Professional Documents
Culture Documents
1 Introduction :
Ibuprofen (from the now outdated nomenclature iso-butyl-propanoic-
phenolic acid) is a non-steroidal anti-inflammatory drug (NSAID). It is a colorless
crystalline solid widely used as an analgesic and anti-inflammatory medication. It is
most commonly known as ibuprofen, but is also known as α-methyl-4-(2-
methylpropyl) benzeneacetic acid and 4-isobutyl-@alpha;-methylphenylacetic acid.
Originally marketed as Nurofen, Advil and Motrin and since then under various other
trademarks, most notably Flamex, Profen, Inflam and Reumafen. It is also used for
relief of symptoms of arthritis, primary dysmenorrhea, fever, and as an especially
where there is an inflammatory component. Ibuprofen is known to have an
antiplatelet effect, though it is relatively mild and short-lived when compared to that
of aspirin or other more well-known antiplatelet drugs. Ibuprofen is a core medicine
in the World Health Organization's "Essential Drugs List", which is a list of minimum
medical needs for a basic health care system.
2-(4-isobutylphenyl)propionic Acid
(Ibuprofen)
Figure: Structure of Ibuprofen
Ibuprofen is a relatively safe drug. Because of its effectiveness and lack of side
effects, these are now frequently prescribed by the Doctors.
1.2.1.Conventional treatment:
A currently accepted and widely used treatment for a certain type of
disease, based on the results of past research. Also called conventional treatment.
In this case the drug blood level reached and the time required to
reach that level depend on the dose and the dosing interval. There are several
potential problems inherent in multiple dose therapy.
a) If the dosing interval is not appropriate for the biological half-life of the drug
large “peak” and “valley” in the drug blood level may result, e.g. drugs with
short half-lives require frequent dosing to maintain constant therapeutic
levels.
b) The drug blood level may not be within the therapeutic range at sufficiently
early times an important consideration for certain disease states.
c) Patients’ noncompliance with multiple dosing regimens can result in failure of
this approach.
Those with gastrointestinal risk factors who are unable to take CSIs,
NSAIDs could be prescribed, ideally with an agent to reduce the risk of
gastrointestinal bleeding. The prostaglandin analogue misoprostol or the proton-
pump inhibitor omeprazole have both been shown to reduce the risk of ulcer
complications in patients taking conventional NSAIDs. Unfortunately, the
Pharmaceutical Benefits Scheme in Australia does not currently support the
prophylactic co-prescribing of misoprostol or omeprazole. Conventional doses of H2-
receptor antagonists have not been found to protect patients from adverse
gastrointestinal events.
1.8.Pharmacological Activity:
Ibuprofen have the following pharmacological activity on biological
system. They are:
1. Analgesic
2. Antipyretic
3. Anti-inflammatory effect
1.8.1.Analgesic Activity:
Analgesics are drugs used to control pain without producing loss of
consciousness. Unlike anesthetics, which block all sensation, analgesics do not
affect sensations other than pain. Mild analgesics, such as (Advil), acetaminophen
(Tylenol), and aspirin (e.g., Bayer, Bufferin), work throughout the body at the source
of pain. Researchers think acetaminophen may work at the nerve endings, dulling
the sensation of pain. Ibuprofen and other non-steroidal anti-inflammatory agents
interfere with the production of pain-causing chemicals. Opiate analgesics, such as
codeine and morphine, work within the central nervous system (the brain and spinal
cord). Opiateswork not by relieving the underlying reason for pain, but by changing
the way the individual perceives pain. People who take opiates can become
addicted to them, so these drugs require a doctor's prescription.
1.8.2.Antipyretic Action:
lowering of a raised temperature via decrease in a mediator
prostaglandin which is responsible for elevating the hypothalamic temperature
control.
Antipyretic drug often used to treat malarial fever in endemic areas
is the non-steroidal anti-inflammatory agent ibuprofen. In various studies, ibuprofen
has been shown to be more efficacious than acetaminophen (paracetamol) in
lowering febrile temperatures of infectious origin in children.
