Paediatric Paracetamol Oral Suspension From Different Manufacturers Biology Essay


It is certainly one of the most important analytical techniques. One of the great advantages of infrared Spectroscopy is that virtually any sample state may be studied. Gases, Liquids, solutions, powders, pastes, films, fibres and surfaces can all be examined with a judicious choice of sampling technique. As a consequence of the improved instrumentation, a variety of new sensitive techniques have now been developed in order to examine formerly intractable samples.

Chemical infrared spectroscopy emerged as a science in the 1880s. In the 1890s, A.A. Michelson, to further his studies of the speed of light, invented the interferometer.In the early 1940s, chemical infrared spectroscopy was still an immature scientific Field. But with commercial development of the optical null dispersive

Spectrophotometer, later that decade, chemical infrared spectroscopy came into

Widespread use. Dispersive instruments proved the tremendous value of infrared

Analysis, and soon became the mainstay of organic characterization laboratories.

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In 1949 Peter Fellgett used an interferometer to measure light from

Celestial bodies and produced the first Fourier transform infrared spectrum. But for

Many years, only a few advanced research groups with access to large, expensive

Computers and with personnel able to wait up to 12 hours to transform an

Interferogram into a spectrum used Fourier transform infrared (FTIR) spectroscopy.

FTIR spectrometers were limited to studying problems not Solvable with dispersive techniques.

In the late 1960s when microcomputers able to do the Fourier transform became

Available, commercial FTIR spectrometers appeared. The 1966 development of the

Cooley-Tukey algorithm, which quickly does a Fourier transform (the Fast Fourier

Transform or FFT), was also instrumental in the commercialization of FTIR

Spectrometers. However, the first FTIR spectrometers were large and expensive, and

Were found primarily in a few well to do research labs.

Gradually, technology reduced the cost, increased the availability, and enhanced the

Capabilities of FTIR spectroscopy systems. The performance to price ratio provided

By FTIR spectrometers today was unthinkable only a decade ago.


Infrared radiation lies between the visible and microwave portions of the electromagnetic spectrum.

Infrared waves have wavelengths shorter than microwaves and longer than visible, and have frequencies which are higher than microwaves and lower than visible.

The Infrared region is divided into: near-infrared, mid-infrared and far-infrared.

Near-infrared refers to the part of the infrared spectrum that is closest to visible light.

far-infrared refers to the part that is closer to the microwave region.

Mid-infrared is the region between these two.

The primary source of infrared radiation is thermal radiation (Heat).

It is the radiation produced by the motion of atoms and molecules in an object. The higher the temperature, the more the atoms and molecules move and the more infrared radiation they produce.

Any object radiates in the infrared. Even an ice cube, emits infrared.

The bonds between atoms in the molecule stretch and bend, absorbing infrared energy and creating the infrared spectrum.

Infrared spectroscopy is a technique based on the vibrations of the atoms of a molecule. An infrared spectrum is commonly obtained by passing infrared radiation through a sample and determining what fraction of the incident radiation is absorbed at a particular energy. The energy at which any peak in an absorption spectrum appears corresponds to the frequency of a vibration of a part of a sample molecule. In this introductory chapter, the basic ideas and definitions associated with infrared spectroscopy will be described. The vibrations of molecules will be looked at here, as these are crucial to the interpretation of infrared spectra.

Symmetric Stretch

Antisymmetric Stretch


A molecule such as H2O will absorb infrared light when the vibration (stretch or bend) results in a molecular dipole moment change.

Capabilities of Infrared Analysis

Identification and quantitation of organic solid, liquid or gas samples.

Analysis of powders, solids, gels, emulsions, pastes, pure liquids and solutions, polymers, pure and mixed gases.

Infrared used for research, methods development, quality control and quality assurance applications.

Samples range in size from single fibers only 20 microns in length to atmospheric pollution studies involving large areas.

Applications of Infrared Analysis

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Pharmaceutical research.

Forensic investigations.

Polymer analysis.

Lubricant formulation and fuel additives.

Foods research.

Quality assurance and control.

Environmental and water quality analysis methods.

Biochemical and biomedical research.

Coatings and surfactants.

