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J.N.V. Indira DeviM.Pharmacy 1st yearPharmaeutical analysisYalamarty pharmacy college
ANALYSIS OF ANALGESICS and
ANTIPYRETICS
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INTRODUCTION CLASSIFICATION MECHANISM OF ACTION:
AnalgesicsAntipyretics
METHOD OF ANALYSIS CONCLUSION REFERENCES
ANALGESICS
• Analgesics are a class of drugs used to relieve pain by selectively inhibiting the perception of the pain.
ANTIPYRETICS
•An antipyretic is a type of medication that
will reduce fever by lowering temperature
from a raised state.
They are available in the form of tablets,capsules,ointments,syrups and parentrals.
CLASSIFICATION OF ANALGESICS AND ANTIPYRETICS
SALICYLATES
Na.salicylate Benorilate:
ARYL ALKANOIC ACID/ARYL ACETIC ACID DERIVATIVES
Indomethacine sulindac
PHENYL ACETIC ACID/ PHENYL PROPIONIC ACID DERIVATIVES
Ibuprofen Diclofenac
PYRAZOLONES/PYRAZOLODIENES:
Antipyrin .Aminopyrine
PARA AMINO PHENOL DERIVATIVES
1.Paracetamol, 2.Acetophenetidin
QUINOLINE DERIVATIVES
Ex:1.Cinchophen, ,
2.NeoCinchophen
N-ARYL ANTHRANILIC ACID/FENAMATES
Ex: Mefenamic acid , Flufenamicacid
OXICAMS/ENOLIC ACIDS
Ex:Piroxicam,
Isooxicam
SELECTIVE COX2 INHIBITORS:
Ex: Etoricoxib
Rofecoxib
GOLD COMPOUNDS:
EX: Aurothioglucose, aurofin
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OTHER ANALGESICS
OpioidsAlpha–2 agonists Thiazine derivatives
LocalAnalgesics
•Morphine
•Oxymorphone
•Meperidine (demerol)•Methadone
•Xylazine
•Meditomidine (domitor)
•Lidocaine (xylocaine)• Benzocaine
NSAIDs
Prostaglandins
pGE2 pGF2
Nerve ending of pain
Pain
Bradykinin
histamine
factors
+
•Analgesic Mechanism block prostaglandins production• Site of action: peripheral tissue
ANALGESIC MECHANISM
NSAIDs
PyrogenProstaglandinspGE2
thermoregulatory center
heat production ↑Heat dissipation ↓
set point ↑
Fever
•Antipyretic MechanismBlock prostaglandins production •Site of actionCentralNervousSystem
ANTIPYRETIC MECHANISM
METHOD OF ANALYSIS
Aspirin Diclofenac sodium Aceclofenac Ibuprofen Paracetamol Analgin Antipyrine Indomethacine Mefenamic acid
Aspirin
Method of analysis
Tablet Limits : 95.0 -105.0 % of the stated amount of Aspirin
Uses:-Analgesic and antipyretic.-Anti rheumatic.-Anti gout.-Anti platelet agent.
Aspirin is 2-acetoxybenzoic acid.
1. Identification:0.5 g drug + 10 ml of sodium hydroxide solution 1.boil for 3 min add 10 ml of dil.sulphuric acid
2. cool white, crystalline precipitate is produced
add FeClз solution Filter, dissolve the precipitate in 2 ml of water
deep violet colour is produced.
2.Titrimetric analysisAssay of aspirin
.
Powdered 20 tablets
0.5 g of powder
equivalent drug taken
30.0 ml of 0.5 M NaoH added,gently
boiled
Titrated with 0.5 M HCl using
phenol red
Blank is performe
d
Equivalent factor:1ml of 0.5M HCl ≡ 0.04504g of aspirin
Amount of aspirin=(B.R-S.R) * volume of NaOH added *(Actual molarity of HCl) * E.F B.R Theoritical molarity of HCl B.R=blank readingS.R=sample reading
3.Chromatographic Method of AnalysisHigh performance liquid chromatography of aspirin
Column :C18 silica column (5-um particlesize) Length:25cm Inner diameter: 4.4 mm Flow rate: 1.5 ml/min. Mobile phase :Acetonitrile:Water(HPLC grade)=1:9 Injection volume: 10μl. The detector measures absorbance at 254 nm.
