Mid and Near Infrared Spectroscopy

  • Gabriele ReichEmail author
Part of the Advances in Delivery Science and Technology book series (ADST)


Vibrational spectroscopy in the mid (MIR) and near infrared (NIR) range provides structural information on virtually any organic compound and thus presents many interesting perspectives in both qualitative and quantitative analysis. These two techniques are powerful analytical tools for the identification and molecular characterization of pharmaceutical raw materials, intermediates and final dosage forms. NIR spectroscopy being fast, noninvasive, multiparametric, robust and easy to interface with a process, perfectly matches the measurement system requirements within the process analytical technology (PAT) framework. This chapter focuses on modern pharmaceutical MIR and NIR applications and covers (1) basic principles of both techniques including recent advances in instrumentation, sampling and data processing, (2) characterization of solid drug molecules and excipients, (3) nondestructive analysis of solid oral dosage forms, (4) secondary structural analysis of protein therapeutics, and (5) real-time process monitoring and control in drug substance and drug product manufacture. Strategies of MIR and NIR signal processing and multivariate NIR method implementation are highlighted and practical challenges of specific applications discussed. Finally, theoretical and practical aspects of NIR in vivo applications are briefly reviewed. Overall, the analytical versatility of infrared spectroscopy to be applied in various fields of pharmaceutical development, production and quality control is demonstrated and potential benefits and limitations of the distinct wavelength regions are scrutinized.


Noninvasive analysis Spectral sampling Signal processing Multivariate calibration Method validation Solid-state analysis Timely measurements Process understanding Process control 


  1. Aaltonen J, Rantanen J, Siiriä S et al (2003) Polymorph screening using near-infrared spectroscopy. Anal Chem 75:5267–5273CrossRefGoogle Scholar
  2. Aaltonen J, Strachan CJ, Pöllänen K et al (2007a) Hyphenated spectroscopy as a polymorph screening tool. J Pharm Biomed Anal 44:477–483PubMedCrossRefGoogle Scholar
  3. Aaltonen J, Kogermann K, Strachan JC et al (2007b) In-line monitoring of solid-state transitions during fluidisation. Chem Eng Sci 62:408–415CrossRefGoogle Scholar
  4. Abdul-Fattah AM, Truong-Le V, Yee L et al (2007) Drying-induced variations in physico-chemical properties of amorphous pharmaceuticals and their impact on stability I: stability of a monoclonal antibody. J Pharm Sci 96:1983–2008PubMedCrossRefGoogle Scholar
  5. Abrahamson C, Johannson J, Sparen A et al (2003) Comparison of different variable selection methods conducted on NIR transmission measurements on intact tablets. Chemom Intell Lab Syst 69:3–12CrossRefGoogle Scholar
  6. Acevedo D, Muliadi A, Giridhar A et al (2012) Evaluation of three approaches for real-time monitoring of roller compaction with near-infrared spectroscopy. AAPS PharmSciTech 13:1005–1012PubMedPubMedCentralCrossRefGoogle Scholar
  7. Aigner Z, Berkesi O, Farkas G et al (2012) DSC, X-ray and FTIR studies of a gemfibrozil/dimethyl-beta-cyclodextrin inclusion complex produced by co-grinding. J Pharm Biomed Anal 57:62–67PubMedCrossRefGoogle Scholar
  8. Alatalo HM, Hatakka H, Louhi-Kultanen M et al (2010) Closed-loop control of reactive crystallization. Part I: Supersaturation-controlled crystallization of L-glutamic acid. Chem Eng Technol 33:743–750CrossRefGoogle Scholar
  9. Alcalà M, Ropero J, Váquez R et al (2009) Deconvolution of chemical and physical information from intact tablets NIR spectra: two- and three-way multivariate calibration strategies for drug quantification. J Pharm Sci 98:2747–2758PubMedCrossRefGoogle Scholar
  10. Alcala M, Blanco M, Bautista M et al (2010) On-line monitoring of a granulation process by NIR spectroscopy. J Pharm Sci 99:336–345PubMedCrossRefGoogle Scholar
  11. Alcala M, Blanco M, Moyano D et al (2013) Qualitative and quantitative pharmaceutical analysis with a novel hand-held miniature near infrared spectrometer. J Near Infrared Spectrosc 21:445–457CrossRefGoogle Scholar
  12. Al-Hussein A, Giesseler H (2013) Investigation of histidine stabilizing effects on LDH during freeze-drying. J Pharm Sci 102:813–826PubMedCrossRefGoogle Scholar
  13. AllesØ M, Velaga S, Alhalaweh A, Cornett C et al (2008) Near-infrared spectroscopy for cocrystall screening. A comparative study with Raman spectroscopy. Anal Chem 80:7755–7764PubMedCrossRefGoogle Scholar
  14. Almeida A, Saerens L, De Beer T et al (2012) Upscaling and in-line process monitoring via spectroscopic techniques of ethylene vinyl acetate hot-melt extruded formulations. Int J Pharm 439:223–229PubMedCrossRefGoogle Scholar
  15. Alshahrani SM, Lu W, Park JB et al (2015) Stability-enhanced hot-melt extruded amorphous solid dispersions via combinations of Soluplus and HPMCAS-HF. AAPS PharmSciTech. doi: 10.1208/s12249-014-0269-6 PubMedPubMedCentralGoogle Scholar
  16. Alvarenga L, Ferreira D, Altekruse D et al (2008) Tablet identification using near-infrared spectroscopy (NIRS) for pharmaceutical quality control. J Pharm Biomed Anal 48:62–69PubMedCrossRefGoogle Scholar
  17. Andanson JM, Jutz F, Baiker A (2010) Simple in situ monitoring of a complex catalytic reaction network at high pressure by attenuated total reflection Fourier transform infrared spectroscopy. Appl Spectrosc 64:286–292PubMedCrossRefGoogle Scholar
  18. Anderson CA, Drennen JK, Ciurczak EW (2008) Pharmaceutical applications of near-infrared spectroscopy. In: Burns DA, Ciurczak EW (eds) Handbook of near infrared spectroscopy, 3rd edn. CRC Press, Boca RatonGoogle Scholar
  19. Andya JD, Hsu CC, Shire SJ (2003) Mechanisms of aggregate formation and carbohydrate excipient stabilization of lyophilized humanized monoclonal antibody formulations. AAPS PharmSci 5:Article 10Google Scholar
  20. Austin J, Gupta A, McDonell R et al (2013) The use of near-infrared and microwave resonance sensing to monitor a continuous roller compaction process. J Pharm Sci 102:1895–1904PubMedCrossRefGoogle Scholar
  21. Bai SJ, Rani M, Suryanarayanan R et al (2004) Quantification of glycine crystallinity by near-infrared (NIR) spectroscopy. J Pharm Sci 93:2439–2447PubMedCrossRefGoogle Scholar
  22. Bai S, Nayar R, Carpenter JF, Manning MC (2005) Noninvasive determination of protein conformation in the solid state using near infrared (NIR) spectroscopy. J Pharm Sci 94:2030–2038PubMedCrossRefGoogle Scholar
  23. Baiz CR, Peng CS, Reppert ME et al (2012a) Coherent two-dimensional infrared spectroscopy: quantitative analysis of protein secondary structure in solution. Analyst 137:1793–1799PubMedCrossRefGoogle Scholar
  24. Baiz C, Reppert M, Tokmakoff A (2012b) Amide I two-dimensional infrared spectroscopy: methods for visualizing the vibrational structure of large proteins. J Phys Chem A 117:5955–5961PubMedCrossRefGoogle Scholar
  25. Bakri B, Weimer M, Hauck G, Reich G (2010) Implementation of NIR blend monitoring in early development: evaluation of calibration design and spectrometer configuration. Poster presented at AAPS annual meeting and exposition, New Orleans 2010Google Scholar
  26. Barajas MJ, Cassiani AR, Vargas W et al (2007) Near-infrared spectroscopic method for real-time monitoring of pharmaceutical powders during voiding. Appl Spectrosc 61:490–496PubMedCrossRefGoogle Scholar
  27. Barrett M, McNamara M, Hao HX et al (2010) Supersaturation tracking for the development, optimization and control of crystallization processes. Chem Eng Res Des 88:1108–1119CrossRefGoogle Scholar
  28. Barth A (2007) Infrared spectroscopy of proteins. Biochim Biophys Acta 1767:1073–1101PubMedCrossRefGoogle Scholar
  29. Barth A, Zscherp C (2002) What vibrations tell us about proteins. Q Rev Biophys 35:369–430PubMedCrossRefGoogle Scholar
  30. Basavoju S, Boström D, Velaga SP (2008) Indomethacin-saccharin cocrystal: design, synthesis and preliminary pharmaceutical characterization. Pharm Res 25:530–541PubMedCrossRefGoogle Scholar
  31. Benedetti C, Abatzoglou N, Simard JS et al (2007) Cohesive, multicomponent, dense powder flow characterization by NIR. Int J Pharm 336:292–301PubMedCrossRefGoogle Scholar
  32. Bertacche V, Pini E, Stradi R et al (2006) Quantitative determination of amorphous cyclosporine in crystalline cyclosporine samples by Fourier transform infrared spectroscopy. J Pharm Sci 95:159–166PubMedCrossRefGoogle Scholar
  33. Blanco M, Alcala M (2006) Content uniformity and tablet hardness testing of intact pharmaceutical tablets by near infrared spectroscopy: a contribution to process analytical technologies. Anal Chim Acta 557:353–359CrossRefGoogle Scholar
  34. Blanco M, Peguero A (2010) Influence of physical factors on the accuracy of calibration models for NIR spectroscopy. J Pharm Biomed Anal 52:59–65PubMedCrossRefGoogle Scholar
  35. Blanco M, Romero MA (2001) Near-infrared libraries in the pharmaceutical industry: a solution for identity confirmation. Analyst 26:2212–2217CrossRefGoogle Scholar
  36. Blanco M, Villar A (2003) Development and validation of a method for the polymorphic analysis of pharmaceutical preparations using near infrared spectroscopy. J Pharm Sci 92:823–830PubMedCrossRefGoogle Scholar
  37. Blanco M, Coello J, Iturriaga H et al (1998) Near-infrared spectroscopy in the pharmaceutical industry. Analyst 123:135R–150RPubMedCrossRefGoogle Scholar
  38. Blanco M, Coello J, Montoliu I, Romero MA (2001) Orthogonal signal correction in near-infrared calibration. Anal Chim Acta 434:125–132CrossRefGoogle Scholar
  39. Blanco M, Valdés D, Llorente I et al (2005) Application of NIR spectroscopy in polymorphic analysis study of pseudo-polymorphs stability. J Pharm Sci 94:1336–1342PubMedCrossRefGoogle Scholar
  40. Blanco M, Castillo M, Peinado A et al (2006a) Application of multivariate curve resolution to chemical process control of an esterification reaction monitored by near-infrared spectroscopy. Appl Spectrosc 60:641–647PubMedCrossRefGoogle Scholar
  41. Blanco M, Alcala M, González JM et al (2006b) A process analytical technology approach based on near infrared spectroscopy: tablet hardness, content uniformity, and dissolution test measurements of intact tablets. J Pharm Sci 95:2137–2144PubMedCrossRefGoogle Scholar
  42. Blanco M, Alcala M, González JM et al (2006c) Determination of dissolution profiles in intact pharmaceutical tablets by NIR spectroscopy. Process Anal Technol 3:25–28Google Scholar
