10/11/2005 1 ENGINEERING RESEARCH CENTER FOR STRUCTURED ORGANIC PARTICULATE SYSTEMS RUTGERS UNIVERSITY PURDUE UNIVERSITY NEW JERSEY INSTITUTE OF TECHNOLOGY UNIVERSITY OF PUERTO RICO AT MAYAGÜEZ Opening your Mind to Vibrational Opening your Mind to Vibrational Spectroscopy Spectroscopy Rodolfo J. Romañach, Ph.D. UPR-Mayagüez [email protected]May 14, 2012
Opening your Mind to Vibrational Spectroscopy. Rodolfo J. Romañach, Ph.D. UPR-Mayagüez [email protected] May 14, 2012. Regions of Infrared Spectrum: Far Infrared: 650 – 25 c m -1 Mid Infrared: 4000 – 650 c m -1 wavelengths from 2.5 m to 25 m). - PowerPoint PPT Presentation
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10/11/20051
ENGINEERING RESEARCH CENTER FOR
STRUCTURED ORGANIC PARTICULATE SYSTEMSRUTGERS UNIVERSITYPURDUE UNIVERSITYNEW JERSEY INSTITUTE OF TECHNOLOGYUNIVERSITY OF PUERTO RICO AT MAYAGÜEZ
Opening your Mind to Vibrational Opening your Mind to Vibrational SpectroscopySpectroscopy
Spectroscopy of the Solid StateSpectroscopy of the Solid State Spectroscopy - Interaction between radiation
and matter. Spectra – pattern that indicates absorbance or
reflection of radiation as a f(λ) or f(ν). NIR – offers possibility of study of interaction of
solids with radiation since sample preparation is not required.
Need to visualize interaction between particle and radiation. May also be used for liquids, but majority of applications for solids avoiding sample preparation.
Advantages of NIRSAdvantages of NIRS Possibility of using it in a wide range of
applications (physical and chemical), and viewing relationships difficult to observe by other means.
The spectrum may be used to identify the formulation and also to quantify the drug in the formulation.* Cross-sensitivity.
*M. Blanco, J. Coello, A. Eustaquio, H Iturriaga, and S. Maspoch, Development and Validation of a Method for the Analysis of a Pharmaceutical Preparation by Near-Infrared Diffuse Reflectance Spectroscopy, Journal of Pharmaceutical Sciences, 1999, 88(5), 551 – 556.
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Cautions in Working with NIRSCautions in Working with NIRS
Overlapping bands, not easy to interpret. Differences in spectra are often very subtle. May confuse chemical & physical effects. Calibration requires careful experimental design. Depends on accuracy of reference methods. Usually not for trace level analysis. Implementation of NIR requires a significant investment in Human Resources. Not an HPLC !! Over 60% of instruments installed in pharmaceutical companies are never used.
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NIR Absorption BandsNIR Absorption Bands Absorption bands in the NIR are the result of
combination and overtone bands from the fundamental vibrations of C-H, N-H, and O-H bonds seen in the mid-IR.
The overtone and combination bands are 10 – 100 X less intense than the fundamental bands in mid-IR. (Do not confuse energy of vibration with intensity of band).
Differences in spectra are usually very subtle. Instruments have a high signal to noise ratio.
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MIR vs. NIR: Oleic AcidMIR vs. NIR: Oleic AcidAb
sorb
ance
Wavenumber cm-1
Oleic Acid
NIR
MIR
Slide Courtesy Bruker Optics
NIR Bands will be 10 – 100 x weaker than mid-infrared bands
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Fundamentals and Overtones
In the case of the anharmonic oscillator, the vibrational transitions no longer only obey the selection rule n = 1. This type of vibrational transition is called fundamental vibration. Vibrational transitions with n = 2, 3, ... are also possible, and are termed overtones. Called first, second, and so on, overtones.
