Near Infrared Raman Spectroscopy In Pharmaceutical Analysis Biology Essay

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Raman spectroscopy has found various applications in the recent years. They are used for the depth analysis of the various kinds of motion of the electron for instance rotational, vibration motions in the molecule. They are based on the Raman scattering using laser lights in the UV, infrared or the visible region. When a monochromatic light passes through the material, they are found to have frequency in addition to that of the incident parental frequency.

This effect is based on the phenomenon that laser light interact with the phonons present in the molecules and this will result in the shifting of the frequency of the resultant laser light coming out from the molecule. This phenomenon is based on the inelastic light energy transfer technique between the photons and the energy level of the molecule. When the phonons interact with the molecule, some of the phonons return back to the ground state while others return to the energy state which may be higher or lower than the level from which they were actually excited.

When the photon returns back to the original state, they have the same frequency as the incident frequency. If they return back to higher energy level they are referred as the stokes line while the one that return to the lower energy level are called as the anti storks line. The corresponding frequency of the molecule is called Raman frequency and the line, which originates in addition to the parent line, is called as the Raman line. This principle and the technique can be used to analysis about the sample that has been given under the study in depth. The study in this field has gained interest among the pharmaceutical industries particularly in the last decade due to the advantages that has.

Advantages of this technique

This principle has been used for various kind of application in the real world. Mostly these principles find their applications in the chemistry field as the vibrational and other motion of the molecules are due to the formation of the chemical bonds in the molecule. They are very useful in order to detect the kind of the molecule, as almost all of the molecule will have a particular kind of the vibration. Therefore, this is one of the widely preferred methods in order to determine the identity of the compounds in the molecule.

Three applications of the technique

Application 1: Application of near-infrared and Raman spectroscopy in quantifying the ternary mixtures of Indomethacin in different solid-state forms

What the authors were trying to measure. The authors (Heinz et al, 2007) made several efforts to measure the ternary mixtures of Indomethacin in its diverse forms of solid-state including the amorphous form. For accessing the capability of such techniques, the authors resorted to the option of multivariate analysis in conjunction with vibrational spectroscopy. The strategies that were adopted enumerate the mixtures of γ-, amorphous and α- indomethacins were near-infrared and Raman spectroscopy.

Diagram 1: Structural formula of indomethacin.(Heinz et al, 2007)

How they prepared and ran their samples. This γ -form of indomethacin was attained as per the confirmed method. The process was to dissolve γ -indomethacin in ethanol which is of analytical grade, at a temperature of 80 -C. The heated mixture was subsequently precipitated after the distilled water was added. This was done at the room temperature. The impetuous crystals were removed by the process of filtration and then dehydrated at 36 degree Celsius under vacuum. Amorphous indomethacin was obtained by the subsequent process of melting γ -indomethacin in an aluminum pan with the help of a moisture analyzer at 165-C for 3min. The liquid form of γ -indomethacin was cooled gradually in a dessicator to the ambient temperature over phosphorus pentoxide. This process was executed to prevent atmospheric moisture getting condensed over the sample. The sample was then grounded lightly with pestle and mortar. In order to get the particles of size below 125µm and from 125µm to 250µm, appropriate size sieves were used to pass the amorphous and crystalline forms of indomethacin.

Thirteen mixtures of indomethacin, ternary in nature amorphous and crystalline, (minimum to maximum range of each component) were prepared by geometrically mixing the constituents (1.5 g total). To prevent solid-state changes, the mixing process was conducted gently with a spatula and mortar. The different ratios of γ -indomethacin, α -indomethacin, and amorphous indomethacin were used as given in diagram 2. The storage of mixtures was done over phosphorus pentoxide and the quantifications were conducted on the day of preparation.

Diagram 2: Composition of 13 ternary mixtures consisting of amorphous and crystalline indomethacin (Heinz et al, 2007).

Four analytical techniques viz., x ray powder diffraction (XRPD), Differential scanning calorimetry, Raman Spectroscopy and Near Infrared spectroscopy were used in order to evaluate the mixture.