  43. Blanco M, Castillo M, Beneyto R (2007) Study of reaction processes by in-line near-infrared spectroscopy in combination with multivariate curve resolution: esterification of myristic acid with isopropanol. Talanta 72:519–525PubMedCrossRefGoogle Scholar
  44. Blanco M, Cueva-Mestanza R, Peguero A (2011) NIR analysis of pharmaceutical samples without reference data: Improving the calibration. Talanta 85:2218–2225PubMedCrossRefGoogle Scholar
  45. Blum MM, John H (2012) Historical perspective and modern applications of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). Drug Test Anal 4:298–302PubMedCrossRefGoogle Scholar
  46. Bodén I, Nyström J, Lundskog B et al (2013) Non-invasive identification of melanoma with near-infrared and skin impedance spectroscopy. Skin Res Technol 19:e473–e478PubMedCrossRefGoogle Scholar
  47. Bogomolov A, Engler M, Melichar M et al (2010) In-line analysis of a fluid bed pellet coating process using a combination of near infrared and Raman spectroscopy. J Chemom 24:544–557CrossRefGoogle Scholar
  48. Boiret M, Meunier L, Ginot YM (2011) Tablet potency of tianeptine in coated tablets by near infrared spectroscopy: model optimization, calibration transfer and confidence intervals. J Pharm Biomed Anal 54:510–516PubMedCrossRefGoogle Scholar
  49. Boulet-Audet M, Byrne B, Kazarian SG (2014) High-throughput thermal stability analysis of a monoclonal antibody by attenuated total reflection FT-IR spectroscopic imaging. Anal Chem 86:9786–9793PubMedPubMedCentralCrossRefGoogle Scholar
  50. Bouveresse E, Campbell B (2008) Transfer of multivariate calibration models based on near-infrared spectroscopy. In: Burns DA, Ciurczak EW (eds) Handbook of near-infrared analysis, 3rd edn. CRC Press, Boca RatonGoogle Scholar
  51. Braga JWB, Poppi RJ (2004) Figures of merit for the determination of the polymorphic purity of carbamazepine by infrared spectroscopy and multivariate calibration. J Pharm Sci 93:2124–2134PubMedCrossRefGoogle Scholar
  52. Brittain HG (2009) Vibrational spectroscopic studies of cocrystals and salts. 1. The benzamide-benzoic acid system. Cryst Growth Des 9:2492–2499CrossRefGoogle Scholar
  53. Brülls M, Folestad S, Sparen A et al (2003) In-situ near-infrared spectroscopy monitoring in pharmaceutical industry. Pharm Res 20:494–499PubMedCrossRefGoogle Scholar
  54. Brülls M, Folestad S, Sparèn A et al (2007) Applying spectral peak area analysis in near-infrared spectroscopy moisture assays. J Pharm Biomed Anal 44:127–136PubMedCrossRefGoogle Scholar
  55. Bugay DE (2001) Characterization of the solid state: spectroscopic techniques. Adv Drug Deliv Rev 48:43–65PubMedCrossRefGoogle Scholar
  56. Burger T, Fricke J, Kuhn J (1998) NIR radiative transfer investigations to characterize pharmaceutical powders and their mixtures. J Near Infrared Spectrosc 6:33–40CrossRefGoogle Scholar
  57. Burggrave A, Monteyne T, Vervaet C et al (2013) Process analytical tools for monitoring, understanding, and control of pharmaceutical fluidized bed granulation: a review. Eur J Pharm Biopharm 83:2–15CrossRefGoogle Scholar
  58. Byler DM, Susi H (1986) Examination of the secondary structure of proteins by deconvolved FTIR spectra. Biopolymers 25:469–487PubMedCrossRefGoogle Scholar
  59. Cao W, Mao C, Chen W et al (2006) Differentiation and quantitative determination of surface and hydrate water in lyophilized mannitol using NIR spectroscopy. J Pharm Sci 95:2077–2086PubMedCrossRefGoogle Scholar
  60. Carpenter JF, Prestrelski SJ, Dong A (1998) Application of infrared spectroscopy to development of stable lyophilized protein formulations. Eur J Pharm Biopharm 45:231–238Google Scholar
  61. Carrasquillo KG, Constantino HR, Cordero RA et al (1999) On the structural preservation of recombinant human growth hormone in a dried film of a synthetic biodegradable polymer. J Pharm Sci 88: 166–173Google Scholar
  62. Cerasoli E, Ravi J, Garfagnini T et al (2014) Temperature denaturation and aggregation of a multi-domain protein (IgG1) investigated with an array of complementary biophysical methods. Anal Bioanal Chem 406:6577–6586PubMedCrossRefGoogle Scholar
  63. Cervera-Padrell AE, Nielsen JP, Pedersen MJ et al (2012) Monitoring and control of a continuous Grignard reaction for the synthesis of an active pharmaceutical ingredient intermediate using inline NIR spectroscopy. Org Process Res Dev 16:901–914CrossRefGoogle Scholar
  64. Chablani L, Taylor MK, Mehrotra A et al (2011) Inline real-time near-infrared granule moisture measurements of a continuous granulation-drying-milling process. AAPS PharmSciTech 12:1050–1055PubMedPubMedCentralCrossRefGoogle Scholar
  65. Chalmers JM, Griffiths PR (eds) (2001) Handbook of vibrational spectroscopy. Wiley, New YorkGoogle Scholar
  66. Chalus P, Walter S, Ulmschneider M (2007) Combined wavelet transform-artificial neural network use in tablet active content determination by near-infrared spectroscopy. Anal Chim Acta 591:219–224PubMedCrossRefGoogle Scholar
  67. Chan KLA, Fleming OS, Kazarian SG et al (2004) Polymorphism and devitrification of nifedipine under controlled humidity: a combined FT-Raman, IR and Raman microscopic investigation. J Raman Spectrosc 35:353–359CrossRefGoogle Scholar
  68. Chan KLA, Kazarian SG, Vassou D, Gionis V, Chryssikos GD (2007) In situ high-throughput study of drug polymorphism under controlled temperature and humidity using FT-IR spectroscopic imaging. Vib Spectrosc 43:221–226CrossRefGoogle Scholar
  69. Chanda A, Daly AM, Foley DA et al (2013) Industry perspectives on process analytical technology: tools and applications in API development. Org Process Res Dev 19:63–83CrossRefGoogle Scholar
  70. Chang L, Shephard D, Sun J et al (2005) Effect of sorbitol and residual moisture on the stability of lyophilized antibodies: implications for the mechanism of protein stabilization in the solid state. J Pharm Sci 94:1445–1455PubMedCrossRefGoogle Scholar
  71. Chavez PF, De Bleye C, Sacré PY et al (2013) Validation methodologies of near infrared spectroscopy methods in pharmaceutical applications. Eur Pharm Rev 18:3–6Google Scholar
  72. Chen Y, Thosar SS, Forbess RA et al (2001) Prediction of drug content and hardness of intact tablets using artificial neural network and near-infrared spectroscopy. Drug Dev Ind Pharm 27:623–631PubMedCrossRefGoogle Scholar
  73. Chieng N, Zujovic Z, Bowmaker G et al (2006) Effect of milling conditions on the solid-state conversion of ranitidine hydrochloride form I. Int J Pharm 327:36–44PubMedCrossRefGoogle Scholar
  74. Chieng N, Rades T, Saville D (2008) Formation and physical stability oft he amorphous phase of ranitidine hydrochloride polymorphs prepared by cryo-milling. Eur J Pharm Biopharm 68:771–780PubMedCrossRefGoogle Scholar
  75. Chieng N, Aaltonen J, Saville D et al (2009) Physical characterization and stability of amorphous indomethacin and ranitidine hydrochloride binary systems prepared by mechanical activation. Eur J Pharm Biopharm 71:47–54PubMedCrossRefGoogle Scholar
  76. Chieng N, Rades T, Aaltonen J (2011) An overview of recent studies on the analysis of pharmaceutical polymorphs. J Pharm Biomed Anal 55:618–644PubMedCrossRefGoogle Scholar
  77. Childs SL, Stahly GP, Park A (2007) The salt-cocrystal continuum: the influence of crystal structure on ionization state. Mol Pharm 4:323–338PubMedCrossRefGoogle Scholar
  78. Clegg IM, Daly AM, Donnelly C et al (2012) Application of mid-infrared spectroscopy to the development and transfer of a manufacturing process for an active pharmaceutical ingredient. Appl Spectrosc 66:574–579PubMedCrossRefGoogle Scholar
  79. Cleland JL, Lam X, Kendrick B et al (2001) A specific molar ration of stabilizer to protein is required for storage stability of a lyophilized monoclonal antibody. J Pharm Sci 90:310–321PubMedCrossRefGoogle Scholar
  80. Cogdill RP, Anderson CA (2005) Efficient spectroscopic calibration using net analyte signal and pure component projection methods. J Near Infrared Spectrosc 13:119–131CrossRefGoogle Scholar
  81. Cogdill RP, Anderson CA, Drennen JK (2005a) Process analytical technology case study, Part III: Calibration monitoring and transfer. AAPS PharmSciTech 6:E284–E297PubMedPubMedCentralCrossRefGoogle Scholar
  82. Cogdill RP, Anderson C, Chrisholm R et al (2005b) Process analytical technology case study, Part I: Feasibility studies for quantitative near-infrared method development. AAPS PharmSciTech 6:E262–E272PubMedPubMedCentralCrossRefGoogle Scholar
  83. Cogdill RP, Anderson C, Chrisholm R et al (2005c) Process analytical technology case study, Part II: Development and validation of quantitative near-infrared calibrations in support of a process analytical technology application for real-time release. AAPS PharmSciTech 6:E273–E283PubMedPubMedCentralCrossRefGoogle Scholar
  84. Colón YM, Florian MA, Acevedo D et al (2014) Near infrared method development for a continuous manufacturing blending process. J Pharm Innov 9:291–301CrossRefGoogle Scholar
  85. Constantino HR, Firouzabadian L, Wu C et al (2002) Protein spray freeze drying. 2. Effect of formulation variables on particle size and stability. J Pharm Sci 91:388–395CrossRefGoogle Scholar
  86. Cordone L, Cottone G, Giuffrida S et al (2005) Internal dynamics and protein-matrix coupling in trehalose-coated proteins. Biochim Biophys Acta 1749:252–281PubMedCrossRefGoogle Scholar
  87. Corredor CC, Bu D, Both D (2011) Comparison of near infrared and microwave resonance sensors for at-line moisture determination in powders and tablets. Anal Chim Acta 696:84–93PubMedCrossRefGoogle Scholar
  88. Cottone G, Giuffrida S, Cicotti G et al (2005) Molecular dynamics simulation of sucrose- and trehalose-coated carboxy-myoglobin. Proteins 59:291–302PubMedCrossRefGoogle Scholar
  89. Croker DM, Hennigan MC, Maher A et al (2012) A comparative study of the use of powder X-ray diffraction, Raman and near infrared spectroscopy for quantification of binary polymorphic mixtures of piracetam. J Pharm Biomed Anal 63:80–96PubMedCrossRefGoogle Scholar
  90. De Beer TRM, Vercruysse P et al (2009a) In-line and real-time process monitoring of a freeze drying process using Raman and NIR spectroscopy as complimentary process analytical technology (PAT) tools. J Pharm Sci 98:3430–3446PubMedCrossRefGoogle Scholar
  91. De Beer TRM, Wiggenhorn M et al (2009b) Importance of using complementary process analyzers for the process monitoring, analysis, and understanding of freeze drying. Anal Chem 81:7639–7649PubMedCrossRefGoogle Scholar