Fever represents the most apparent clinical manifestation of
Plasmodium falciparum malaria. The role of fever in defence against malaria or in
other infectious diseases remains a matter of debate. However, it has been shown
that febrile temperatures inhibit the growth of P. falciparum in vitro.
To control fever, the World Health Organization recommends
mechanical measures such as fanning, tepid spoging, and cooling blankets .
However, antipyretic drugs are commonly and widely used to treat malarial fever in
endemic areas, though there is a controversy about the benefit of reducing fever in
children with malaria . Data from Gabon have revealed that neither paracetamol,
nor naproxen or metamizol – antipyretics often used in this area – had an effect on
fever clearance time. Naproxen showed a weak effect in reducing fever peaks and in
reducing the time spent with fever. Worryingly, paracetamol increased parasite-
clearance times (i.e. inhibited clearance of parasites) and significantly decreased
the production of oxygen radicals and tumor necrosis factor, mechanisms of the
innate immune response pivotal to combat infections.
Another antipyretic drug often used to treat malarial fever in
endemic areas is the non-steroidal anti-inflammatory agent ibuprofen. In various
studies, ibuprofen has been shown to be more efficacious than acetaminophen
(paracetamol) in lowering febrile temperatures of infectious origin in children. But
the rationale of its use and its capacity of reducing fever due to P. falciparum
malaria has never been proven in a double blind, placebo controlled trial. In a
randomized, double-blind study in Thai adults, comparing a single dose of ibuprofen
with paracetamol for the treatment of fever due to uncomplicated falciparum
malaria, ibuprofen was significantly more effective than paracetamol in lowering
temperatures throughout the first 4.5 h after dosing, whereas in Malawian children
aged less than five years both drugs were equally effective in reducing fever.
In this double-blind randomized controlled trial, the effect of
ibuprofen on fever compared to placebo in children with uncomplicated P.
falciparum malaria in Gabon was investigated.
1.8.3.Anti-inflammatory effect:
There exists in medical practice at the close of the 20th century
two basic categories of anti-inflammatory drugs: steroidal (from steroid compounds)
and non-steroidal. Steroids are given their own section in this volume. They are
potent inhibitors of inflammation and the immune system, but also have a host of
serious, even deadly, side-effects. The non-steroidal agents are in general less
potent but also have fewer side-effects and will be the subject of this section.
1.9.Metabolism:
Ibuprofen is a non-steroidal anti-inflammatory agent belonging
to a group of propionic acid derivatives. It has three major types of effect which are
all linked to its primary action, the inhibition of an enzyme known as arachidonate
cyclooxygenase or COX of which there are two types COX-1 and COX-2.
The cyclooxygenase pathway:-
Figure: cyclooxygenase pathway
Ibuprofen is metabolized primarily in the liver, where most of it
(60–90% of a therapeutic dose) is converted to inactive compounds by conjugation
with sulfate and glucuronide, and then excreted by the kidneys. Only a small portion
(5–10% of a therapeutic dose) is metabolized via the hepatic cytochrome P450
enzyme system (specifically CYP2E1 and CYP1A2); the toxic effects of ibuprofen are
due to a minor alkylating metabolite (N-acetyl-p-benzo-quinone imine, abbreviated
as NAPQI) that is produced through this enzyme, not ibuprofen itself or any of the
major metabolites. It must be understood however, that there is a great deal of
polymorphism in the P450 gene. Genetic polymorphisms in CYP2D6 have been
studied extensively. The population can be divided into "extensive metabolizes" and
"poor metabolizes" depending on their levels of CYP2D6 expression. Depending on
the drug effects this could be an area of interest for the patient. If the compound
produces a toxic metabolite when metabolized by the P450 system, being an
"extensive metabolize" could lead to adverse effects, whereas being a "poor
metabolize" of a compound whose clearance depends mainly of the P450 system
could as well produce adverse effects. NAPQI is a highly reactive compound that can
lead to formation of protein adducts oxidative stress, and toxicity. Ibuprofen
overdose results in more calls to poison control centers in the US than any other
pharmacological substance. In addition, 35% of cases involving liver failure are
caused by ibuprofen poisoning, according to the American Liver Foundation. The
metabolism of ibuprofen is an excellent example of toxication, because the
metabolite NAPQI is primarily responsible for toxicity rather than ibuprofen itself.