FTIR (Fourier transform infrared spectroscopy)

It is a technique for collecting infrared spectra. Instead of recording the amount of energy absorbed when the frequency of the infra-red light is varied, the IR light is guided through an interferometer. When the light passes through the sample, the measured signal is the interferogram. Performing a mathematical Fourier transform on this signal results in a spectrum identical to that from conventional infrared spectroscopy.

FTIR is based on the idea of the interference of radiation between two beams to yield an interferogram. The latter is a signal produced as a function of the change of path length between the two beams. The two domains of distance and frequency are interconvertible by the mathematical method of Fourier-transformation. The basic components of an FTIR spectrometer are shown. The radiation emerging from the source is passed through an interferometer to the sample before reaching a detector. Upon amplification of the signal, in which high-frequency contributions have been eliminated by a filter, the data are converted to digital form by an analogy-to-digital converter and transferred to the computer for Fourier-transformation.


Infrared energy is emitted from a glowing black-body source. This beam passes through an aperture which controls the amount of energy presented to the sample (and, ultimately, to the detector).


The beam enters the interferometer where the "spectral encoding" takes place. The resulting interferogram signal then exits the interferometer.


The beam enters the sample compartment where it is transmitted through or reflected off of the surface of the sample, depending on the type of analysis being accomplished. This is where specific frequencies of energy, which are uniquely characteristic of the sample, are absorbed.


The beam finally passes to the detector for final measurement. The detectors used are specially designed to measure the special interferogram signal.


The measured signal is digitized and sent to the computer where the Fourier transformation takes place. The final infrared spectrum is then presented to the user for interpretation and any further manipulation.

Thermo Nicolet Nexus 870. (Instrument type)

Frequency Range : 400-12000 cm-1

Spectral Resolution : 0.125 cm-1

Beam splitters : KBr (375-7000 cm-1).

CaF2 (1100-11000 cm-1).

Far-IR solid substrate ().

Detector : DTGS.


Sources : IR (Globar).

White light (tungsten lamp).

External (Synchrotron).

FT-IR Advantages and Disadvantages


Most measurements by FT-IR are made in a matter of seconds rather than several minutes.


It is dramatically improved with FT-IR for many reasons. The detectors employed are much more sensitive, the optical throughput is much higher which results in much lower noise levels, and the fast scans enable the co addition of several scans in order to reduce the random measurement noise to any desired level

Mechanical Simplicity:

The moving mirror in the interferometer is the only continuously moving part in the instrument. So it is very little possibility of mechanical breakdown.

Internally Calibrated:

These instruments is internal wavelength calibration standard. The instruments are self-calibrating and never need to be calibrated by the user.

Multiplex Advantage (Fellgett's Advantage):

An interferometer does not separate light into individual frequencies before measurement.

This means each point in the interferogram contains information from each wavelength in the input light. In other words, if 8,000 data points along the interferogram are collected, each wavelength in the input light is sampled 8,000 times.

By contrast, a dispersive spectrophotometer that measures 8,000 individual points across a spectrum samples each wavelength only once.

Throughput Advantage (Jacquinot's Advantage):

The simple optical path of the interferometer (no slits and fewer optical elements) means more energy gets to the sample than is possible with dispersive spectrophotometers. This means more energy reaches the detector, increasing the spectrum's potential signal-to-noise ratio.

Also, it is increase the resolution of dispersive instruments, the slits through which light must pass are narrowed, thereby decreasing energy throughput. In FTIR resolution is increased by lengthening the moving mirror stroke length with no decrease in energy throughput. As wavelength resolution increases, the advantages of interferometric versus dispersive measurements increase.

Frequency Precision (Conne's Advantage):

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With dispersive instruments, frequency precision and accuracy depend on: 1) calibration with external standards and 2) the ability of electromechanical mechanisms to uniformly move gratings and slits during and between scans.

The interferometer has an internal frequency standard, generally a helium-neon laser. Also, both mirror movement and detector sampling are clocked by the interferometer fringes from the laser's monochromatic light. All frequencies in the output spectrum are calculated from the known frequency of the laser light.

An FTIR easily achieves frequency precision and accuracy of better than 0.01 wave numbers. This means that spectra collected with an FTIR spectrometer can be quantitatively compared whether they were collected five minutes or five years apart.

Constant Spectral Resolution:

In an FTIR spectrometer, the resolution of the measured spectrum is the same for all frequencies, not varied throughout the spectrum as is often true with dispersive instruments.

