Lenhoff A. Molecular effects of anionic surfactants on lysozyme precipitation and crystallization. Cryst Growth Des. 2005;5(1):351–9.CrossRefGoogle Scholar
  92. 92.
    Berger BW, Gendron CM, Lenhoff AM, Kaler EW. Effects of additives on surfactant phase behavior relevant to bacteriorhodopsin crystallization. Protein Sci. 2006;15(12):2682–96.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Matsuo K, Sakurada Y, Yonehara R, Kataoka M, Gekko K. Secondary-structure analysis of denatured proteins by vacuum-ultraviolet circular dichroism spectroscopy. Biophys J. 2007;92(11):4088–96.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Manning MC, Illangasekare M, Woody RW. Circular dichroism studies of distorted α-helices, twisted β-sheets, and β-turns. Biophys Chem. 1988;31(1–2):77–86.PubMedCrossRefGoogle Scholar
  95. 95.
    Kelly SM, Price NC. The use of circular dichroism in the investigation of protein structure and function. Curr Protein Pept Sci. 2000;1(4):349–84.PubMedCrossRefGoogle Scholar
  96. 96.
    Greenfield NJ. Using circular dichroism spectra to estimate protein secondary structure. Nat Protoc. 2006;1(6):2876–90.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Kong J, Yu S. Fourier transform infrared spectroscopic analysis of protein secondary structures. Acta Biochim Biophys Sin. 2007;39(8):549–59.PubMedCrossRefGoogle Scholar
  98. 98.
    Vigano C, Manciu L, Buyse F, Goormaghtigh E, Ruysschaert JM. Attenuated total reflection IR spectroscopy as a tool to investigate the structure, orientation and tertiary structure changes in peptides and membrane proteins. Pept Sci. 2000;55(5):373–80.CrossRefGoogle Scholar
  99. 99.
    Maglott EJ, Goodwin JT, Glick GD. Probing the structure of an RNA tertiary unfolding transition state. J Am Chem Soc. 1999;121(32):7461–2.CrossRefGoogle Scholar
  100. 100.
    Galka JJ, Baturin SJ, Manley DM, Kehler AJ, O’neil JD. Stability of the Glycerol Facilitator in Detergent Solutions†. Biochemistry. 2008;47(11):3513–24.PubMedCrossRefGoogle Scholar
  101. 101.
    Jordan GM, Yoshika S, Terao T. The aggregation of bovine serum albumin in solution and in the solid state. J Pharm Pharmacol. 1994;46(3):182–5.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Biostabilization Laboratory, Department of Mechanical EngineeringUniversity of MinnesotaMinneapolisUSA
  2. 2.Department of Pharmacy, Pharmaceutical Technology and BiopharmaceuticsLudwig-Maximilians-Universität MünchenMunichGermany
  3. 3.Department of PharmaceuticsUniversity of MinnesotaMinneapolisUSA
  4. 4.The BioTechnology InstituteUniversity of MinnesotaMinneapolisUSA

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