1.10.Dose of Ibuprofen:
Low doses of ibuprofen (200 mg, and sometimes 400 mg) are
available over the counter (OTC) in most countries. Ibuprofen has a dose-dependent
duration of action of approximately 4–8 hours, which is longer than suggested by its
short half-life. The recommended dose varies with body mass and indication.
Generally, the oral dose is 200–400 mg (5–10 mg/kg in children) every 4–6 hours,
adding up to a usual daily dose of 800–1200 mg. 1200 mg is considered the
maximum daily dose for over-the-counter use, though under medical direction, a
maximum daily dose of 3200 mg may sometimes be used in increments of 600–800
mg.
Ibuprofen is also available in topical form, which is absorbed
through the skin, and can be used for sports injuries, with less risk of
gastrointestinal problems.
1.11.Use of Ibuprofen:
• As with other NSAIDs, ibuprofen may be useful in the treatment of severe
orthostatic hypotension.[4]
• In some studies, ibuprofen showed superior results compared to placebo in
the prophylaxis of Alzheimer's disease, when given in low doses over a long
time.[5] Further studies are needed to confirm the results before ibuprofen can
be recommended for this indication.
Ibuprofen has been associated with a lower risk of Parkinson's disease, and may
delay or prevent Parkinson's disease. Aspirin, other NSAIDs, and paracetamol had
no effect on the risk for Parkinson's.[6] Further research is warranted before
recommending ibuprofen for this use.
1.12.Side Effect:
Upset stomach, nausea, vomiting, heartburn, headache,
diarrhea, constipation, drowsiness, and dizziness may occur. If any of these effects
persist or worsen, notify your doctor or pharmacist promptly. Tell your doctor
immediately if any of these serious side effects occur: stomach pain, swelling of the
hands or feet, sudden or unexplained weight gain, ringing in the ears (tinnitus). Tell
your doctor immediately if any of these unlikely but serious side effects occur:
vision changes, rapid or pounding heartbeat, easy bruising or bleeding. Tell your
doctor immediately if any of these highly unlikely but very serious side effects
occur: change in amount of urine, severe headache, very stiff neck, mental/mood
changes, persistent sore throat or fever. This drug may infrequently cause serious
(rarely fatal) bleeding from the stomach or intestines. If you notice any of the
following unlikely but very serious side effects, stop taking ibuprofen and consult
your doctor or pharmacist immediately: black stools, persistent stomach/abdominal
pain, vomit that looks like coffee grounds. This drug may rarely cause serious
(possibly fatal) liver disease. If you notice any of the following highly unlikely but
very serious side effects, stop taking ibuprofen and consult your doctor or
pharmacist immediately: yellowing eyes and skin, dark urine, unusual/extreme
tiredness. An allergic reaction to this drug is unlikely, but seek immediate medical
attention if it occurs. Symptoms of an allergic reaction include: rash, itching,
swelling, severe dizziness, trouble breathing. If you notice other effects not listed
above, contact your doctor or pharmacist.
1.13.Adverse effects:
Ibuprofen appears to have the lowest incidence of
gastrointestinal adverse drug reactions (ADRs) of all the non-selective NSAIDs.
However, this only holds true at lower doses of ibuprofen, so over-the-counter
preparations of ibuprofen are generally labeled to advise a maximum daily dose of
1,200 mg.