  92. De Beer T, Burggraeve A, Fonteyne M, Saerens L, Remon JP, Vervaet C (2011a) Near infrared and Raman spectroscopy for the in-process monitoring of pharmaceutical production processes. Int J Pharm 417:32–47PubMedCrossRefGoogle Scholar
  93. De Beer TR, Wiggenhorn M, Hawe A et al (2011b) Optimization of a pharmaceutical freeze-dried product and its process using an experimental design approach and innovative process analyzers. Talanta 83:1623–1633PubMedCrossRefGoogle Scholar
  94. De Bleye C, Chavez PF, Mantanus J et al (2012) Critical review of near-infrared spectroscopic methods validations in pharmaceutical applications. J Pharm Biomed Anal 69:125–132PubMedCrossRefGoogle Scholar
  95. Demirdöven N, Cheatum CM, Chung HS et al (2004) Two-dimensional infrared spectroscopy of antiparallel β-sheet secondary structure. J Am Chem Soc 126:7981–7990PubMedCrossRefGoogle Scholar
  96. Dong A, Huang P, Caughey WS (1990) Protein secondary structures in water from second-derivative amide I infrared spectra. Biochemistry 29:3303–3308PubMedCrossRefGoogle Scholar
  97. Donoso M, Ghaly ES (2005) Prediction of tablets disintegration times using near-infrared diffuse reflectance spectroscopy as a nondestructive method. Pharm Dev Technol 10:211–217PubMedCrossRefGoogle Scholar
  98. Du YP, Kasemsuran S, Jiang JH et al (2008) In vivo and in vitro near-infrared spectroscopic determination of blood glucose and other biomedical components with chemometrics. In: Burns DA, Ciurczak EW (eds) Handbook of near-infrared analysis, 3rd edn. CRC Press, Boca RatonGoogle Scholar
  99. Duffy D, Cremin N, Napier M et al (2012) In situ monitoring, control and optimization of a liquid-liquid phase separation crystallization. Chem Eng Sci 77:112–121CrossRefGoogle Scholar
  100. Duffy D, Barrett M, Glennon B (2013) Novel, calibration-free strategies for supersaturation control in antisolvent crystallization processes. Cryst Growth Des 13:3321–3332CrossRefGoogle Scholar
  101. Einfal T, Planinsek O, Hrovat K (2013) Methods of amophization and investigation of the amorphous state. Acta Pharm 63:305–334PubMedGoogle Scholar
  102. El-Hagrasy AS, Morris HR, D’Amico F et al (2001) Near-infrared spectroscopy and imaging for the monitoring of powder blend homogeneity. J Pharm Sci 90:1298–1307PubMedCrossRefGoogle Scholar
  103. El-Hagrasy AS, Delgado-Lopez M, Drennen JK (2006) A process analytical technology approach to near-infrared process control of pharmaceutical powder blending: Part II: qualitative near-infrared models for prediction of blend homogeneity. J Pharm Sci 95:407–421PubMedCrossRefGoogle Scholar
  104. EMA Guideline on the use of near infrared spectroscopy by the pharmaceutical industry and the data requirements for new submissions and variations, January (2014)Google Scholar
  105. Fabian H, Schultz C, Naumann D et al (1993) Secondary structure and temperature-induced unfolding and refolding of ribonuclease T1 in aqueous solution. A Fourier transform infrared spectroscopic study. J Mol Biol 232:967–981PubMedCrossRefGoogle Scholar
  106. Farrell JA, Higgins K, Kalivas JH (2012) Updating a near-infrared multivariate calibration model formed with lab-prepared pharmaceutical tablet types to new tablet types in fill production. J Pharm Biomed Anal 61:114–121PubMedCrossRefGoogle Scholar
  107. Feng T, Wang F, Pinal R et al (2008) Investigation of the variability of NIR in-line monitoring of roller compaction process by using fast fourier transform (FFT) analysis. AAPS PharmSciTech 9:419–424PubMedPubMedCentralCrossRefGoogle Scholar
  108. Figueiras A, Carvalho RA, Ribeiro L et al (2007) Solid-state characterization and dissolution profiles of the inclusion complexes of omeprazole with native and chemically modified beta-cyclodextrin. Eur J Pharm Biopharm 67:531–539PubMedCrossRefGoogle Scholar
  109. Findlay WP, Peck GR, Morris KR (2005) Determination of fluidized bed granulation end point using near-infrared spectroscopy and phenomenological analysis. J Pharm Sci 94:604–612PubMedCrossRefGoogle Scholar
  110. Fix I, Steffens KJ (2004) Quantifying low amorphous or crystalline amounts of alpha-lactose-monohydrate using X-ray powder diffraction, near-infrared spectroscopy, and differential scanning calorimetry. Drug Dev Ind Pharm 30:513–523PubMedCrossRefGoogle Scholar
  111. Fonteyne M, Soares S, Vercruysse J et al (2012) Prediction of quality attributes of continuously produced granules using complimentary PAT tools. Eur J Pharm Biopharm 82:429–436PubMedCrossRefGoogle Scholar
  112. Fonteyne M, Vercruysse J, Díaz DC et al (2013) Real-time assessment of critical quality attributes of a continuous granulation process. Pharm Dev Technol 18:85–97PubMedCrossRefGoogle Scholar
  113. Freitas MP, Sabadin A, Silva LM et al (2005) Prediction of drug dissolution profiles from tablets using NIR diffuse reflectance spectroscopy: a rapid and nondestructive method. J Pharm Biomed Anal 39:17–21PubMedCrossRefGoogle Scholar
  114. French DL, Arakawa T, Li T (2004) Fourier transform infrared spectroscopy investigation of protein conformation in spray-dried protein/trehalose powders. Biopolymers 73:524–531PubMedCrossRefGoogle Scholar
  115. Frickel H, Reich G (2000) NIR spectroscopy of film-coated tablets——fast and nondestructive evaluation of film coat uniformity and drug release kinetics. Proc Int Symp Contr Rel Bioact Mater 27:740–741Google Scholar
  116. Fu K, Griebenov K, Hsieh L et al (1999) FTIR characterization of the secondary structure of proteins encapsulated within PLGA microspheres. J Control Release 58:357–366PubMedCrossRefGoogle Scholar
  117. Ge Z, Thompson R, Cooper S et al (1995) Quantitative monitoring of an epoxidation process by Fourier transform infrared spectroscopy. Process Control Qual 7:3–12Google Scholar
  118. Gendre C, Boiret M, Genty M et al (2011a) Real-time predictions of drug release and end point detection of a coating operation by in-line near infrared measurements. Int J Pharm 421:237–243PubMedCrossRefGoogle Scholar
  119. Gendre C, Genty M, Boiret M et al (2011b) Development of a process analytical technology (PAT) for in-line monitoring of film thickness and mass of coating materials during a pan coating operation. Eur J Pharm Biopharm 43:244–250Google Scholar
  120. Giuffrida S, Cottone G, Cordone L (2004) Structure-dynamics coupling between protein and external matrix in sucrose-coated and trehalose-coated MbCO: an FTIR study. J Phys Chem 108:15415–15421CrossRefGoogle Scholar
  121. Gold TB, Buice RG Jr, Lodder RA et al (1997) Determination of extent of formaldehyde-induced crosslinking in hard gelatin capsules by near infrared spectroscopy. Pharm Res 14:1046–1050PubMedCrossRefGoogle Scholar
  122. Gold TB, Buice RG Jr, Lodder RA et al (1998) Detection of formaldehyde-induced crosslinking in soft elastic gelatin capsules using near-infrared spectrophotometry. Pharm Dev Technol 3:209–214PubMedCrossRefGoogle Scholar
  123. Gotter B, Faubel W, Neubert RH (2008) Optical methods for measurements of skin penetration. Skin Pharmacol Physiol 21:156–165PubMedCrossRefGoogle Scholar
  124. Green RL, Thurau G, Pixley NC et al (2005) In-line monitoring of moisture content in fluid bed dryers using near-IR spectroscopy with consideration of sampling effects on method accuracy. Anal Chem 77:4515–4522PubMedCrossRefGoogle Scholar
  125. Griffiths PR, De Haseth JA (2007) Fourier transform infrared spectrometry, 2nd edn. Wiley, New YorkCrossRefGoogle Scholar
  126. Grohganz H, Fonteyne M, Skibsted E et al (2009) Role of excipients in the quantification of water in lyophilized mixtures using NIR spectroscopy. J Pharm Biomed Anal 49:901–907PubMedCrossRefGoogle Scholar
  127. Grohganz H, Gildemyn D, Skibsted E et al (2010a) Towards a robust water content determination of freeze-dried samples by near-infrared spectroscopy. Anal Chim Acta 676:34–40PubMedCrossRefGoogle Scholar
  128. Grohganz H, Fonteyne M, Skibsted E et al (2010b) Classification of lyophilized mixtures using multivariate analysis of NIR spectra. Eur J Pharm Biopharm 74:406–412PubMedCrossRefGoogle Scholar
  129. Gupta A, Peck GE, Miller RW et al (2004) Nondestructive measurements of the compact strength and the particle-size distribution after milling of roller compacted powders by near-infrared spectroscopy. J Pharm Sci 93:1047–1053PubMedCrossRefGoogle Scholar
  130. Gupta A, Peck GE, Miller RW et al (2005a) Real-time near-infrared monitoring of content uniformity, moisture content, compact density, tensile strength, and Young’s modulus of roller compacted powder blends. J Pharm Sci 94:1589–1597PubMedCrossRefGoogle Scholar
  131. Gupta A, Peck GE, Miller RW et al (2005b) Influence of ambient moisture on the compaction behavior of microcrystalline cellulose powder undergoing uni-axial compression and roller compaction: a comparative study using near-infrared spectroscopy. J Pharm Sci 94:2301–2313PubMedCrossRefGoogle Scholar
  132. Hawe A, Kasper JC, Friess W et al (2009) Structural properties of monoclonal antibody aggregates induced by freeze-thawing and thermal stress. Eur J Pharm Sci 38:79–87PubMedCrossRefGoogle Scholar
  133. Heigl N, Koller DM, Glasser BJ et al (2013) Quantitative on-line vs. off-line NIR analysis of fluidized bed drying with consideration of the spectral background. Eur J Pharm Biopharm 85:1064–1074PubMedCrossRefGoogle Scholar
  134. Heinz A, Savolainen M, Rades T et al (2007) Quantifying ternary mixtures of different solid-state forms of indomethacin by Raman and near-infrared spectroscopy. Eur J Pharm Sci 32:182–192PubMedCrossRefGoogle Scholar
  135. Heinz A, Strachan CJ, Atassi F et al (2008) Characterizing an amorphous system exhibiting trace crystallinity: a case study with saquinavir. Cryst Growth Des 8:119–127CrossRefGoogle Scholar
  136. Heinz A, Strachan CJ, Gordon K et al (2009) Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopy. J Pharm Pharmacol 61:971–988PubMedCrossRefGoogle Scholar
  137. Heise HM (2002) Applications of near-infrared spectroscopy in medical sciences. In: Siesler HW, Ozaki Y, Kawara S, Heise HM (eds) Near-Infrared spectroscopy. Wiley, WeinheimGoogle Scholar
  138. Heise HM, Marbach R, Bittner A (1998) Clinical chemistry and near infrared spectroscopy: technology for non-invasive glucose monitoring. J Near Infrared Spectrosc 6:349–359CrossRefGoogle Scholar
  139. Heise HM, Küpper L, Butvina LN (2003) Novel infrared optical probes for process monitoring and analysis based on next-generation silver halide fibers. Anal Bioanal Chem 375:1116–1123PubMedGoogle Scholar
  140. Helmdach L, Feth MP, Minnich C et al (2013) Application of ATR-MIR spectroscopy in the pilot plant—scope and limitations using the example of paracetamol crystallizations. Chem Eng Proc 70:184–197CrossRefGoogle Scholar
