NIR SPECTROSCOPY AND APPLICATION

Swati Joshi

M.Pharm 1st sem.

INTRODUCTION

Infra-red spectrum is an important record which

gives sufficient information about the structure of a compound. In recent years, NIR spectroscopy

has become so widespread in process analysis and

within pharmaceutical industry for raw material

testing, pharmaceutical industry in biotechnology,

genomics analysis, proteomic analysis ,textile monitoring, food analysis, plastics, textiles, insect detection forensic lab application, crime detection, various military applications,

RANGE OF ELECTROMAGNETIC RADIATION

HISTORY

The history of NIR is begins with WilliamHerschel in18th century. He found the radiant heat beyond the red end while using large glass prism to disperse the sunlight onto the three thermometers having carbon blackened bulbs. The heat is known as “NIR radiation” and the spectrum as “NIR Spectrum”

THEORY AND PRINCIPLE Near-IR (NIR) is a spectroscopic method is based on

molecular overtones and combination vibrations of C-H, O-H and N-H Combinations arise by interaction of two or more vibrations

taking place simultaneously. For a given molecule, a normal mode of vibration

corresponds to internal atomic motions in which all atoms move in phase with same frequency but with different amplitude.

Additionally to these normal vibrations transitions corresponds to be called overtones. Such transitions are forbidden by the selection rules of quantum mechanics. As a result the molar absorptivity in the near IR region is very small.

HOOKE’S LAW

C = speed of light,(2.998 × 1010 )gm sec-2

K = force constant (5 × 105 dynes/cm).

m1 m2 = masses of atom concerned in grams in a perticular bond

o Hooke’s law can be used to calculate the fundamental vibrations for diatomic molecules in IR.

o Transition from the ground state to the first excited state absorbs light strongly in IR region and give rise to intense bands called the fundamental bands.

o Transition from the ground state to the second excited state with the absorption of NIR give rise to weak bands called 1st overtone in NIR.

o Transition from the ground state to the third excited state with the absorption of NIR give rise to weak bands called 2st overtone in NIR.

o Like wise 3rd and 4th overtone bands will occur based on the transition to the fourth and fifth excited state with the absorption of NIR.

NIR is comprised of combinations and overtones that is anharmonic oscillation.

Most molecules contain covalent bonds which

share electrons between atoms. Although bonds are elastic, they do not obey Hooke’s law exactly. The model of anharmonic oscillation is more precise.

Harmonic oscillator can not be retained at larger amplitudes of vibrations owing to repulsive forces between the vibrating atoms and possibility of dissociation..

Electrical anharmonicity: (electrical properties, dipole moment and polarizability).

Mechanical anharmonicity: (nature of molecular vibration).

FRANCK-CONDON PRINCIPLE

The Franck-Condon Principle states that as electrons move very much faster than nuclei, the nuclei as effectively stationary during an electronic transition.

In the ground state, the molecule is most likely in v=0.

The electron excitation is effectively instantaneous; the nuclei do not have a chance to move. The transition is represented by a VERTICAL ARROW on the diagram (R does not change).

The most likely place to find an oscillating object is at its turning point (where it slows down and reverses). So the most likely transition is to a turning point on the excited state.

QUANTUM (MATHEMATICAL) DESCRIPTION OF FC PRINCIPLE

approximately constant with

geometry

Franck-Condon (FC) factor

If electronic excitation is much faster than nuclei move, then wave function cannot change. The most likely transition is the one that has most overlap with the excited state wave function.

INSTUMENTATION

BASIC CONFIGURATIONS OF NIR

Conf B has to be used for multichannel spectroscopy because a wide range spectrum is being simultaneously measured with a multichannel detector.

Conf A is commonly preferred. In the case of interference-filter spectroscopy, it is better because unnecessary components of the light are cut off before the sample position.

LIGHT SOURCES

1.LIGHT EMITTING DIODES(LED) Gallium arsenide

Advantages:- they require low power have Long life expectancy.

2. TUNGSTEN LAMPS (incandescent bulbs) produce heat up to 1100k.

Advantages cheap readily available

2) MONOCHROMATOR:

Two typs of monochromator used1. Prism2. Grating

Grating monochromator is used to measure the full visible and NIR spectrum may be in transmittance or reflectance

It is mainly used for research or when a wide range of different applications is required.