Common adverse effects include: nausea, dyspepsia,
gastrointestinal ulceration/bleeding, raised liver enzymes, diarrhea, epistaxis,
headache, dizziness, unexplained rash, salt and fluid retention, and hypertension.[11]
Infrequent adverse effects include: oesophageal ulceration,
heart failure, hyperkalaemia, renal impairment, confusion, bronchospasm, and
rash.[11]
1.14.Drug Interaction:
Before using this medication, tell your doctor or pharmacist
of all prescription and nonprescription products you may use, especially of: oral
bisphosphonates (e.g., alendronate), other medications for arthritis (e.g., aspirin,
methotrexate), "blood thinners" (e.g., warfarin), corticosteroids (e.g., prednisone),
cyclosporine, high blood pressure drugs (including ACE inhibitors such as captopril,
angiotensin II receptor antagonists such as losartan, and beta-blockers such as
metoprolol), lithium, "water pills" (diuretics such as furosemide, hydrochlorothiazide,
triamterene). Check all prescription and nonprescription medicine labels carefully
since many contain pain relievers/fever reducers (NSAIDs such as aspirin, celecoxib,
naproxen) which are similar to this drug and if taken together may increase your
risk for side effects. Low-dose aspirin, as prescribed by your doctor for specific
medical reasons such as heart attack or stroke prevention (usually these dosages
are 81-325 mg per day), should be continued. Consult your doctor or pharmacist for
more details. Do not start or stop any medicine without doctor or pharmacist
approval.
1.15.Over Dose:
If overdose is suspected, contact your local poison control
center or emergency room immediately. Symptoms of overdose may include:
severe stomach pain, coffee ground-like vomit, unusually fast or slow heartbeat,
trouble breathing, extreme drowsiness, loss of consciousness, or seizures.
Ibuprofen overdose has become common since it was licensed for
over-the-counter use. There are many overdose experiences reported in the medical
literature, although the frequency of life-threatening complications from ibuprofen
overdose is low.[19] Human response in cases of overdose ranges from absence of
symptoms to fatal outcome in spite of intensive care treatment. Most symptoms are
an excess of the pharmacological action of ibuprofen and include abdominal pain,
nausea, vomiting, drowsiness, dizziness, headache, tinnitus, and nystagmus. Rarely
more severe symptoms such as gastrointestinal bleeding, seizures, metabolic
acidosis, hyperkalaemia, hypotension, bradycardia, tachycardia, atrial fibrillation,
coma, hepatic dysfunction, acute renal failure, cyanosis, respiratory depression, and
cardiac arrest have been reported.[20] The severity of symptoms varies with the
ingested dose and the time elapsed, however, individual sensitivity also plays an
important role. Generally, the symptoms observed with an overdose of ibuprofen
are similar to the symptoms caused by overdoses of other NSAIDs.
1.16.Photosensitivity:
As with other NSAIDs, ibuprofen has been reported to be a
photosensitising agent.[12][13] However, this only rarely occurs with ibuprofen and it is
considered to be a very weak photosensitising agent when compared with other
members of the 2-arylpropionic acid class. This is because the ibuprofen molecule
contains only a single phenyl moiety and no bond conjugation, resulting in a very
weak chromophore system and a very weak absorption spectrum which does not
reach into the solar spectrum.
1.17.Cardiovascular risk:
Along with several other NSAIDs, ibuprofen has been
implicated in elevating the risk of myocardial infarction, particularly among those
chronically using high doses.[14]
1.18.Risks in pregnancy:
Two studies have found an increased risk of miscarriage with
the use of NSAIDs such as ibuprofen early in pregnancy; however, several other
studies did not find this association. There are also concerns that drugs such as
ibuprofen may interfere with implantation of the early fetus, although a clear risk
has not been established.
When ibuprofen is used as directed in the first and second
trimester of pregnancy, it is not associated with an increased risk for birth defects.
However, ibuprofen is generally not the pain reliever of choice during pregnancy
because there are concerns with the use of ibuprofen during the third trimester.
1.20.Stereochemistry:
Ibuprofen, like other 2-arylpropionate derivatives (including
ketoprofen, flurbiprofen, naproxen, etc), contains a chiral carbon in the α-position of
the propionate moiety. As such, there are two possible enantiomers of ibuprofen,
with the potential for different biological effects and metabolism for each
enantiomer.