  141. Hicks MB, Zhou GX, Lieberman DR et al (2003) In situ moisture determination of a cytotoxic compound during process optimization. J Pharm Sci 92:529–535PubMedCrossRefGoogle Scholar
  142. Higgins JP, Arrivo SM, Reed RA (2003) Approach to the determination of hydrate form conversions of drug compounds and solid dosage forms by near-infrared spectroscopy. J Pharm Sci 92:2303–2316PubMedCrossRefGoogle Scholar
  143. Ho L, Cuppok Y, Muschert S et al (2009) Effects of film coating thickness and drug layer uniformity on in vitro drug release from sustained-release coated pellets: a case study using terahertz pulsed imaging. Int J Pharm 382:151–159PubMedCrossRefGoogle Scholar
  144. Hsu CH, Ke WT, Lin SY (2010) Progressive steps of polymorphic transformation of gabapentin polymorphs studied by hot-stage FTIR microspectroscopy. J Pharm Pharm Sci 13:67–77PubMedCrossRefGoogle Scholar
  145. Hu S, Maslov K, Tsytsarov V et al (2009) Functional transcranial brain imaging by optical-resolution photoacoustic microscopy. J Biomed Opt 14:040503. doi: 10.1117/1.3194136 PubMedPubMedCentralCrossRefGoogle Scholar
  146. Hu Y, Erxleben A, Ryder AG et al (2010) Quantitative analysis of sulfathiazole polymorphs in ternary mixtures by attenuated total reflectance infrared, near-infrared and Raman spectroscopy. J Pharm Biopharm 53:412–420Google Scholar
  147. Hu Y, Macfhionnghaile P, Caron V et al (2013) Formation, physical stability, and quantification of process-induced disorder in cryomilled samples of a model polymorphic drug. J Pharm Sci 102:93–103PubMedCrossRefGoogle Scholar
  148. Huang J, Li Y, Wigent RJ et al (2011) Interplay of formulation and process methodology on the extent of nifedipine molecular dispersion in polymers. Int J Pharm 420:59–67PubMedCrossRefGoogle Scholar
  149. Igne B, de Juan A, Jaumot J et al (2014) Modeling strategies for pharmaceutical blend monitoring and end-point determination by near-infrared spectroscopy. Int J Pharm 473:219–231PubMedCrossRefGoogle Scholar
  150. International Conference on Harmonization (ICH) of Technical Requirements for registration of Pharmaceuticals for human Use, Topic Q2 (R1): Validation of analytical Procedures: Text and Methodology, Geneva (2005) Accessed 23 June 2015
  151. Izutzu KI, Fujimaki Y, Kuwabara A et al (2006) Near-infrared analysis of protein secondary structure in aqueous solutions and freeze-dried solids. J Pharm Sci 95:781–789CrossRefGoogle Scholar
  152. Järvinen K, Hoehe W, Järvinen M et al (2013) In-line monitoring of the drug content of powder mixtures and tablets by near-infrared spectroscopy during the continuous direct compression tabletting process. Eur J Pharm Sci 48:680–688PubMedCrossRefGoogle Scholar
  153. Jayasankar A, Somwangthanaroj A, Shao ZJ et al (2006) Cocrystal formation during cogrinding and storage is mediated by amorphous phase. Pharm Res 23:2381–2392PubMedCrossRefGoogle Scholar
  154. Jiang Y, Li C, Nguyen X, Muzammil S et al (2011) Qualification of FTIR spectroscopic method for protein secondary structural analysis. J Pharm Sci 100:4631–4641PubMedCrossRefGoogle Scholar
  155. Joergensen AC, Strachan CJ, Pöllänen KH, Koradia V, Tian F, Rantanen J (2009) An insight into water of crystallization during processing using vibrational spectroscopy. J Pharm Sci 98:3903–3932CrossRefGoogle Scholar
  156. Jorgensen L, Vermehren C, Bjerregaard S et al (2003) Secondary structure alterations in insulin and growth hormone water-in-oil emulsions. Int J Pharm 254:7–10PubMedCrossRefGoogle Scholar
  157. Jorgensen AC, Rantanen J, Luukkonen P et al (2004a) Visualization of a pharmaceutical unit operation; wet granulation. Anal Chem 76:5331–5338PubMedCrossRefGoogle Scholar
  158. Jorgensen AC, Luukkonen P, Rantanen J et al (2004b) Comparison of torque measurements and near-infrared spectroscopy in characterization of a wet granulation process. J Pharm Sci 93:2232–2243PubMedCrossRefGoogle Scholar
  159. Joubert MK, Luo Q, Nashed-Samuel Y et al (2011) Classification and characterization of therapeutic antibody aggregates. J Biol Chem 286:25118–25133PubMedPubMedCentralCrossRefGoogle Scholar
  160. Kadam SS, van der Windt E, Daudey PJ et al (2010) A comparative study of ATR-FTIR and FT-NIR spectroscopy for in-situ concentration monitoring during batch cooling crystallization processes. Cryst Growth Des 10:2629–2640CrossRefGoogle Scholar
  161. Kamat MS, Lodder RA, DeLuca PP (1989) Near-infrared spectroscopic determination of residual moisture in lyophilized sucrose through intact glass vials. Pharm Res 6:961–965PubMedCrossRefGoogle Scholar
  162. Kammerzell TJ, Middaugh CR (2007) Two-dimensional correlation spectroscopy reveals coupled immunoglobulin regions of differential flexibility that influence stability. Biochemistry 46:9762–9773CrossRefGoogle Scholar
  163. Kammerzell TJ, KIanai S, Liu JL et al (2009) Increasing IgG concentration modulates the conformational heterogeneity and bonding network that influence solution properties. J Phys Chem B 113:6109–6118CrossRefGoogle Scholar
  164. Karande AD, Heng PW, Liew CV (2010) In-line quantification of micronized drug and excipients in tablets by near-infrared (NIR) spectroscopy: real time monitoring of tbletting process. Int J Pharm 396:63–74PubMedCrossRefGoogle Scholar
  165. Karolewicz B, Górniak A, Owczarek A et al (2012) Solid dispersion in pharmaceutical technology. Part II. The methods of analysis of solid dispersions and examples of their application. Polim Med 42:97–107PubMedGoogle Scholar
  166. Kasemsumran S, Du YP, Maruo K et al (2006) Improvement of partial least squares models for in vitro and in vivo glucose quantifications by using near-infrared spectroscopy and searching combination moving window partial least squares. Chemom Intell Lab Syst 82:97–103CrossRefGoogle Scholar
  167. Kauppinen JK, Moffatt DJ, Matsch HH et al (1981) Fourier transforms in the computation of self-deconvoluted and first-order derivative spectra of overlapped band contours. Anal Chem 53:1454–1457CrossRefGoogle Scholar
  168. Kauppinen A, Toiviainen M et al (2013) In-line multipoint near-infrared spectroscopy for moisture content quantification during freeze-drying. Anal Chem 85:2377–2384PubMedCrossRefGoogle Scholar
  169. Kauppinen A, Toiviainen M et al (2014) Validation of a multipoint near-infrared spectroscopy method for in-line moisture content analysis during freeze-drying. J Pharm Biomed Anal 95:229–237PubMedCrossRefGoogle Scholar
  170. Kaushal AM, Chakraborti AK, Basal AK (2008) FTIR studies on differential intermolecular association in crystalline and amorphous states of structurally related non-steroidal anti-inflammatory drugs. Mol Pharm 5:937–945PubMedCrossRefGoogle Scholar
  171. Kee NCS, Tan RBH, Braatz RD (2009) Selective crystallization of the metastable α-form of L-glutamic acid using concentration feedback control. Cryst Growth Des 9:3044–3061CrossRefGoogle Scholar
  172. Kee NCS, Tan RBH, Braatz RD (2011) Semiautomated identification of the phase diagram for enantiotropic crystallizations using ATR-FTIR spectroscopy and laser backscattering. Ind Eng Chem Res 50:1488–1495CrossRefGoogle Scholar
  173. Keles H, Naylor A, Clegg F et al (2014) Studying the release of hGH from gamma-irradiated PLGA microparticles using ATR-FTIR imaging. Vib Spectrosc 71:76–84CrossRefGoogle Scholar
  174. Kelly AL, Gough T, Dhumal RS, Halsey SA et al (2012) Monitoring ibuprofen-nicotinamide cocrystal formation during solvent free continuous cocrystallization (SFCC) using near infrared spectroscopy as a PAT tool. Int J Pharm 426:15–20PubMedCrossRefGoogle Scholar
  175. Kendrick BS, Dong A, Allison D et al (1996) Quantification of the area of overlap between second-derivative amide I infrared spectra to determine the structural similarity of a protein in different states. J Pharm Sci 85:155–158PubMedCrossRefGoogle Scholar
  176. Kiefer J, Cöngevel MA, Roth D et al (2012) Attenuated total reflection infrared difference spectroscopy (ATR-IRDS) for quantitative reaction monitoring. Appl Spectrosc 66:685–688PubMedCrossRefGoogle Scholar
  177. Kirsch JD, Drennen JK (1995) Determination of film-coated tablet parameters by near-infrared spectroscopy. J Pharm Biomed Anal 13:1271–1281CrossRefGoogle Scholar
  178. Kirsch JD, Drennen JK (1999) Nondestructive tablet hardness testing ny near-infrared spectroscopy: a new and robust spectral best-fit algorithm. J Pharm Biomed Anal 19:351–369PubMedCrossRefGoogle Scholar
  179. Knop K, Kleinebudde P (2013) PAT-tools for process control in pharmaceutical film coating applications. Int J Pharm 457:527–536PubMedCrossRefGoogle Scholar
  180. Kogermann K, Aaltonen J, Strachan CJ et al (2007) Qualitative in situ analysis of multiple solid-state forms using spectroscopy and partial least squares discriminant modeling. J Pharm Sci 96:1802–1820PubMedCrossRefGoogle Scholar
  181. Kogermann K, Aaltonen J, Strachan CJ et al (2008) Establishing quantitative in-line analysis of multiple solid-state transformations during dehydration. J Pharm Sci 97:4983–4999PubMedCrossRefGoogle Scholar
  182. Kojima T, Yamauchi Y, Onoue S et al (2008) Evaluation of hydrate formation of a pharmaceutical solid by using diffuse reflectance infrared Fourier-transform spectroscopy. J Pharm Biomed Anal 46:788–791PubMedCrossRefGoogle Scholar
  183. Krier F, Mantanus J, Sacré PY et al (2013) PAT tools for the control of co-extrusion implants manufacturing process. Int J Pharm 458:15–24PubMedCrossRefGoogle Scholar
  184. Krzyzaniak JF, Williams GR, Ni N (2007) Identification of phase boundaries in anhydrate/hydrate systems. J Pharm Sci 96:1270–1281PubMedCrossRefGoogle Scholar
  185. Kumar A, Vercruysse J, Toiviainen M et al (2014) Mixing and transport during pharmaceutical twin-screw wet granulation: experimental anaylsis via chemical imaging. Eur J Pharm Biopharm 87:279–289PubMedCrossRefGoogle Scholar
  186. Lee MJ, Park CR, Kim AY et al (2010) Dynamic calibration for the in-line NIR monitoring of film thichness of pharmaceutical tablets processed in a fluid-bed coater. J Pharm Sci 99:325–335PubMedCrossRefGoogle Scholar
  187. Lee MJ, Seo DY, Lee HE et al (2011a) In line NIR quantification of film thickness on pharmaceutical pellets during a fluid bed coating process. Int J Pharm 403:66–72PubMedCrossRefGoogle Scholar
  188. Lee YY, Wu JX, Yang M et al (2011b) Particle size dependence of polymorphism in spray-dried mannitol. Eur J Pharm Sci 44:41–48PubMedCrossRefGoogle Scholar
  189. Lefèvre T, Arseneault K, Pézolet M (2004) Study of protein aggregation using two-dimensional correlation infrared spectroscopy and spectral simulations. Biopolymers 73:705–715PubMedCrossRefGoogle Scholar