Sample Preparation Analgesic tablet was ground into a fine powder Weighed approximately 0.2502g and dissolved in 25 mL of HPLC solvent
with gentle heating in a100ml volumetric flask. Cooled to room temperature and diluted to volume with HPLC solvent. Five mL of the solution was diluted to 50 mLwith HPLC solvent in
a volumetric flask and injected in to HPLC.
Diclofenac sodium
Tablet Limits : 90%-110% of the stated amount of Diclofenac
Method of analysis
Also known as Voltaren Sodium
It ranks Second in sales (1983) world wide
IUPAC name:2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetic acid
Uses:-Analgesic and antipyretic.-In rheumatic fever.
1.Identification:
0.4 per cent w/v solution in methanol +1 ml of nitric acid dark red colour develops
Assay of diclofenac sodium
.
2..U.V spectrophotometric method
Reference solution : A 1 % w/v solution of diclofenac sodium RS in methanol
Calculate the content from the absorbance obtained.
Weigh and powder 20 tablets
50 mg of Diclofenac Sodium
Shake with 60 ml of methanol in a
200mL volumetric flask
Dilute to volume with methanol
Dilute 5.0 ml of this solution to 100 ml
with methanol
Measure the absorbance of the
resulting solution at 285 nm
3.Potentiometric method by Non-aqueous titrimetry
End point determined potentiometrically by plotting ∆pH/∆v on y-axis and volume of titrant added on x-axis.
Equivalent factor:1ml of 0.1M HClO4≡0.03181g of diclofenac sodium
Amount of drug = volume of titrant consumed * Actual molarity of HClO4 * E.F
Theoritical molarity of HClO4
0.2gm powder equivalent of diclofenac tablets+50ml glacial acetic acid
Titrate against 0.1M HCl04
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Aceclofenac
IUPAC Name:[(2,6-dichlorophenyl)amino]phenylacetoxyacetic acid.
Tablet Limits : 99%-110% of the stated amount of Aceclofenac
Uses:-Analgesic and antipyretic.-In rhemuatoid arhritis.
Method of analysis
1. Identification:
When examined in the range 220 nm to 370 nm ,the 0.002 per cent w/v solution in methanol shows an absorption maximum at 275 nm .
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2.Potentiometric nethod:
Powder 20 tablets,take 0.5g powder equivalent
aceclofenac
Dissolve in 40ml of
methanol
Titrate with 0.1M NaOH
Blank is performed.
End point is determined potentiometrically by plotting ∆pH/∆v on y-axis and volume of titrant added on x-axis.
Equivalent factor:1ml of 0.1M NaOH≡0.0354g of Aceclofenac
Amount of drug = volume of titrant consumed * Actual molarity of NaOH * E.F
Theoritical molarity of NaOH
Ibuprofen
Tablet Limits : 95%-105% of the stated amount of ibuprofen
Method of analysis1.Identification:
Thin-layer chromatography coating the plate with silica gel H.Mobile phase: 75 volumes of n-hexane, 25 volumes of ethyl acetate and 5 volumes of glacial acetic acid.Test solution: 0.5 g of the substance under examination in 100 ml of dichloromethane.Reference solution. A 0.5 per cent w/v solution of ibuprofen RS in dichloromethane.Procedure:• Apply to the plate 5 μl of each solution. • After development, dry the plate at 120° for 30 minutes• Lightly spray the plate with a 1 per cent w/v solution of potassium permanganate in 1 M sulphuric acid.• Heat at 120° for 20 minutes and examine in ultraviolet light at 365 nm.The principal spot in thechromatogram obtained with the test solution corresponds to that in the
chromatogram obtained with the reference solution.
IUPAC name:2-[4-(2-methylpropyl)phenyl]propanoic acid
Uses:-Analgesic and antipyretic.-In rhemuatoid arhritis.-In spondilitis.
2.Titrimetric method Assay of ibuprofen
.
Equivalent factor:1ml of 0.1N NaoH≡0.02063g of ibuprofen.