Indeed it was found that (S)-(+)-ibuprofen (dexibuprofen) was
the active form both in vitro and in vivo.It was logical, then, that there was the
potential for improving the selectivity and potency of ibuprofen formulations by
marketing ibuprofen as a single-enantiomer product (as occurs with naproxen,
another NSAID).
(R)-ibuprofen (S)-ibuprofen
1.21.Water Solubility:
Ibuprofen is only very slightly soluble in water, less than 1mg of
Ibuprofen dissolves in 1ml water (< 1 mg/mL).[18]
2.Method of study:
2.1.Dissolution:
The time is takes for the drug to dissolve from the dosage form.
Numerous factors affect dissolution. Thus the dissolution medium, agitation,
temperature are carefully controlled. The dissolution medium may be water,
simulated gastric juice, or 0.1M HCL. The temperature is usually 37 degree C. The
apparatus and specifications may be found in the U.S.P. The U.S.P. methods are
official however there is a wide variety of methods based on other apparatus. These
are used because they may be faster, cheaper, easier, sensitive to a particular
problem for a particular drug, or developed by a particular investigator.
Dissolution tests are used as quality control to measure variability
between batches which maybe be reflected by in vivo performance. Thus the in
vitro test may be a quick method of ensuring in vivo performance. Thus there has
been considerable work aimed at defining the in vitro/in vivo correlation.
2.4.Dissolution of Tablets:
Dissolution can be defined as the process by which a drug particle
dissolves and it is important for solid dosage form for absorption.
2.5.Rate of Dissolution:
Dissolution is not always an instantaneous process. It is fast when salt
and sugar dissolve in water but much slower for a tablet of aspirin or a large crystal
of hydrated copper (II) sulfate. The speed at which a solid dissolves may depend on
its crystalline properties (crystalline vs. amorphous, crystal size) and the presence
of polymorphism. This is important in many practical systems, for example in
designing methods for controlled drug delivery. Critically, the dissolution rate
depends on the presence of mixing and other factors that determine the degree of
under saturation in the liquid solvent film immediately adjacent to the solid solute
crystal. In some cases, solubility equilibrium can take a long time to establish
(hours, days, months, or many years; depending on the nature of the solute and
other factors). In practice, it means that the amount of solute in a solution is not
always determined by its thermodynamic solubility, but may depend on kinetics of
dissolution (or precipitation).
The rate of dissolution and solubility should not be confused--they are different
concepts (kinetic and thermodynamic, respectively).
1) Beaker method
2) Flask-stirrer method
3) Rotating basket method
4) Paddle method.
1) That the release of the drug from the tablet is as close as possible to100%
and
2) That the rate of drug release is uniform from batch proven to be bioavilable
and clinically effective.
In case of enteric-coated tablet, the dissolution process gets special importance.
Because in such case, the drug cannot be dissolved in gastric and pH have to be
dissolved within specified time in intestinal fluid.
Dissolve
1000 ml water
Stock solution
4 0.1791
6 0.2738
8 0.3661
10 0.458
12 0.5401
14 0.64512
16 0.7321
0.4
Abs
0.3
Linear (Abs)
0.2
0.1
0
-0.1 0 5 10 15 20
Concentration
2.13 Disintegration:
For immediate release, solid dosage forms, the drug product must
disintegrate into small particles and release the drug. To monitor uniform tablet
disintegration, the united state pharmacopoeia (USP) has established an official
disintegration test. Solid drug products exempted from disintegration tests include
troches, tablets that are intended to be chewed and drug products intended for
sustained released or prolonged or repeat action.
The process of disintegration does not imply complete dissolution of the tablet
and/or the drug. Complete disintegration is define by the USP as “that state in which
any residue of the tablet, expect fragments of insoluble coating, remaining on the
screen of the tablet, except fragments of insoluble coating, remaining on the screen
of the test apparatus in the soft mass have no palpably firm core”. The official
apparatus for the disintegration test and procedure is described in the USP separate
specifications are given for drug products that are designed not to disintegrate.
These products include troches, chewable tablets, and modified released drug
products.