  190. Leskinen JTT, Okkonen MAH, Toiviainen S et al (2010) Labscale fluidized bed granulator instrumented with non-invasive process monitoring devices. Chem Eng J 164:268–274CrossRefGoogle Scholar
  191. Li S (2010) Application of online reaction monitoring by Raman and infrared spectroscopy in early drug development: halogen-lithium exchange chemistry. Am Pharm Rev 13:62–67Google Scholar
  192. Li W, Worosila GD, Wang W et al (2005) Determination of polymorph conversion of an active pharmaceutical ingredient in wet granulation using NIR calibration models generated from the premix blends. J Pharm Sci 94:2800–2806PubMedCrossRefGoogle Scholar
  193. Li RF, Wang XZ, Ababe SB (2008) Monitoring batch cooling crystallization using NIR: development of calibration models using genetic algorithm and PLS. Part Part Syst Charact 25:314–327CrossRefGoogle Scholar
  194. Liao X, Gautam M, Grill A et al (2010) Effect of position isomerism on the formation and physicochemical properties of pharmaceutical co-crystals. J Pharm Sci 99:246–254PubMedCrossRefGoogle Scholar
  195. Lin SY (2014) Molecular perspectives on solid-state phase transformation and chemical reactivity of drugs: metoclopramide as an example. Drug Discov Today 52:1224–1232. doi: 10.1016/j.drudis.2014.10.001 Google Scholar
  196. Lin SY (2015) Molecular perspectives on solid-state phase transformation and chemical reactivity of drugs: metoclopramide as an example. Drug Discov Today 20:209–222PubMedCrossRefGoogle Scholar
  197. Lin SY, Hsu CH, Sheu MT (2010) Curve-fitting FT-IR studies of loratedine/hydroxypropyl-beta-cyclodextrin inclusion complex induced by co-grinding. J Pharm Biomed Anal 53:799–803PubMedCrossRefGoogle Scholar
  198. Lin HL, Hsu PC, Lin SY (2013) Theophylline-citric acid co-crystals easily induced by DSC-FTIR microspectroscopy or different storage conditions. Asian J Pharm Sci 8:19–27CrossRefGoogle Scholar
  199. Liu Y, Blackwood D (2012) Sample presentation in rotary tablet press feed frame monitoring by near infrared spectroscopy. Am Pharm Rev May: 1–7Google Scholar
  200. Liu C, Desai KG (2005) Characteristics of rofecoxib-polyethylene glycol 4000 solid dispersions and tablets based on solid dispersions. Pharm Dev Technol 10:467–477PubMedCrossRefGoogle Scholar
  201. Löbmann K, Laitinen R, Grohganz H et al (2011) Coamorphous drug systems: enhanced physical stability and dissolution rate of indomethacin and naproxen. Mol Pharm 8:1919–1928PubMedCrossRefGoogle Scholar
  202. Löbmann K, Laitinen R, Grohganz H et al (2013) A theoretical and spectroscopic study of co-amorphous naproxen and indomethacin. Int J Pharm 453:80–87PubMedCrossRefGoogle Scholar
  203. Lourenco V, Lochmann D, Reich G et al (2012) A quality by design study applied to an industrial pharmaceutical fluid bed granulation. Eur J Pharm Biopharm 81:438–447PubMedCrossRefGoogle Scholar
  204. Lumpi D, Wagner C, Schoepf H et al (2012) Fibre-optic ATR-IR spectroscopy at cryogenic temperatures: in-line reaction monitoring on organolithium compounds. Chem Commun 48:2451–2453CrossRefGoogle Scholar
  205. Luo S, Zhang E, Su Y et al (2011) A review of NIR dyes in cancer targeting and imaging. Biomaterials 32:7127–7138PubMedCrossRefGoogle Scholar
  206. Luukkonen P, Fransson M, Bjorn IN et al (2008) Real-time assessment of granule and tablet properties using in-line data from a high shear granulation process. J Pharm Sci 97:950–959PubMedCrossRefGoogle Scholar
  207. Luypaert J, Massart DL, Vander Heyden Y (2007) Near-infrared spectroscopy applications in pharmaceutical analysis. Talanta 72:865–883PubMedCrossRefGoogle Scholar
  208. Ma CY, Wang XZ (2011) Simultaneous characterization of multiple properties of solid and liquid phases in crystallization processes using NIR. Particuology 9:589–597CrossRefGoogle Scholar
  209. Macfhionnghaile P, Hu Y, Gniado K et al (2014) Effects of ball-milling and cryomilling on sulfamerazine polymorphs a comparative study. J Pharm Sci 103:1766–1778PubMedCrossRefGoogle Scholar
  210. Maesschalck RD, Sanchez FC, Massart DL et al (1998) On-line monitoring of powder blending with near-infrared spectroscopy. Appl Spectrosc 52:725–731CrossRefGoogle Scholar
  211. Mallamace F, Baglioni P, Corsaro C et al (2014) The influence of water on protein properties. J Chem Phys 141:165104PubMedCrossRefGoogle Scholar
  212. Maltesen MJ, van der Weert M, Grohganz H (2012) Design of experiments-based monitoring of critical quality attributes for the spray-drying process of insulin by NIR spectroscopy. AAPS PharmSciTech 13:747–755PubMedPubMedCentralCrossRefGoogle Scholar
  213. Manikwar P, Majumdar R, Hickey JM et al (2013) Correlating excipient effects on conformational and storage stability of IgG1 monoclonal antibody with local dynamics as measured by hydrogen/deuterium-exchange mass spectrometry. J Pharm Sci 102:2136–2151PubMedCrossRefGoogle Scholar
  214. Maniruzzaman M, Islam MT, Moradiya HG et al (2014) Prediction of polymorphic transformations of paracetamol in solid dispersions. J Pharm Sci 103:1819–1828PubMedCrossRefGoogle Scholar
  215. Manning MC (2005) Use of infrared spectroscopy to monitor protein structure and stability. Expert Rev Proteomics 2:731–743PubMedCrossRefGoogle Scholar
  216. Mantanus J, Ziémons E, Lebrun P et al (2009) Moisture content determination of pharmaceutical pellets by near infrared spectroscopy: method development and validation. Anal Chim Acta 642:186–192PubMedCrossRefGoogle Scholar
  217. Mantanus J, Ziémons E, Lebrun P et al (2010a) Active content determination of non-coated pharmaceutical pellets by near-infrared spectroscopy: method development, validation and reliability evaluation. Talanta 80:1750–1757PubMedCrossRefGoogle Scholar
  218. Mantanus J, Ziemons E, Rozet E et al (2010b) Building the quality into pellet manufacturing environment—feasibility study and validation of an in-line quantitative near infrared (NIR) method. Talanta 83:305–311PubMedCrossRefGoogle Scholar
  219. Märk J, Karner M, Andre M et al (2010) Online process control of a pharmaceutical intermediate in a fluidized-bed drier environment using near-infrared spectroscopy. Anal Chem 82:4209–4215PubMedCrossRefGoogle Scholar
  220. Markl D, Wahl PR, Menezes JC et al (2013) Supervisory control system for monitoring a pharmaceutical hot melt extrusion process. AAPS PharmSciTech 14:1034–1044PubMedPubMedCentralCrossRefGoogle Scholar
  221. Martens H, Naes T (2001) Multivariate calibration, Copyright 1989 by Wiley, reprinted with correctionsGoogle Scholar
  222. Martínez L, Peinado A, Liesum L et al (2013) Use of near-infrared spectroscopy to quantify drug content on a continuous blending process: influence of mass flow and rotation speed variations. Eur J Pharm Biopharm 84:606–615PubMedCrossRefGoogle Scholar
  223. Maruao K, Tsurugi M, Chin J et al (2003) Noninvasive blood glucose assay using a newly developed near-infrared system. IEEE J Sel Top Quantum Electron 9:322–330CrossRefGoogle Scholar
  224. Marziano I, Sharp DCA, Dunn PJ et al (2000) On-line mid-IR spectroscopy as a real-time approach in monitoring hydrogenation reactions. Org Process Res Dev 45:357–361CrossRefGoogle Scholar
  225. Maury M, Murphy K, Kumar S et al (2005) Spray-drying of proteins: effects of sorbitol and trehalose on aggregation and FT-IR amide I spectrum of an immunoglobulin G. Eur J Pharm Biopharm 59:251–261PubMedCrossRefGoogle Scholar
  226. McArdle P, Gilligan K, Cunningham D et al (2005) Determination of the polymorphic forms of bicifadine hydrochloride by differential scanning calorimetry-thermogravimetric analysis, X-ray powder diffraction, attenuated total reflectance-infrared spectroscopy, and attenuated total reflectance-near-infrared spectroscopy. Appl Spectrosc 59:1365–1371PubMedCrossRefGoogle Scholar
  227. McAucliffe MAP, O’Mahony GE et al (2015) The use of PAT and off-line methods for monitoring of roller compacted ribbon and granule properties with a view to continuous processing. Org Process Res Dev 19(1):158–166. doi: 10.1021/op5000013 CrossRefGoogle Scholar
  228. McFearin CL, Sankaranarayanan J, Almutin A (2011) Application of fiber optic ATR-FTIR methods for in situ characterization of protein delivery systems in real time. Anal Chem 83:3943–3949PubMedPubMedCentralCrossRefGoogle Scholar
  229. Minnich CB, Buskens P, Steffens HC, Bäuerlein PS, Butvina LN, Küpper L, Leitner W, Liauw MA, Greiner L (2007) Highly flexible fibre-optic ATR-IR probe for inline reaction monitoring. Org Process Res Dev 11:94–97CrossRefGoogle Scholar
  230. Möltgen CV (2014) QbD/PAT method development for enhanced process understanding and control of a pharmaceutical pan coating process. Dissertation, University of HeidelbergGoogle Scholar
  231. Möltgen CV, Puchert T, Menezes JC et al (2012) A novel in-line NIR spectroscopy application for the monitoring of tablet film coating in an industrial scale process. Talanta 92:26–37PubMedCrossRefGoogle Scholar
  232. Möltgen CV, Herdling T, Reich G (2013) A novel multivariate approach using science-based calibration for direct coating thickness determination in real-time NIR process monitoring. Eur J Pharm Biopharm 85:1056–1063Google Scholar
  233. Moes JJ, Ruijken MM, Gout E et al (2008) Application of process analytical technology in tablet process development using NIR spectroscopy: Blend uniformity, content uniformity and coating thickness measurements. Int J Pharm 357: 108–118Google Scholar
  234. Momose W, Imai K, Yokota S et al (2011) Process analytical technology applied for end-point detection of pharmaceutical blending by combining two calibration-free methods: simultaneously monitoring specific near-infrared peak intensity and moving block standard deviation. Powder Technol 210:122–131CrossRefGoogle Scholar
  235. Moorthy BS, Schultz SG, Kim SG et al (2014) Predicting protein aggregation during storage in lyophilized solids using solid state amide hydrogen/deuterium-exchange with mass spectrometric analysis (ssHDX-MS). Mol Pharm 11:1869–1879PubMedPubMedCentralCrossRefGoogle Scholar
  236. Moran A, Buckton G (2009) Studies of the crystallization of amorphous trehalose using simultaneous gravimetric vapor sorption/near IR (GVS/NIR) and “modulated” GVS/NIR. AAPS PharmSciTech 10:297–302PubMedPubMedCentralCrossRefGoogle Scholar
  237. Müller UA, Mertes B, Fischbacher C et al (1997) Noninvasive blood glucose monitoring by means of near infrared spectroscopy: methods for improving the reliability of the calibration models. Int J Artif Org 20:285–290Google Scholar