The key findings of the paper. The key findings of the paper are as follows -

The relative standard deviations for Raman and near-infrared spectroscopy were found to be similar. The outcomes were 12.0% and 13.0 % respectively for these techniques.

The paper showed that when combined with multivariate modeling, both Raman and near-infrared spectroscopies are effective techniques for quick quantification of ternary mixtures. The technique was successfully confirmed for amorphous and crystalline mixtures of indomethcin.

Conclusion. The study infers that the Raman and NIR spectroscopy along with PLS regression are effective in the evaluation of mixtures of amorphous and crystalline indomethacin which are ternary. The study also supplies a strong basis for employing ternary models together with the amorphous form as an analytical process technology tools which can be used to enumerate manifold solid-state alterations in situ during the entire session of the processing.

Application 2: Near-infrared FT-Raman spectroscopy deployed as a rapid analytical tool in determining the diltiazem hydrochloride in tablets

What the authors were trying to measure. The authors (Vergote et al, 2002) are persistently making efforts in order to construct a number of dependable and investigative methods for quantitative confirmation of the diltiazem hydrochloride in the tablets. Although the HPLC is the most preferred method, yet it stands to be very time-consuming because of the extensive

Diagram 3: Chemical formula of Diltiazem hydrochloride (Vergote et al)

level of the preparation of the sample. Scientists are using this FT-Raman Spectroscopy to analyze the diltiazem hydrochloride on a quantitative basis in the tablets that are commercially available such as Tildiem and several other experimental tablets, which are prepared in lab-scale.

How they prepared and ran their samples. Diltiazem hydrochloride was acquired from Sigma. Paraffin wax obtained from Paramelt. The Castor Oil and Magnesium Stearate were obtained from Ludeco. Macrogol 600 was acquired from Federa and the alpha-Lactose monohydrate from the DMV International. Scientists purchased the Diltiazem Hydrochloride tablets from the local drug stores. From Colorcon, they got the pregelatinized com starch or the Starch 1500.

Diagram:4 - The procedure in graphics

The Bruker spectrometer Equinox 55S, was used for the experiment which is equipped with the Raman module of FRA 106 set to a cooled Ge-High sensitivity detector D418-T. The laser wave length during the experiments was 1.064 mm line, from the diode laser pumped Nd-YAG. All the spectra were traced at the resolution of 3 cm and the laser power of 300 m-watt was used for the purpose. All Data collection and Data transportation were done through the software called Bruker OPUS. A motorized positioner was used to focus the laser beam on the sample. This was done to get the highest level of intensity of the Raman Signal. While the experimental tablets were examined as such, the commercial Diltiazem Hydrochloride tablets were analyzed in the blister package. Since the all the results obtained from the FT-Raman spectroscopy have some or the other link in amounts, each of the tablets were appropriately measured to work out the absolute amount of the D-Hydrochloride per tablet.

The key findings of the paper. The key findings of this application are as follows ---

The spectrum of D-Hydrochloride stated the separate signal over the entire spectral range and the most dynamic bands of D-Hydrochloride were detected at 1650-1550 cm. No spectral interference was observed in the region neither from any other compound of the Tildiem Tablets nor from the excipeint used to formulate the matrix tablets.

At the experimental laser power (300 mW) no important changes of the Raman Signal were observed even though the scanning period was increased from a low number of 20 to as high as 500 scans.

The parameters controlling the shapes and position of Raman bands are expected to effect the intensity of the spectral bands are more likely to influence the intensity of the spectral band. The spectra of the calibration at increasing D-Hydrochloride load similar kind of spectra, which were obtained for the drug or lactose calibration tablets, yielding curves for the calculation of the D-Hydrochloride in experimental and commercial tablets of y50.02991x-0.0282 (50.9964) and y50.0313x-0.0600 (R50.9972) respectively.

Conclusion. From the key findings we can easily conclude that FT Raman spectroscopy method is based on the univariate calibration using the peak area measurements is exact for the quantification of the D-Hydrochloride in the tablets. The analysis time was reduced considerably compared to the HPLC analysis as the FT Raman eliminated sample preparation.