According to BP-2004:
Apparatus-A (for smaller tablet/capsule (18 mm long)
According to USP:
Composition:
1. Basket rack assembly
2. 1000 ml beaker
3. Temperature 37±20 c
4. RPM: 29-32 cycles/min
5. Time: time required for upward stroke≈ downward strok
6. 6 tubes and disc
2.13.1. Result:
After specific time, all tablets have disintegrated completely. If 1-2 tabs fail
to disintegrated, repeat the test on 12 additional tabs. Not less than 16 of the total
18 tablets tested disintegrated completely.
1. Coated tablets
2. Buccal tablets
3. Sublingual tablets
4. Hard gelatin capsules
5. .Soft gelatin capsule
2.14. Evaluation of Tablets:
Evaluation or stability test of tablets or suspension is one of the key
factors for determining the quality of drug substance or drug product. Evaluation of
tablets provides evidence on how the quality of a drug substance or drug product
will maintain within specific time under the influence of a variety of environmental
factors such as temperature, humidity etc and measures and documents the ability
of a product to retain its potency prior to its predicted expectation. These data are
used to determine acceptable shelf life, proper storage conditions. These data also
play a key role in determining labeling instruction as well as determining the
monitoring process. These are also a requirement for manufacturing of regulatory
approved drug.
W1—WL
2.14.4. Thickness:
The thickness of a tablet can vary without any change in weights. This is
generally due to the difference of density of granules, pressure applied for
compression and the speed of compression. The thickeness should be controlled
within ±5 of standard value. In addition, thickness must be controlled to facilitate
packaging. The PTB 311E (511E) Table Testing Instrument is used to determine the
thickness of the individual tablets of each batch.
2.14.5. Hardness:
Tablet requires a certain amount of strength or hardness to withstand
mechanical shocks of handling in manufacture, packaging and shipping. In addition,
tablet should be able to withstand reasonable abuse when in the hands of
consumer. Adequate tablet hardness and resistance to powdering are requisite for
customer acceptance. More recently, the relationship of hardness of tablet
disintegration and perhaps more significantly, to drug dissolution release rate, has
become apparent. The monitoring of tablet hardness is especially important for drug
products that posse’s real or potential bioavailability problems or those are sensitive
to altered dissolution release profiles as a function of the compressive force.
Therefore, It is very necessary to check the hardness of tablets when they are being
compressed and pressure adjusted accordingly on the tablet machine.
There are no specification of hardness of the tablet described on BP or USP. The PTB
311E (511E) Table Testing Instrument is used to determine the hardness of the
individual tablets of each batch.
2.14.6. Friability:
Friability test is performed to valuate the ability of the tablets to
withstand abrasion in packing, handling and transporting .The instrument used for
this test is known as Friabilator.
2.14.6.1 Specification:
• Rotation: 100 times
• Number of Tablets: 20 tablets
• Range: Should be less than < 1 %
• Reference: BP 2003, Volume 4
2.14.7. Disintegration time:
The disintegration test is performed to find out that within how much
time the tablet disintegrates. The test is very important and necessary for all the
tablets, coated or uncoated to be swallowed because the dissolution rate depends
upon the time of disintegration which ultimately affects the rate of absorption of
drugs.
Specification:
• For Uncoated Tablet: 15 Min
• For Coated Tab: 60 Min or 1 Hour.
2.15.Materials:
2.15.1 Apparatus:
Apparatus is the equipment designed to serve a specific function. Apparatus
2.15.2 Funnel:
Funnel is a laboratory apparatus which is used in dispensing a liquid in
a controlled and substantially way to prevent the loss of the sample or substance.
Here, filtration process is facilitate.
2.15.3 Beaker:
A beaker is a simple container for stirring, mixing and heating liquids,
they are commonly used in any laboratory. Beakers are generally cylindrical in
shape, with a flat bottom. Beakers are available in a wide range of sizes, from 1 mL
up to several liters. Beakers are often graduated, marked on the side with lines
indicating the volume contained. For instance, a 250 mL beaker might be marked
with lines to indicate 50, 100, 150, 200, and 250 mL of volume. The accuracy of
these marks can vary from one beaker to another. They may be made of glass or of
plastic.