  238. Murphy BM, Zhang N, Payne RW et al (2012) Structure, stability, and mobility of a lyophilized IgG1 monoclonal antibody as determined using second-derivative infrared spectroscopy. J Pharm Sci 101:81–91PubMedCrossRefGoogle Scholar
  239. Muzzio CR, Dini NG, Simionato LD (2011) Determination of moisture content in lyophilized mannitol through glass vials using NIR micro-spectrometers. Braz J Pharm Sci 2:289–297CrossRefGoogle Scholar
  240. Naes T, Isaksson T, Fearn T, Davies T (2002) Multivariate calibration and classification. NIR Publications, ChichesterGoogle Scholar
  241. Nagy ZK, Braatz RD (2012) Advances and new directions in crystallization control. Annu Rev Chem Biomol Eng 3:55–75PubMedCrossRefGoogle Scholar
  242. Nagy ZK, Fujiwara M, Braatz RD (2008) Modelling and control of combined cooling and antisolvent crystallization control. J Process Control 18:856–864CrossRefGoogle Scholar
  243. Nagy ZK, Fevotte G, Kramer H et al (2013) Recent advances in the monitoring, modeling and control of crystallization systems. Chem Eng Res Des 91:1903–1922CrossRefGoogle Scholar
  244. Neergaard MS, Nielsen AD, Parshad H et al (2014) Stability of monoclonal antibodies at high-concentration: head-to-head comparison of the IgG1 and IgG4 subclass. J Pharm Sci 103:115–127PubMedCrossRefGoogle Scholar
  245. Nieuwmeyer FJS, Damen M, Gerich A et al (2007) Granule characterization during fluid bed drying by development of a near infrared method to determine water content and median particle size. Pharm Res 24:1854–1861PubMedCrossRefGoogle Scholar
  246. Noda I (1990) Two-dimensional infrared (2D IR) spectroscopy: theory and applications. Appl Spectrosc 44:550–561CrossRefGoogle Scholar
  247. Otsuka M, Tanabe H (2012) Stability test for amorphous materials in humidity controlled 96 well plates by near-infrared spectroscopy. Drug Dev Ind Pharm 38:380–385PubMedCrossRefGoogle Scholar
  248. Otsuka M, Yamane I (2009) Prediction of tablet properties based on near infrared spectra of raw mixed powders by chemometrics: Scale-up factor of blending and tabletting processes. J Pharm Sci 98:4296–4305PubMedCrossRefGoogle Scholar
  249. Otsuka M, Mouri Y, Matsuda Y (2003) Chemometric evalution of pharmaceutical properties of antipyrine granules by near-infrared spectroscopy. AAPS PharmSciTech 4:Article 47Google Scholar
  250. Otsuka M, Tanabe H, Osaki K et al (2007) Chemoinformetrical evalution of dissolution property of indomethacin tablets by near-infrared spectroscopy. J Pharm Sci 96:788–801PubMedCrossRefGoogle Scholar
  251. Otsuka M, Kanai Y, Hattori Y (2014) Real-time monitoring of changes of adsorbed and crystalline water contents in tablet formulation powder containing theophylline anhydrate at various temperatures during agitated granulation by near-infrared spectroscopy. J Pharm Sci 103:2924–2936PubMedCrossRefGoogle Scholar
  252. Ozaki Y (2012) Near infrared spectroscopy—its versatility in analytical chemistry. Anal Sci 28:545–563PubMedCrossRefGoogle Scholar
  253. Park J, Nagapudi K, Vergara C, Ramachander R, Laurence JS, Krishnan S (2013) Effect of pH and excipients on structure, dynamics, and long-term stability of a model IgG1 antibody upon freeze-drying. Pharm Res 30:968–984PubMedCrossRefGoogle Scholar
  254. Patel AD, Luner PE, Kemper MS (2001) Low-level determination of polymorph composition in physical mixtures by near-infrared reflectance spectroscopy. J Pharm Sci 90:360–370PubMedCrossRefGoogle Scholar
  255. Peinado A, Hammond J, Scott A (2011) Development, validation and transfer of a near infrared method to determine in-line the end point of a fluidized drying process for commercial production batches of an approved oral solid dose pharmaceutical product. J Pharm Biomed Anal 54:13–20PubMedCrossRefGoogle Scholar
  256. Perez-Ramos JD, Findlay WP, Peck G et al (2005) Quantitative analysis of film coating in a pan coater based on in-line sensor measurements. AAPS PharmSciTech 6:E127–E136PubMedPubMedCentralCrossRefGoogle Scholar
  257. Pieters S, De Beer T, Kasper JC et al (2012) Near-infrared spectroscopy for in-line monitoring of protein unfolding and its interactions with lyoprotectants during freeze-drying. Anal Chem 84:947–955PubMedCrossRefGoogle Scholar
  258. Pieters S, Saeys W, Van den Kerkhof T et al (2013) Robust calibrations on reduced sample sets for API content prediction in tablets: definition of a cost-effective NIR model development strategy. Anal Chim Acta 761:62–70PubMedCrossRefGoogle Scholar
  259. Pöllänen K, Häkkinen A, Huhtanen M et al (2005) DRIFT-IR for quantitative characterization of polymorphic composition of sulfathiazole. Anal Chim Acta 544:108–117CrossRefGoogle Scholar
  260. Prestrelski SJ, Tedeschi N, Tsutomu A et al (1993) Dehydration-induced conformational transitions in proteins and their inhibition by stabilizers. Biophys J 65:661–671PubMedPubMedCentralCrossRefGoogle Scholar
  261. Puchert T, Holzhauer CV, Menezes JC et al (2011) A new PAT/QbD approach for the determination of blend homogeneity: combination of on-line NIRS analysis with PC Scores Distance Analysis (PC-SDA). Eur J Pharm Biopharm 78:173–182PubMedCrossRefGoogle Scholar
  262. Qiao N, Li M, Schlindwein W et al (2011) Pharmaceutical cocrystals: an overview. Int J Pharm 419:1–11PubMedCrossRefGoogle Scholar
  263. Quyet PV, Samanta AK, Liew CV et al (2013) A prediction model for monitoring ribbed roller compacted ribbons. J Pharm Sci 102:2667–2678PubMedCrossRefGoogle Scholar
  264. Radtke G, Knop K, Lippold C (1999) In-process control of direct pelletisation in the rotary fluidized bed using NIR spectroscopy. NIR News 10:4–12CrossRefGoogle Scholar
  265. Rahman Z, Zidan AS, Khan MA (2010a) Formulation and evaluation of a protein-loaded solid dispersion by non-destructive methods. AAPS J 12:158–170PubMedPubMedCentralCrossRefGoogle Scholar
  266. Rahman Z, Zidan AS, Khan MA (2010b) Risperidone solid dispersion of orally disintegrating tablet: its formulation design and non-destructive methods of evaluation. Int J Pharm 400:49–58PubMedCrossRefGoogle Scholar
  267. Rajalahti T, Kvalheim OM (2011) Multivariate data analysis in pharmaceutics: a tutorial review. Int J Pharm 417:280–290PubMedCrossRefGoogle Scholar
  268. Rantanen J, Räsänen E, Tenhunen J et al (2000) In-line moisture measurement during granulation with a four-wavelength near infrared sensor: an evaluation of particle size and binder effects. Eur J Pharm Biopharm 50:271–276PubMedCrossRefGoogle Scholar
  269. Rantanen J, Laine SJ, Antikainen OK, Mannermaa JP, Simula OE, Yliruusi J (2001) Visualization of fluid-bed granulation with self-organising maps. J Pharm Biomed Anal 24:343–352PubMedCrossRefGoogle Scholar
  270. Rantanen J, Wikström H, Turner R et al (2005) Use of in-line near-infrared spectroscopy in combination with chemometrics for improved understanding of pharmaceutical processes. Anal Chem 77:556–563PubMedCrossRefGoogle Scholar
  271. Räsänen E, Sandler N (2007) Near infrared spectroscopy in the development of solid dosage forms. J Pharm Pharmacol 59:147–159PubMedCrossRefGoogle Scholar
  272. Räsänen E, Rantanen J, Mannermaa JP et al (2003) Dehydration studies using a novel multichamber microscale fluid bed dryer with in-line near-infrared measurement. J Pharm Sci 92:2074–2081PubMedCrossRefGoogle Scholar
  273. Rehder S, Wu JX, Laackmann J et al (2013) A case study of real-time monitoring of solid-state phase transformations in acoustically levitated particles using near infrared and Raman spectroscopy. Eur J Pharm Biopharm 48:97–103Google Scholar
  274. Reich G (2000a) Fast and non-destructive quality control of gelatin capsule shells. In: Proceedings of third world meeting APV/APGI, Berlin, 3–6 April, pp 493–494Google Scholar
  275. Reich G (2000b) Use of NIR transmission spectroscopy for nondestructive determination of tablet hardness. In: Proceedings of third world meeting APV/APGI, Berlin, 3–6 April, pp 105–106Google Scholar
  276. Reich G (2001) Nondestructive determination of tablet hardness and consolidation characteristics using NIR transmission spectroscopy. Poster presented at AAPS Annual Meeting and Exposition, Denver, M 2283Google Scholar
  277. Reich G (2004) Formulation and physical properties of soft capsules. In: Podczeck F, Jones BE (eds) Pharmaceutical capsules, 2nd edn. Pharmaceutical Press, LondonGoogle Scholar
  278. Reich G (2005) Near-infrared spectroscopy and imaging: basic principles and pharmaceutical applications. Adv Drug Deliv Rev 57:1109–1143PubMedCrossRefGoogle Scholar
  279. Reich G, Frickel H (1999) Use of transmission spectroscopy to determine physical and functional film coat properties on tablets. Proc Int Symp Control Rel Bioact Mater 26:905–906Google Scholar
  280. Reich G, Frickel H (2000) NIR spectroscopy—a rapid method to evaluate gastroresistance and drug release kinetics of film-coated tablets. In: Proceedings of third world meeting APV/APGI, Berlin, 3/6 April, pp 627–628Google Scholar
  281. Remmele RL, Stushnoff C, Carpenter JF (1997) Real-time in situ monitoring of lysozyme during lyophilization using infrared spectroscopy: dehydration stress in the presence of sucrose. Pharm Res 14:1548–1555PubMedCrossRefGoogle Scholar
  282. Robinson MR, Eaton RP, Haaland DM et al (1992) Noninvasive glucose monitoring in diabetic patients: a preliminary evaluation. Clin Chem 38:1618–1622PubMedGoogle Scholar
  283. Römer M, Heinamaki J, Miroshnyk I et al (2007) Phase transformations of erythromycin A dehydrate during pelletisation and drying. Eur J Pharm Biopharm 67:246–252PubMedCrossRefGoogle Scholar
  284. Römer M, Heinämäki JI, Strachan CJ et al (2008) Prediction of tablet film-coating thickness using a rotating plate coating system and NIR spectroscopy. AAPS PharmSciTech 9:1047–1053PubMedPubMedCentralCrossRefGoogle Scholar
  285. Rosas JG, de Waard H, De Beer T et al (2014) NIR spectroscopy for the in-line monitoring of a multicomponent formulation during the entire freeze-drying process. J Pharm Biomed Anal 97:39–46PubMedCrossRefGoogle Scholar
  286. Saeed M, Probst L, Betz G (2011) Assessment of diffuse transmission and reflection modes in near-infrared quantification—Part 2: Diffuse reflection information depth. J Pharm Sci 100:1130–1141Google Scholar
  287. Saerens L (2013) Spectroscopic process monitoring for quality assessment, visualization and understanding of pharmaceutical hot-melt extrusion. PhD Thesis, Ghent UniversityGoogle Scholar
  288. Saerens L, Dierickx L, Quinten T et al (2012) In-line NIR spectroscopy for the understanding of polymer-drug interaction during pharmaceutical hot-melt extrusion. Eur J Pharm Biopharm 81:230–237PubMedCrossRefGoogle Scholar