Application 3: Detecting Lipitor counterfeits: Comparing Raman and NIR spectroscopy with the combination of chemometrics

What the authors were trying to measure.: Scientists are carrying research on the feasibility of the near infrared or the NIR and the Raman spectroscopy as the rapid screening methods to distinguish between the counterfeits and the genuine features of the medicines that lowers the cholesterol (Lipitor).

How they prepared and ran their samples. The compounds that are studied for this experiment are listed in the table number 1. Each of the batches consists of five tablets. Batches 1 to 9 of the Lipitor tables are of the doses mentioned in the table and obtained from the Pfizer.

Batch

Description

Dose

Analyzed

Tablets

(NIR)

Analyzed

Tablets

(Raman)

API

Origin

1

Reference

10

5

3

Atorvastatine

NL

2

Reference

10

5

3

Atorvastatine

NL

3

Reference

10

5

3

Atorvastatine

NL

4

Reference

20

5

3

Atorvastatine

NL

5

Reference

20

5

3

Atorvastatine

NL

6

Reference

20

5

3

Atorvastatine

NL

7

Reference

40

5

3

Atorvastatine

NL

8

Reference

40

5

3

Atorvastatine

NL

9

Reference

40

5

3

Atorvastatine

NL

10

Reference

20

5

3

Atorvastatine

UK

11

Reference

20

5

3

Atorvastatine

UK

12

Reference

10

5

3

Atorvastatine

Australia

13

Reference

20

5

3

Atorvastatine

Australia

14

Reference

40

5

3

Atorvastatine

Australia

15

Counterfeit

17

5

3

Atorvastatine

IGZ

16

Counterfeit

18

5

3

Lovastatine

IGZ

Table: 1 Indicates the sample reference

Batches 10 and 11 are purchased from UK where as the remaining are collected from Australia. Check the molecular structure of the above mentioned compounds in the following figure.

Diagram 5: The molecular structures of Atrovastatine and Lovastatine.

Near Infrared Spectra were traced on the Spectrum identicheck 'FT-NIR system' equipped with the PBS detector and the identicheck reflectance accessory or the ICRA.

Raman measurements were undergone on the HoloLab Raman Spectrometer, which was equipped with the microscope, a cooled CCD detector and a 785 nm laser.

As the samples were measured as received, The NIR analysis underwent on the front side and the backside as well of the intact tablets, whereas the Raman Scanning was done on the each side of the tablet, after cutting it.

PCA was applied on the 30 Raman Spectra, which was obtained from the line after scanning three tablets to decide the consequence of in homogeneity. This technique was applied as well to study the outcomes of the various types of storage conditions on Raman and NIR spectra.

The key findings of the paper. Key findings of this paper are as follows:

The findings by the PCA of 30 Raman spectra which were obtained from the spectra scans the core if the 'score plot of PC1 vs PC2 in figure diagram 6 details three distinguished tablets.

Diagram 6: Core plot of PC2 vs. PC1 of the PCA of the Raman spectra (line-scan) of batch 15 counterfeit containing atorvastatine (_), batch 16 counterfeit containing lovastatine (+) and batch 5 a genuine Lipitor® reference tablet (_). (Peinder et al, 2007)

Diagram 7: The 2nd principal component (PC) of the PCA model applied to the NIR spectra

of the tablets after 24 h at different storage conditions. (Peinder et al, 2007)

Diagram 8: Effect of storage conditions on the score plot of PC2 vs. the sample number for the NIR spectra of all reference tablets. Desiccator storage (+), stove storage (_), atmospheric storage (_) and freshly unpacked samples (_).(Peinder et al, 2007)

It became easier to distinguish between genuine and counterfeit tablets by using Raman spectroscopy

PLS-DA models were developed for Raman and NIR spectra to differentiate between counterfeits containing Lovastatine or Atorvastatine (batches of 15 and 16) as the API.

Conclusion. Coming to the conclusion part of this write-up we can easily conclude that both the Raman Spectroscopy and Near Infrared in combination with the chemomatric analysis of all the spectral data is a valuable tool to differentiate between the genuine and counterfeit Lipitor tablets.

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