They may be made of glass (very often Pyrex) or of plastic. Beakers used for holding
solutions of corrosive chemicals, such as acids, should be made of Teflon or other
materials resistant to corrosion, e.g., borosilicate glass.
2.15.4 Pipette:
Pipette is a laboratory instrument used to transport a measured
volume of liquid. Pipettes come in several designs for various purposes with
differing levels of accuracy and precision, from single piece glass pipettes to more
complex adjustable or electronic d by the laboratory funnel
2.16. Instrumentation:
Sophisticated instruments that are used here:
1. Electrobalance
2. The PTB 311(511E) Tablet Testing Instrument
3. Friabilator (Roche)
4. The PTZ Tablet Disintegration Time Testing Instrument.
5. UV-VIS spectrophotometer (DRU-400)
6. The PT-DT (70) Dissolution tester.
7. Tablet compression.
The electro balance provide with the most accurate results. However, errors
do occur when weighing an object on an analytical balance such as:
Figure: Friabilator
The PTZ allows the test of 6 tablets/capsules at the same time within
absolutely identical conditions., as all samples are introduced into the same bath,
the moving arm is driven by a micro processor controlled electronics to allow exact
30 strokes/minute oeration with automated re-adjustment at each stroke, while the
moving distance is pre-adjusted by means of an eccentric drive arm. A suitable
thermostat is used to program the testing temperature usually 36 to 38.0 C. A
digital timer can be programmed for the total testing time within a range of 10
seconds to 9 hours, 59 minutes and 59 seconds.
2.16.5 Spectrophotometry:
Spectrophotometry is the quantitative study of electromagnetic spectra. It
is more specific than the general term electromagnetic spectroscopy in that
spectrophotometry (DRU-400) deals with visible light, near ultraviolet, and near
infrared. Spectrophotometry involves the use of a spectrophotometer. A
spectrophotometer is a photometer (a device for measuring light intensity) that can
measure intensity as a function of the color, or more specifically, the wavelength of
light.
Here are two major classes of spectrophotometers; single beam and double
beam. A double beam spectrophotometer measures the ratio of the light intensity
on two different light paths, and a single beam spectrophotometer measures the
absolute light intensity. Although ratio measurements are easier, and generally
stabler, single beam instruments have advantages; for instance, they can have a
larger dynamic range, and they can be more compact.
Figure: Spectrophotometer
• Nebulizer:
*Acquire liquid sample at a controlled rate
*Create a fine aerosol for introduction into the flame
*Mix the aerosol and fuel and oxidant thoroughly for introduction
into the flame
• Flame:
*Destroy any analyte ions and breakdown complexes
*Create atoms (the elemental form) of the element of interest Fe0,
Cu0, Zn0, etc.
• Monochromator:
*Isolate analytical lines' photons passing through the flame
*Remove scattered light of other wavelengths from the flame .In
doing this, only a narrow spectral line impinges on the PMT.
Here water was used for all dissolution study.10 ml of dissolution fluid was
withdrawn at a predetermined time interval and water was added after the
dissolution fluid withdrawn. The total duration of dissolution study was 60 mins.
2.18 Reagents:
A reagent is a substance consumed during a chemical reaction. Although
they are involved in the reaction, are usually not referred to as reactants. Reagent is
often used in a more specialized sense as "a test substance that is added to a
system in order to bring about a reaction or to see whether a reaction occurs"
-Water.