  289. Saerens L, Vervaet C, Remon JP et al (2014) Process monitoring and visualization solutions for hot-melt extrusion: a review. J Pharm Pharmacol 66:180–203PubMedCrossRefGoogle Scholar
  290. Sandler N, Rantanen J, Heinamaki J et al (2005) Pellet manufacturing extrusion-spheronization using process analytical technology. AAPSPharmSciTech 6:Article 26Google Scholar
  291. Sanzida N, Nagy ZK (2013) Iterative learning control for the systematic design of supersaturation controlled batch crystallization processes. Comput Chem Eng 59:11–121CrossRefGoogle Scholar
  292. Sarracuga MC, Lopez JA (2009) The use of net analyte signal (NAS) in near infrared spectroscopy pharmaceutical applications: interpretability and figures of merit. Anal Chim Acta 642:179–185CrossRefGoogle Scholar
  293. Sarraguca MC, Ribeiro PR, Santos AQ et al (2014) A PAT approach for on-line monitoring of pharmaceutical co-crystals formation with near infrared spectroscopy. Int J Pharm 471:478–484PubMedCrossRefGoogle Scholar
  294. Savolainen M, Heinz A, Strachan C et al (2007a) Screening for differences in the amorphous state of indomethacin using multivariate visualization. Eur J Pharm Sci 30:113–123PubMedCrossRefGoogle Scholar
  295. Savolainen M, Jouppila K, Pajamo O et al (2007b) Determination of amorphous content in the pharmaceutical process environment. J Pharm Pharmacol 59:161–170PubMedCrossRefGoogle Scholar
  296. Schaefer C, Lecomte C, Clicq D et al (2013) On-line near infrared spectroscopy as a process analytical (PAT) tool to control an industrial seeded API crystallization. J Pharm Biomed Anal 83:194–201PubMedCrossRefGoogle Scholar
  297. Schaefer C, Clicq D, Lecomte C et al (2014) A Process Analytical Technology (PAT approach to control a new API manufacturing process: development, validation and implementation. Talanta 120:114–125PubMedCrossRefGoogle Scholar
  298. Scheibelhofer O, Balak N, Koller DM et al (2013) Spatially resolved monitoring of powder mixing processes via multiple NIR probes. Powder Technol 243:161–170CrossRefGoogle Scholar
  299. Schneider H, Reich G (2011a) PAT instrumentation of a suspension dryer for dynamic inline monitoring of solid-liquid separation, washing and thermal drying. Pharm Ind 73:927–936Google Scholar
  300. Schneider H, Reich G (2011b) Optimization of near-infrared spectroscopic process monitoring at low signal-to-noise ratio. Anal Chem 83:2172–2178PubMedCrossRefGoogle Scholar
  301. Schneider H, Reich G (2012) Comparison of different probe arrangements for inline NIR measurements during fluid bed granulation. Paper presented at 26th international forum of process analytical technology (IFPAC), Baltimore, 22–25 January 2012Google Scholar
  302. Schöll J, Bonalumi D, Vicum L et al (2006) In situ monitoring and modeling of the solvent-mediated polymorphic transformation of L-glutamic acid. Cryst Growth Des 6:881–891CrossRefGoogle Scholar
  303. Schönbichler SA, Bittner LKH, Weiss AKH et al (2013) Comparison of NIR chemical imaging with conventional NIR, Raman, and ATR-IR spectroscopy for quantification of furosemide crystal polymorphs in ternary powder mixtures. Eur J Pharm Biopharm 84:616–625PubMedCrossRefGoogle Scholar
  304. Schönbrodt T (2004) Near-infrared spectroscopic characterization of monolithic matrix systems for parenteral drug delivery. Dissertation, University of HeidelbergGoogle Scholar
  305. Schönbrodt T, Mohl S, Winter G et al (2006) NIR spectroscopy—a non-destructive analytical tool for protein quantification within lipid implants. J Control Release 114:261–267PubMedCrossRefGoogle Scholar
  306. Schüle S, Frieß W, Bechthold-Peters K et al (2007) Conformational analysis of protein secondary structure during spray-drying of antibody/mannitol formulations. Eur J Pharm Biopharm 65:1–9PubMedCrossRefGoogle Scholar
  307. Sekulic SS, Ward HW, Brannegan DR et al (1996) On-line monitoring of powder blend homogeneity by near-infrared spectroscopy. Anal Chem 68:509–513PubMedCrossRefGoogle Scholar
  308. Sekulic SS, Wakeman J, Doherty P, Hailey PA (1998) Automated system for the on-line monitoring of powder blending processes using near-infrared spectroscopy. Part II: Qualitative approaches to blend evaluation. J Pharm Biomed Anal 17:1285–1309PubMedCrossRefGoogle Scholar
  309. Shah B, Kakumanu VK, Bansal AK (2006) Analytical techniques for quantification of amorphous/crystalline phases in pharmaceutical solids. J Pharm Sci 95:1641–1665PubMedCrossRefGoogle Scholar
  310. Shah RB, Tawakkul MA, Khan MA (2007) Process analytical technology: chemometric analysis of Raman and near-infrared spectroscopic data for predicting physical properties of extended release matrix tablets. J Pharm Sci 96:1356–1365PubMedCrossRefGoogle Scholar
  311. Shi Z, Anderson CA (2010) Pharmaceutical applications of separation of absorption and scattering in near-infrared spectroscopy (NIRS). J Pharm Sci 99:4766–4783PubMedCrossRefGoogle Scholar
  312. Shi Z, Cogdill RP, Short SM et al (2008) Process characterization of powder blending by near-infrared spectroscopy: blend end-points and beyond. J Pharm Biomed Anal 47:738–745PubMedCrossRefGoogle Scholar
  313. Siesler HW (2008) Basic principles of near-infrared spectroscopy. In: Burns DA, Ciuczak EW (eds) Handbook of near-infrared analysis, 3rd edn. CRC Press, Boca RatonGoogle Scholar
  314. Simone E, Saleemi N, Nagy ZK (2015) In situ monitoring of polymorphic transformations using a composite sensor array of Raman, NIR, and ATR-UV/vis spectroscopy, FBRM, and PVM for an intelligent decision support system. Org Process Res Dev 19:167–177CrossRefGoogle Scholar
  315. Simpson MB (2010) Near-infrared spectroscopy for process analytical technology: theory, technology and implementation. In: Bakeev KA (ed) Process analytical technology, 2nd edn. Wiley, ChichesterGoogle Scholar
  316. Soares FL, Carneiro RL (2014) Evaluation of analytical tools and multivariate methods for quantification of co-former crystals in ibuprofen-nicotinamide co-crystals. J Pharm Biomed Anal 89:166–175PubMedCrossRefGoogle Scholar
  317. Soh JP, Boersen N, Carvajal MT et al (2007) Importance of raw material attributes for modeling ribbon and granule properties in roller compaction: multivariate analysis on roll gap and NIR spectral slope as process critical control parameters. J Pharm Innov 2:106–124CrossRefGoogle Scholar
  318. Sorak D, Herberholz L, Iwascek S et al (2012) New developments and application of handheld Raman, mid-infrared and near-infrared spectrometers. Appl Spectrosc Rev 47:83–115CrossRefGoogle Scholar
  319. Stokvold A, Dyrstad K, Libnau FO (2002) Sensitive NIRS measurement of increased moisture in stored hygroscopic freeze dried product. J Pharm Biomed Anal 28:867–873PubMedCrossRefGoogle Scholar
  320. Storme-Paris I, Clarot I, Esposito S et al (2009) Near infrared spectroscopy homogeneity evaluation of complex powder blends in a small-scale pharmaceutical preformulation process, a real life application. Eur J Pharm Biopharm 72:189–198PubMedCrossRefGoogle Scholar
  321. Sulub Y, LoBrutto R, Vivilecchia R et al (2008) Content uniformity determination of pharmaceutical tablets using five near-infrared reflectance spectrometers: a process analytical technology (PAT) approach using robust multivariate calibration transfer algorithms. Anal Chim Acta 611:143–150PubMedCrossRefGoogle Scholar
  322. Tabasi SH, Fahmy R, Bensley D et al (2008a) Quality by design, Part I: application of NIR spectroscopy to monitor tablet manufacturing process. J Pharm Sci 97:4040–4051PubMedCrossRefGoogle Scholar
  323. Tabasi SH, Fahmy R, Bensley D et al (2008b) Quality by design. Part II: Application of NIR spectroscopy to monitor coating process for pharmaceutical coated product. J Pharm Sci 97:4052–4066PubMedCrossRefGoogle Scholar
  324. Tabasi SH, Fahmy R, Bensley D et al (2008c) Quality by design. Part III: Study of curing process of sustained release polymer products using NIR spectroscopy. J Pharm Sci 97:4067–4086PubMedCrossRefGoogle Scholar
  325. Tabasi SH, Moolchandani V, Fahmy R et al (2009) Sustained release dosage forms dissolution behavior prediction: a study of matrix tablets using NIR spectroscopy. Int J Pharm 382:1–6PubMedCrossRefGoogle Scholar
  326. Tanabe H, Otsuka K, Otsuka M (2007) Theoretical analysis of tablet hardness prediction using chemoinformatric near-infrared spectroscopy. Anal Sci 23:857–862Google Scholar
  327. Tang XC, Pikal MJ, Taylor LS (2002) A spectroscopic investigation of hydrogen bond patterns in crystalline and amorphous phases in dihydropyridine calcium channel blockers. Pharm Res 19: 477–483Google Scholar
  328. Taylor LS, Zografi G (1997) Spectroscopic characterization of interactions between PVP and indomethacin in amorphous molecular dispersions. Pharm Res 12:1691–1698CrossRefGoogle Scholar
  329. Telikepalli SN, Kumru OS, Kalonia C et al (2014) Structural characterization of IgG1 mAb aggregates and particles generated under various stress conditions. J Pharm Sci 103:796–809PubMedPubMedCentralCrossRefGoogle Scholar
  330. Telikepalli S, Kumru OS, Kim JH et al (2015) Characterization of the physical stability of a lyophilized IgG1 mAb after accelerated shipping-like stress. J Pharm Sci 104:495–507PubMedCrossRefGoogle Scholar
  331. Tian F, Middaugh R, Offerdahl T et al (2007) Spectroscopic evaluation of the stabilization of humanized monoclonal antibodies in amino acid formulations. Int J Pharm 335:20–31PubMedCrossRefGoogle Scholar
  332. Tok A, Goh XP, Ng W et al (2008) Monitoring granulation rate processes using three PAT tools in a pilot-scale fluidized bed. AAPS PharmSciTech 9:1083–1091PubMedPubMedCentralCrossRefGoogle Scholar
  333. Touil A, Peczalski R, Zagrouba F (2012) Monitoring of theophylline dehydration in a vacuum contact dryer by near-infrared spectroscopy. Chem Eng Res Des. doi: 10.1016/j.cherd.2012.11.014
  334. Trnka H, Palou A, Panouillot PE et al (2014) Near-infrared imaging for high-throughput screening of moisture induced changes in freeze-dried formulations. J Pharm Sci 103:2839–2846PubMedCrossRefGoogle Scholar
  335. Tumuluri SV, Prodduturi S, Crowley MM et al (2004) The use of near-infrared spectroscopy for the quantification of a drug in hot-melt extruded films. Drug Dev Ind Pharm 30:505–5011PubMedCrossRefGoogle Scholar
  336. Uchida H, Otsuka M (2011) Quantitative analysis of pseudopolymorphic transformation of imidafenacin by application of a novel combination of near-infrared spectroscopy and a humidity-controlled 96-well plate. J Pharm Pharmacol 63:911–917PubMedCrossRefGoogle Scholar