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Subtle Differences in SpectraSubtle Differences in Spectra
M. Blanco, D. Valdés, I. Llorente, and M. Bayod, “Application of NIR Spectroscopy in Polymorphic Analysis: Study of Pseudo-Polymorphs Stability”, Journal of Pharmaceutical Sciences, 2005, 94(6), 1336 – 1342.
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SummarySummary• NIR spectra are difficult to interpret and
differences in spectra are very subtle, yet it is able to discriminate between spectra of very similar molecules (although the differences are not as easy to discern as in mid-IR).
• Able to provide both chemical and physical information on a samples in the solid state.
• Must work cautiously to avoid confusing chemical and physical information.
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Developing a Calibration Model Developing a Calibration Model • Most NIR calibration models are multivariate. The
absorbance at multiple wavelengths or frequencies are mathematically related to an analyte concentration or physical property.
• Multivariate regression models like MLR, PLS are used, unlike the univariate linear least squares method used in most analytical chemistry.
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X. Zhou, P. Hines, and M.W. Borer, “Moisture Determination in a Hygroscopic drug Substance by Near Infrared Spectroscopy”, Journal of Pharmaceutical and Biomedical Analysis, 17(1998), 219-225.
O-H first overtone
Absorbance, 1st-derivative, and 2nd derivative spectra.
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Variation Implies Information !!
However, variation could come from differences in moisture content (chemical info) or variation in particle size, porosity, density (physical info).
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X. Zhou, P. Hines, and M.W. Borer, “Moisture Determination in a Hygroscopic drug Substance by Near Infrared Spectroscopy”, Journal of Pharmaceutical and Biomedical Analysis, 17(1998), 219-225.
Developing a Chemical Developing a Chemical Quantitative MethodQuantitative Method
• Used Partial Least Squares (PLS) regression to relate changes in water content to changes in the NIR spectra.
• PLS is an example of a multivariate method that uses many responses from the spectrum and relates them to an analytical property.1
• NIR spectra will include variation due to particle size and other physical effects. If you want to measure a chemical property such as concentration then you need to make sure that you are not confusing physical effects with chemical changes. – reason for pretreatment.
1- the methods that we study in analytical chem. class are still univariate)
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Developing a Chemical Quantitative Developing a Chemical Quantitative MethodMethod• Differences in particle size lead to differences in
baseline. • Baseline is not related to concentration. • May eliminate baseline with 1st or 2nd derivative. • The changes observed are more related to
chemical changes after the spectral pretreatment.
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Raw spectra (1100-2205nm) obtained from ribbons of MCC Raw spectra (1100-2205nm) obtained from ribbons of MCC 200 produced at 15 (straight), 25 (dash), and 45 bars (dot). 200 produced at 15 (straight), 25 (dash), and 45 bars (dot).
D, Acevedo, A. Muliadi ,A. Giridhar, J.D. Litster, R. J. Romañach, AAPSPharmscitech, 2012, 13(3), 1005 – 1012, DOI: 10.1208/s12249-012-9825-0.
Spectra subtracted to zero at one λ (baseline corrected).
However, keep effect of pressure on spectrum to develop a NIR model for density.
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Comparison of Sampling VolumeComparison of Sampling Volume
First 2 mm sampled by NIR beam vs.
Entire Sampled Analyzed by HPLC or UV method
Systematic error in the relationship between the optical (NIR) method and the reference method.
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Calibration with ErrorCalibration with ErrorThree types of error:
Random error in the reference laboratory values
Random error in the optical data Systematic error in the relationship
between these two. (e.g. Differences in the sample size of the two methods – sampling error)
From: Principles and Practice of Spectroscopic Calibration – H. Mark, John Wiley & Sons, 1991, p. 17
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The NIR radiation interacts with about 260 mg of sample, the acquisition time is about 0.5 seconds, RMSEP ≈ 0.34 % (w/w).
A.U. Vanarase, M. Alcalà, J.I. Jerez Rozo, F.J. Muzzio and R.J. Romañach, “Real-time monitoring of drug concentration in a continuous powder mixing process using NIR spectroscopy, Chemical Engineering Science, 2010, 65(21), 5728 – 5733.