Better sensitivity and brightness.

Allows simultaneous measurement over the entire wavenumber range.

Requires no slit device, making good use of the available beam High wavenumber accuracy.

Technique allows high speed sampling with the aid of laser light interference fringes.

Requires no wavenumber correction.

Provides wavenumber to an accuracy of 0.01 cm-1 Resolution.

Provides spectra of high resolution Stray light.

Fourier Transform allows only interference signals to contribute to spectrum.

Background light effects greatly lowers.

Allows selective handling of signals limiting intreference Wavenumber range flexibility

Simple to alter the instrument wavenumber range


It is a white, odourless crystalline powder with a bitter taste, soluble in 70 parts of water, 7 parts of alcohol (95%), 40 parts of glycerol, 13 parts of acetone, 50 parts of chloroform, 9 parts of propylene glycol, or 10 parts of methyl alcohol. Paracetamol is also soluble in solutions of alkali hydroxides. Paracetamol is insoluble in benzene and ether. A saturated aqueous solution has a pH of about 6 and is stable but stability decreases in acid or alkaline conditions, the paracetamol being slowly broken down into acetic acid and p-aminophenol.

Mixtures of paracetamol and aspirin are stable in dry conditions, but tablets in the presence of moisture, magnesium stearate, or codeine, produce some diacetyl-p- aminophenol when stored at room temperature, and this latter compound is hydrolyzed in the presence of moisture to paracetamol and p-aminophenol. It is described as 4-hydroxyacetanilide or N-acetyl-p-aminophenol.In US Pharmacopoeia it is known as acetaminophen.

It is completely absorbed from the gastrointestinal tract and, after oral administration, peak plasma concentrations are reached in less than an hour. The drug is fairly uniformly distributed in the body and approximately 90% of a therapeutic dose is eliminated by conjugation with glucoronic acid in the liver; 3-5% is catabolized to the acid and cysteine conjugates by the P-450 mixed function oxidase enzyme system. All of these metabolites are excreted in the urine and in fact only a slight amount of the drug is excreted unchanged. It is the intermediate metabolites formed during the biotransformation in the liver that are believed to be responsible for the hepatotoxicity of the drug.

The half-life of acetaminophen in normal adults is about 2-3 hours. Because the hepatic conjugation is the rate-determining step in the catabolic pathway, the half-life is found to be longer in patients with liver disease or in the presence of other drugs which compete for the hepatic conjugation mechanism.

It is does not have anti-inflammatory activity and it does not effect blood clotting. Its pain relieving ability is about equal to that of aspirin and it is preferred over aspirin when the homeostatic side effects of aspirin must be avoided.

Pharmacological properties: It consists of the prostaglandins synthesis inhibition, predominant in the hypothalamic thermoregulation center. Analgesic/antipyretic with slight anti-inflammatory action.

Prescribed for: Cephalalgia, Odontalgia, Primary dysmenorrhea, Feverish conditions of diverse provenience. Slight and moderate Algias.

Side effects: Anemia, thrombocytopenia, and allergic reaction.

Drug interactions: When the Acetilcysteine reduces adverse and toxic effects of paracetamol. When increases the hepatotoxic effect of barbiturates, antiepileptics, rifampicine, alcohol, and specific action of nesthyroidien antiinflammatory, indirect anticoagulants.

Mechanism of action

The similarity in structure and effect of paracetamol and aspirin, it has long been assumed that the two act in a similar way: by reducing the activity of the cyclooxygenase (COX) enzyme; this enzyme participates in the production of prostaglandins which in turn are involved in the pain and fever processes.

Important differences between the effects of aspirin and paracetamol: Prostaglandins participate in the inflammation response, and aspirin accordingly inhibits inflammation, but paracetamol does not. Further, COX also produces thromboxanes which aid in blood clotting; aspirin reduces blood clotting, but paracetamol does not. Finally, aspirin and the other NSAIDs can have detrimental effects on the lining of the stomach, where prostaglandins serve a protective role.

Aspirin acts as a Competitive inhibitor of COX and directly blocks the enzyme's active site, Boutaud found that paracetamol indirectly blocks COX, and that this blockade is ineffective in the presence of peroxides. This might explain why paracetamol is effective in the central nervous system and in endothelial cells but not in platelets and immune cells which have high levels of peroxides.