  337. USFDA (2004a) PAT—a framework for innovative pharmaceutical development, manufacturing, and quality assurance.
  338. USFDA (2004b) Final report on pharmaceutical cGMPs for the 21st century—a risk-based approach.
  339. USFDA Draft Guidance—Development and submission of near infrared analytical procedures, Guidance for Industry, March (2015)Google Scholar
  340. Van de Weert M, van’t Hof R, van der Weerd J et al (2000) Lysozyme distribution and conformation in a biodegradable polymer matrix as determined by FTIR techniques. J Control Release 68:31–40PubMedCrossRefGoogle Scholar
  341. Van de Weert M, Haris PI, Hennink WE et al (2001) Fourier transform infrared spectroscopic analysis of protein conformation: effect of sampling method and stress factors. Anal Biochem 297:160–169PubMedCrossRefGoogle Scholar
  342. Van de Weert M, van Dijkhuizen-Radersma R, Bezemer JM et al (2002) Reversible aggregation of lysozyme in a biodegradable amphiphilic multiblock copolymer. Eur J Pharm Biopharm 54:89–93PubMedCrossRefGoogle Scholar
  343. Vanarase AU, Alcalà M, Jerez Rozo JI et al (2010) Real-time monitoring of drug concentration in a continuous powder mixing process using NIR spectroscopy. Chem Eng Sci 65:5728–5733CrossRefGoogle Scholar
  344. Vanarase AU, Järvinen M, Paaso J et al (2013) Development of a methodology to estimate error in the on-line measurements of blend uniformity in a continuous powder mixing process. Powder Technol 241:263–271CrossRefGoogle Scholar
  345. Vercruysse J, Toiviainen M, Fonteyne M et al (2014) Visualization and understanding of the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging. Eur J Pharm Biopharm 86:383–392PubMedCrossRefGoogle Scholar
  346. Vonhoff S, Condliffe J, Schiffter H (2010) Implementation of an FTIR calibration curve for fast and objective determination of changes in protein secondary structure during formulation development. J Pharm Biomed Anal 51:39–45PubMedCrossRefGoogle Scholar
  347. Vora KL, Buckton G, Clapham D (2004) The use of dynamic vapour sorption and near infra-red spectroscopy (DVS-NIR) to study the crystal transitions of theophylline and the report of a new solid-state transition. Eur J Pharm Sci 22:97–105PubMedCrossRefGoogle Scholar
  348. Wahl PR, Treffer D, Mohr S et al (2013) Inline monitoring and a PAT strategy for pharmaceutical hot melt extrusion. Int J Pharm 455:159–168PubMedCrossRefGoogle Scholar
  349. Wahl PR, Fruhmann G, Sacher S et al (2014) PAT for tableting: inline monitoring of API and excipients via NIR spectroscopy. Eur J Pharm Biopharm 87:271–278PubMedCrossRefGoogle Scholar
  350. Wang SL, Wong YC, Cheng WT et al (2010a) A continuous process for solid-state dehydration, amorphization and recrystallization of metoclopramide HCl monohydrate studied by simultaneous DSC-FTIR microspectroscopy. J Therm Anal Calorim 104:261–264CrossRefGoogle Scholar
  351. Wang B, Cicerone MT, Aso Y et al (2010b) The impact of thermal treatment on the stability of freeze-dried amorphous pharmaceuticals: II. Aggregation in an IgG1 fusion protein. J Pharm Sci 99:683–700PubMedCrossRefGoogle Scholar
  352. Ward HW, Blackwood DO, Polizzi M et al (2013) Monitoring blend potency in a tablet press feed frame using near infrared spectroscopy. J Pharm Biomed Anal 80:18–23PubMedCrossRefGoogle Scholar
  353. Warnecke S, Rinnan A, Alleso M et al (2013) Measurement of active content in escitaopram tablets ny near-infrared transmission spectroscopy model that encompasses batch variability. J Pharm Sci 102:1268–1280PubMedCrossRefGoogle Scholar
  354. Wartewig S, Neubert RHH (2005) Pharmaceutical applications of mid-IR and Raman spectroscopy. Adv Drug Deliv Rev 57:1144–1170PubMedCrossRefGoogle Scholar
  355. Weißner BV (2006) Quantitative NIR Kalibrationsmodelle zur nichtinvasiven Tablettenanalytik in der pharmazeutischen Entwicklung und Produktion. Dissertation, Universität HeidelbergGoogle Scholar
  356. Weißner BV, Henck JO, Reich G (2006a) Development of reliable NIR calibration models for nondestructive dissolution testing. Poster presented at the AAPS Annual Meeting and Exposition, San Antonio, R 6010Google Scholar
  357. Weißner BV, Henck JO, Reich G (2006b) The potential of near infrared spectroscopy for tablet analysis in industrial formulation development and production. In: Proceedings of 5th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, Geneva/Switzerland, 27–30 March 2006Google Scholar
  358. Weißner BV, Henck JO, Reich G (2007) Applied NIR spectroscopy: a reliable alternative to conventional drug dissolution tests. In: Proceedings of 2nd European Congress on Life Science Process Technology, Nuremberg/Germany, March 2007Google Scholar
  359. Wiss J, Ermini G (2006) Safety improvements of a Grignard reaction by controlling the reactant feed rate by on-line concentration monitoring using NIR. Org Process Res Dev 10:1282–1286CrossRefGoogle Scholar
  360. Wiss J, Länzlinger M, Wermuth M (2005) Safety improvement of a Grignard reaction using on-line NIR monitoring. Org Process Res Dev 9:365–371CrossRefGoogle Scholar
  361. Workman JJ, Burns DA (2008) Commercial NIR instrumentation. In: Burns DA, Ciuczak EW (eds) Handbook of near-infrared analysis, 3rd edn. CRC Press, Boca RatonGoogle Scholar
  362. Wu J, Luo W, Wang X et al (2013) A new application of WT-ANN method to control the preparation process of metformin hydrochloride tablets by near infrared spectroscopy compared to PLS. J Pharm Biomed Anal 80:186–191PubMedCrossRefGoogle Scholar
  363. Xiabo Z, Jiewen Z, Povey MJW et al (2010) Variables selection methods in near-infrared spectroscopy. Anal Chim Acta 667:14–32CrossRefGoogle Scholar
  364. Xiang D, LoBrutto R, Cheney J et al (2009a) Evaluation of transmission and reflection modalities for measuring content uniformity of pharmaceutical tablets with near-infrared spectroscopy. Appl Spectrosc 63:33–47PubMedCrossRefGoogle Scholar
  365. Xiang D, Konigsberger M, Wabuyele B et al (2009b) Development of robust quantitative methods by near-infrared spectroscopy for rapid pharmaceutical determination of content uniformity in complex tablet matrix. Analyst 134:1405–1415PubMedCrossRefGoogle Scholar
  366. Xiang D, Berry J, Buntz S et al (2009c) Robust calibration design in the pharmaceutical quantitative measurements with near-infrared (NIR) spectroscopy: avoiding the chemometric pitfalls. J Pharm Sci 98:1155–1166PubMedCrossRefGoogle Scholar
  367. Yang TH, Dong A, Meyer J et al (1999) Use of infrared spectroscopy to assess secondary structure of human growth hormone within biodegradable microspheres. J Pharm Sci 88:161–16PubMedCrossRefGoogle Scholar
  368. Yip WL, Gausemel I, Sande SA et al (2012) Strategies for multivariate modeling of moisture content in freeze-dried mannitol-containing products by near-infrared spectroscopy. J Pharm Biomed Anal 70:202–211PubMedCrossRefGoogle Scholar
  369. Yu ZQ, Chew JW, Chow PS et al (2007) Recent advances in crystallization control: an industrial perspective. IChemE 85:893–905CrossRefGoogle Scholar
  370. Yu J, Zhang X, Hao X et al (2014) Near-infrared fluorescence imaging using organic dye nanoparticles. Biomaterials 35:3356–3364PubMedCrossRefGoogle Scholar
  371. Yuan A, Wu J, Tang X et al (2013) Application of near-infrared dyes for tumor imaging, photothermal, and photodynamic therapies. J Pharm Sci 102:6–28PubMedCrossRefGoogle Scholar
  372. Zhang F, Aaltonen J, Tian F et al (2009) Influence of particle size and preparation methods on the physical and chemical stability of amorphous simvastin. Eur J Pharm Biopharm 71:64–70PubMedCrossRefGoogle Scholar
  373. Zhang GC, Lin HL, Lin SY (2012a) Thermal analysis and FTIR spectral curve-fitting investigation of formation mechanism and stability of indomethacin-saccharin cocrystals via solid-state grinding process. J Pharm Biomed Anal 66:162–169PubMedCrossRefGoogle Scholar
  374. Zhang X, Bloch S, Akers W et al (2012b) Near-infrared molecular probes for in vivo imaging. Curr Protoc Cytom Chapter 12:Unit12.27 doi: 10.1002/04
  375. Zhou X, Hines P, Borer MW (1998) Moisture determination in hygroscopic drug substances by near infrared spectroscopy. J Pharm Biomed Anal 17:219–225PubMedCrossRefGoogle Scholar
  376. Zhou GX, Ge Z, Dorwart J et al (2003) Determination and differentiation of surface and bound water in drug substances by near infrared spectroscopy. J Pharm Sci 92:1058–1065PubMedCrossRefGoogle Scholar
  377. Zhou GX, Crocker L, Xu J et al (2006) In-line measurement of a drug substance via near infrared spectroscopy to ensure a robust crystallization process. J Pharm Sci 95:2337–2347PubMedCrossRefGoogle Scholar
  378. Zidan AS, Rahman Z, Sayeed V et al (2012) Crystallinity evaluation of tacrolimus solid dispersions by chemometric analysis. Int J Pharm 423:341–350PubMedCrossRefGoogle Scholar
  379. Ziémons E, Bourichi H, Mantanus J et al (2011) Determination of binary polymorphic mixtures of fluconazole using near infrared spectroscopy and X-ray powder diffraction: a comparative study based on pre-validation results. J Pharm Biomed Anal 55:1208–1212PubMedCrossRefGoogle Scholar

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© Controlled Release Society 2016

Authors and Affiliations

  1. 1.Department of Pharmaceutical Technology and BiopharmaceuticsInstitute of Pharmacy and Molecular Biotechnology, University of HeidelbergHeidelbergGermany

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