SAMPLES PRESENTAION Transmittance: calculated by dividing the radiant power of

the light transmitted through the sample by the radiant power of the incident light

Reflectance: calculated using the ratio of the radiant power of reflected light to the radiant power of incident light

Transflectance: calculated by dividing the radiant power of light that has traversed a sample twice (once right after it was emitted, and once after if was reflected by a reflector) by the radiant power of the incident light

DETECTORThe choice of detectors depends on Wavelength range, Spectrometer design characterstics detector characteristics such as photosensitivity

(responsivity),noise equivalent power (NEP),etc

Detectors using in NIR spectrometers are

1. Lead sulphide detectos (PbS),

2. Lead selenide detectors (PbSe),

3. Silicon detectors,

4. Indium antimonide detectors,

5. InGaAs, InSb, Common Charged Coupled Devices (CCD).

DETECTORS USED IN NIR SPECTROSCOPY

CLASSIFICATION OF MODERN NIR INSTRUMENTS 

Filter based instruments AOTF based instruments Scaning grating based instruments Fourier-transform based instruments Multichannel Fourier-transform (MCFT)

spectroscopy  

FILTER-BASED INSTRUMENTS A filter allows a particular portion of the spectrum to

pass through or blocks all wavelengths below or above a certain frequency. An interference filter consists of a transparent dielectric spacing material separating two partially reflective windows, allowing a specific set of wavelengths to pass..

source Interference filter sample detector

ACOUSTIC OPTICAL TUNEABLE FILTER In AOTF wavelength selectors light is directed into a

crystal of TeO2 . A high-frequency acoustic wave in the radio frequency range is coupled into the crystal by the use of a piezoelectric material bonded to the crystal. These acoustic waves quickly propagate through the crystal, interact with the broadband light and generate two monochromatic beams of light, each polarized in a different direction.

it has no moving parts,

adjustable intensity and gives narrow

beams

TILTING FILTER It’s first type of interference filter. The transmitted

energy at various wavelength depends on the incident angle of light passing through the filter. In this, the filters were mounted in an encoder wheel for greater accuracy i.e. wavelength reproducibility.

FOURIER TRANSFORM -BASED INSTRUMENTS The interferometer works on the principle whereby light from the

source is split into two segments by the beam-splitter. One portion travels to a fixed mirror and is reflected back to the

splitter and The second portion strikes on a moving mirror and returns to be recombined with the first portion of light.

It’s pattern of peaks/troughs is called an interferogram and by applying mathematical calculations to these, a spectrum evolves. Interferometers are popular in both mid-range infrared and NIR.

MULTICHANNEL FOURIER-TRANSFORM (MCFT) SPECTROSCOPY

This instrument utilizes a fixed monochromator, usually a holographic grating and an array of many small detectors. The light is collimated onto the grating and is thereafter dispersed into component wavelengths. The wavelengths are then directed to a series of photo-diodes. Photo-diode arrays are more commonly used for process control. Fixed monochromator

source sample slit detector

NIR APPLICATIONS

Identification and qualification of raw materials and intermediates.

1. Library approach .2. Conformity approach3. Quantitative calibration models

Analysis of intact dosage forms1. Tablets.2. Capsules3. Lyophilized products4. Polymeric implants and microspheres.

Process monitoring and process control1. Powder blending2. Drying3. Granulation .4. Pelletization5. Tabletting and capsule-filling6. Film coating7. Packaging

NIR AGRICULTURAL APPLICATIONS

it is in commercial use in Japan, primarily for melons and citrus fruit. 

The technology may be used to exclude fruit with internal defects.

A portable unit would enable random checks of fruit in the field or in the wholesale or retail store. 

On-harvester estimation of grain protein content for precision agriculture and estimation of the sugar content of fibrated sugar cane (beet) in sugar mills. 

Sweet Corn - insect damage and insect detection Coal - moisture determination Citrus - quality attributes Pineapples, mango's, strawberries - quality attributes Stone fruit - quality attributes Melons - quality attributes

Determination of pharmaceutical dosage forms Monitoring of PVC industrial blending process Identification of inorganic preservative-treated Wood Analysis of polymorphs Determination of Adulteration of African Essential Oils Protein quantification within lipid implants

LYOPHILIZED PRODUCTS Lyophilization is usually performed to increase the storage

stability of hydrolytically unstable drugs that are intended to be used as injectables or to achieve an instantly soluble oral dosage form.

Normally the moisture content of lyophilized products is determined by time-consuming methods, such as Karl Fischer titration. In addition, the procedure requires the vial to be opened for analysis.

NIR

Moisture determination with NIR diffuse reflectance techniques can be performed in a fast and non invasive manner through the glass vials.

MEASURE THE NIR SPECTRUM OF EACH LYO-PRODUCT

a) The principal set up which to achieve the NIR spectra in reflection mode

b) The illumination is realized through a 40 Watt tungsten halogen lamp which illuminates the vial

c) The NIR reflection is collected in a fibre optic cable which is connected to the NIR PDA spectrometer with 256 diodes and a wavelength range of 1000 nm to 2100 nm

Packaging is the last step in the production line of a pharmaceutical product. To ensure the product safety of pharmaceuticals, a last identity check of the product on the packaging line would be highly desirable.

Such an inspection system based on the combination of a conventional high resolution camera with an on-line diode

NIR spectrometer ranging from 900 to 1700 nm at 6 nm resolution has been developed recently. The system is supposed to perform a 100% identity check at full line speed(i.e. 12,000 tablets per minute) before closing the blister. The potential of this type of equipment has been evaluated in a feasibility study .

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