Paracetamol is metabolized primarily in the liver,here most of the drug converted to inactive compounds by conjugation with sulfate and glucuronide, and then excreted by the kidneys. Only a small portion is metabolized via the hepatic cytochrome p450  enzyme system. The toxic effects of paracetamol are due to a minor alkylating metabolite (N-acetyl-p-benzo-quinone imine), not paracetamol itself or any of the major metabolites. This toxic metabolite reacts with sulfhydryl groups. At usual doses, it is quickly detoxified by combining irreversibly with the sulfhydryl group of glutathione to produce a non-toxic conjugate that is eventually excreted by the kidneys.


To study the activity of paracetamol oral suspension by using FTIR instrument by observing the reading on "OMNIC" software (version 7.2).

Chemometric analysis of paracetamol oral suspension by using PCA and Dendrogram methodology.



Paracetamol oral suspensions of three different brand names are taken for my study

Three different paracetamol oral suspentions are:




All the suspensions are of same concentration with different manufacturing years.

I categorised these paracetamol suspensions into two different groups based on manufacturing years.

















Paracetamol suspensions contains the concentration of

120mg/5ml paracetamol.


Paracetamol oral suspensions




FTIR (Fourier transform infrared spectroscopy).

NEXUS (company)

Liquid nitrogen (-400C)

Beam splitter KBR (450)

Software's used for developing statistical data

OMNIC (version 7.2).

Data file conversion standard steps.


InSight 40a (made by : Diknow Technologies).

Instrumentation settings

Type of Detector

MCT (bb)-Mid IR detector.


Range (cm-1) : 420-8000.

D*(cm-1 /W/Hz-1/2) : 5*109

Time constant(s) :10-6 .

Operating temperature (K) :77.

Spectral resolution

The separation of the various spectral wavelengths, usually defined in wave numbers (cm-1). A setting of 4 to 8 cm-1 is sufficient for most solid and liquid samples. For many experiments may need a resolution of 2 cm-1 or higher. Higher resolution experiments will have lower signal-to-noise.

So I used Resolution at: 2cm-1

Number of scans

A complete cycle of movement of the interferometer mirror. The number of scans collected affects the signal-to-noise ratio (SNR) of the final spectrum. The SNR doubles as the square of the number of scans collected; i.e. 1, 4, 16, 64, 256…

Number of scans I used: 2

Type of background (ABSORBANCE)

Scan mode are: single beam or ratio. Single beam can be a scan of the background (no sample) or the sample. Ratio mode always implies the sample spectrum divided by, or ratioed against, the single beam background.




Raman spectroscopy is an analytical technique used for assessing the properties of powder. Liquid nitrogen (-400C) is required to cool the detector. This is added to the top component above the detector.

Lifting liquid nitrogen Dewar is heavy to fill up the transfer container. Pouring liq.Nitrogen into the detector could cause harm if spelled.

Make sure you have fully trained in operating this equipment and feeling fit and well before you use it.

Wear proper PPE (Gloves, Sensible shoes and safety glasses and safety viser).

Ask a colleague to help you in lifting the liquid nitrogen Dewar.

Make sure the liquid nitrogen Dewar is closed properly after you finished with it.

Keep the door slightly open to reduce risk would cause from insufficient ventilation.

Manual Handling training (will be provided).


Change the Beam splitter to KBr.

Open "OMNIC 7.2" [It should start in I.R. mode see box Experiment: (Default)] a message saying "stage initialisation" appears.

Go into COLLECT and select "Experimental Setup" and then select the tab "Bench".

Set the parameters. The detector selected should be "Tec InGaAs" unless Liquid Nitrogen has been used to cool the "MCT/A" detector on the IR.

Get an interferogram (if the FTIR crystal is present this should appear automatically). It may be necessary to reduce the aperture setting (Default is 95, but it may need to be lowered as far as 5).

An interogram should appear.

If this does not appear, select the Diagnostic tab and then "Reset Bench" and "Align". If it still doesn't appear make sure that the crystal is in place, the correct detector is selected and the aperture is correct, than go back and "Reset bench" and Align" again.

Complete your experimental set up. Click on the "Collect" tab and choose the number of accumulating scans, spectral resolutions, background handling and so on. (The most flexible background setting is "collect background after min". Choose an implausible high number e.g.8000.) After press "OK".