-Ibuprofen tablet
3.1. Results of Physical Tests of Tablets:
Table: 3.1.General Appearance:
A 3.26±0.013
B-1 3.57±0.020
B-2 3.37±0.026
B-3 4.39±0.045
B-4 3.41±0.007
B-5 2.91±0.011
A 97.4±4.193
B-1 83.2±3.493
B-2 116.4±8.645
B-3 90.4±2.148
B-4 70.5±0.492
B-5 55.2±4.258
B PERCENATGE OF REMARKS
RAN FRIABILITY OF EACH
D BRAND
A 0.1 % Passed
B-1 0.4 % Passed
B-2 0.4 % Passed
B-3 0.6 % Passed
B-4 0.3 % Passed
B-5 0.3 % Passed
The disintegration time of each sample from each brand was expressed in
minutes (min). The Results for disintegration test for all the samples are
summarized below:
TABLE 3.6: RESUTLS OF DISINTEGRATION TEST DIFFERENT BATCHES
UNDER INVESTIGATION
in 900
Time(min) absorbance Conc.(µg/mL) conc. in 10 mL mL %release
Time(min) % release
0 0
30 74.35
45 87.37
60 91.14
Sample A
100
80
%release
60
%release
40
20
0
0 20 40 60 80
Time
The above chart and figure gives the idea about the sequential release of the drug
at those withdrawal times. The release of Ibuprofen at 60 minutes maintains the
specification according to British Pharmacopoeia.
Time(min) %release
0 0
30 73.73
45 76.26
60 78.27
Graphical representation of time vs. % release of: B-1
Sample B-1
90
80
70
60
%release
50
%release
40
30
20
10
0
0 20 40 60 80
time
Time(min) %release
0 0
30 73.09
45 76.07
60 80.16
Sample B-2
90
80
70
60
%release
50
%release
40
30
20
10
0
0 20 40 60 80
time
The above chart and figure gives the idea about the sequential release of the drug
at those withdrawal times. The release of Ibuprofen at 60 minutes maintains the
specification according to British Pharmacopoeia.
Time(min) %release
0 0
30 78.9
45 82.82
60 86.12
Sample B-3
100
80
%release
60
%release
40
20
0
0 20 40 60 80
Time
The above chart and figure gives the idea about the sequential release of the drug
at those withdrawal times. The release of Ibuprofen at 60 minutes maintains the
specification according to British Pharmacopoeia.
Time(min) %release
0 0
30 76.07
45 78.9
60 92.39
Sample B-4
100
80
%release
60
%release
40
20
0
0 20 40 60 80
time
The above chart and figure gives the idea about the sequential release of the drug
at those withdrawal times. The release of Ibuprofen at 60 minutes maintains the
specification according to British Pharmacopoeia.
Time(min) %release
0 0
30 74.35
45 87.37
60 91.14
Sample B-5
100
80
%release
60
%release
40
20
0
0 20 40 60 80
time
The above chart and figure gives the idea about the sequential release of the drug
at those withdrawal times. The release of Ibuprofen at 60 minutes maintains the
specification according to British Pharmacopoeia.
B- B- B-
A %of B -1% B-2%of 3%of 4%of 5%of
releas of releas releas releas releas
Time(min) e release e e e e
0 0 0 0 0 0 0
100
90
80 A%of release
70 B-1% of release
%release
60
B-2 %of release
50
B-3% of release
40
30 B-4% of release
20 B-5% of release
10
0
0 20 40 60 80
Time
From the above table and the graphical representation it can be concluded that
the release profile of almost all the samples were complied with the specification.
No major difference between their release properties.
02 25 9.9 20 10.1
03 25 20.8 30.8 10
Then studied the release pattern of drug in dissolution apparatus with in distilled
water as dissolution media at a temperature of 37o±5oc at 50 RPM. For 60 minutes
and withdraw 10 ml sample at 30, 45, 60, minutes. The present release of
Ibuprofen was plotted against time to get the zero order plots. Zero order plots
show the reasonably straight line with high correlation coefficient value.
CONCLUSION
Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID), which
relieves pain and swelling (inflammation). It is used to treat headaches, muscle
aches, backaches, dental pain, menstrual cramps, arthritis, or athletic injuries. This
medication is also used to reduce fever and to relieve minor aches and pain due to
the common cold or flu. This drug works by blocking the enzyme in your body that
makes prostaglandins. Decreasing prostaglandins helps to reduce pain, swelling,
and fever.
In the prospect of the world demand for “OTC” drugs are increasing
day by day. Ibuprofen has huge demand for its anti-pyretic, analgesic effect and
also for its anti-inflammatory non- steroidal activity.