Collect background. Go into COLLECT (in the main toolbar) and select "Collect Background". After collecting the spectrum choose "add to window " in the conformation window.

Place your sample on the crystal. Go into COLLECT and select "Collect Sample".

For Serial measurements go to "Experimental Setup" and select SERIES from that select "Series set up". Make settings on the "Collect" and Background" tabs.(Note: "Start collection at external trigger" should be turned off.)

Go to SERIES and select "Collect Series". Set path and choose a filename. A basic vector will be collected. Place your sample on the crystal and start the measurement.

Data Handling: The run will be saved as a *.srs file. To convert it into a text file, go to SERIES and select split file. Open the files with OMNIC and save as *.csv flies.


The software that runs the Nicolet FTIR benches and microscopes on Beam line 1.4 is called OMNIC.


Total Experiment run: 10min/ 1 sample.


Check the signal strength and set the spectrometer parameters.

Go to the Collect Menu >Experiment Setup>Collect Tab.

This will open a new window

For experiment readings are changed like

No. Of scans : 2

Resolution : 2cm-1

Final format : Absorbance.

Background Handling >collect background after 8000minutes.

Go to the Collect Menu >Experiment Setup>bench tab.

Sample compartment : Main.

Detector : MCT/A.

Beamsplitter : KBr

Source : IR.

Accessory : Smart ARK.

Window : ZnSe.

Gain 8 : Auto gain.

Aperture : 4.

Go to the Collect Menu >Experiment Setup>Diagnostic tab.

If need to change bench settings >Reset Bench.

Go to the Collect Menu >Experiment Setup>Series.

Data collection type : Kinetics.

Profiles : Gram-Schmidt.

Time Sequence : Save 10 minutes.

Time ads unit : Minute.

Use repeat time : 60.00 (sec).


Use collect background in the collect menu to collect a background spectrum. A background spectrum measures the response of the spectrometer without a sample in place. During collection a live display of the data appears in the collect background window.

NOTE: Experiment setup provides several options for determining when and how a background spectrum is collected. Depending on the background handling option selected, you may never need to use the collect background command.

A background spectrum is used to eliminate signals that are due to the spectrometer and its environment from the sample spectrum. The background single-beam spectrum shows how the energy of the source is distributed over the displayed frequency range. It includes the

Characteristics of the environment of the spectrometer, including the detector, beam splitter and atmospheric conditions.

Each sample single-beam spectrum is ratioed against the background single-beam spectrum so that the absorptions in the final spectrum are due solely to the sample. The sample spectrum is displayed using the specified final format: for example, aborbance or % transmittance.

When to collect a new background spectrum

Collect a new background spectrum if.....

Any changes in spectrometer hardware.

Changed the settings of any of the following parameters in the experiment setup dialog box.

On the COLLECT tab: Resolution, Automatic Atmospheric suppression.

On the BENCH tab : Velocity,Aperture,samplecompartment,detector,Beamsplitter,source,Accessory,Window,Max range limit,min range limit.

On the ADVANCED tab: Zero filling, Apodizationsample spacing, phase correction, lowpass filter, high pass filter, single-sided interferogram.

File Conversion Steps

File>open Filename.srs ---open

Series>split series files.........(set path : Note Locate your Folder)>ok

File>Open>*.spa(press shift and select all without background)>open

Edit>select all

File>save as>*.csv (note press save [Enter] for number of files).

Insight 40a

Made By: Diknow Technologies.

The limitations in most mainstream software tools based on algorithms such as Partial Least Squares regression, Principal Component Analysis, Alternating Least Squares and Support Vector Machines, prompted us to put together alternative tools.

It is advance practical and intelligent algorithms developed over years of research in multivariate data analysis and deconvolution.


Spectroscopic Monitoring of Solids, Liquids and Gases.

Combinatorial & High Throughput Data Analysis of Chromatographic and Spectroscopic Data.

Pilot Plant Optimization and Fine-Tuning.

Quality Control and Batch Characterization.


Computer with Math Coprocessor.

Matlab® Version 6 and Higher.

Microsoft Excel (Recommended).

Operating System: Microsoft Windows, UNIX.






High Value High Throughput Productivity Tool.

Manuals, Training and Confidential Technical Advice Provided to InSight Users.