Amount of ibuprofen=vol. of NaOH consumed * Actual normality * E.F
Theoritical normality
3.U.V spectrophotometric methodSolvent: Chloroform
Wave length:264 nm
So, Ibuprofen present in bulk samples can be estimated
Take 0.2g powder
equivalent drug
Extract with 25mL portions of ether and
evaporate the combined ether
layer
Dissolve the entire
residue in 100ml
methanol
Titrate with 0.1N NaoH
using phenol red
Paracetamol
IUPAC name: N-(4-hydroxyphenyl) acetamide
Uses:-Analgesic and antipyretic.
Method of analysis1.Identification0.1 g drug + 1 ml of hydrochloric acid boil 3 minutes add 10 ml of water and cool
no precipitate is produced
Add 0.05 ml of 0.0167 M potassium dichromate
violet colourdevelops which does not turn red.
Reagents:1%w/v 2,4-dinitrobenzaldehyde in 5% v/v 0.1N H₂SO4,1N HCl
The schiff’s base measured at 435nm
2. Colorimetric method:a)With 2,4-DNB
Yellow colour
Reagents:
0.1%w/v solution of sodium nitrite in water.
0.5%w/v solution of ammonium sulpha mate in water
0.1%w/v solution of N-1-napththyl ethylene di amine dihydrochloride
(NED) in water.
5N HCL
Procedure:
b)Diazotization with NED:
sample+1ml
of 5N HCl
1ml of NaNO2
soln.
mix well for
10min in
ice,below10°c
add 1ml of
ammonium
sulphamate
then add 1ml
of NED
reagent
Pink azodye is
formed
Absorbance
measured at
555nm.
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3.U.V spectrophotometric method :Assay
Calculate amount of paracetamol in tablets taking 715 as the specific absorbance at 257 nm.
Powder 20 tablets and Weigh accurately a
powder equivalent of 0.15g drug
add 50 ml of 0.1 M sodium hydroxide, dilute with 100 ml
water
shake for 15 minutes and add sufficient
water to produce 200.0 ml
Mix, filter and dilute 10.0 ml of the filtrate
to 100.0 ml with water
To 10.0 ml of the resulting solution add
10 ml of
0.1 M sodium hydroxide, dilute to 100.0 ml with water
and mix well
Measure the absorbance at 257 nm
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Thin Layer Chromatography Method for the Determination of Paracetamol and Ibuprofen in Pharmaceutical
Formulation
The purpose of this study to obtain an efficient solvent for extracting paracetamol and ibuprofen from sample and a good eluent for separation between paracetamol and ibuprofen on the TLC plate.
Adsorbant:Silica gel 60 GF 254 . Mobile phase:Ethylacetate : n-hexane, (75 : 25 v/v)
Retardation factor (Rf) :
Paracetamol: 0.24
Ibuprofen: 0.64 Resolution factor between paracetamol and ibuprofen was 6.4. The analyte spots were quantified using densitometry method :
Paracetamol:244 nm
Ibuprofen:260nm
Methods of analysis
1.Iodimetry method:Assay
1ml of 0.05 M iodine is equivalent to 0.01757 g of Analgin
Analgin
Weigh accurately
about 0.5g powder
equivalent of
analgin from 20
tablets
dissolve in a mixture
of 40 ml of ethanol
(95%) and 10 ml of
0.01M HCl shake and
filter
titrate 25 ml of filtrate
with 0.05 M iodine
until a yellow colour
stable for 30 sec. is
produced.
Reagents:0.5M Phthalate Buffer: pH:4.0
0.5%w/v 1,2-napthaquinone-4-sulfanic acid (NQS)-sodium
Procedure:
2ml of sample add 5ml of buffer + 1ml of NQS-sodium
heat on water
bath for 60°c for 40min
extract with chloroform
orange colour appears
absorbance measured at 475nm.
2. Colorimetry method:
Method of analysis:
1.Gravimetric method
2.Colorimetric methods
3.Polarographic methodIUPAC Name:1,5-dimethyl-2-phenyl-2,3-dihydro-1H-
pyrazol-3-one
Antipyrine
Uses:-An analgesic and antipyretic that has been given orally and as ear drops. -Used in testing the effects of other drugs or diseases on drug-metabolizing enzymes in the liver.
1. Gravimetric method
The precipitate is weighed to determine the weight of antipyrine present.
In a sodium
bicarbonate solution,
antipyrine + iodine is
added
mono iodo addition
compound
extracted into chloroform
+sulphur dioxide
Iodine released, silver
nitrate is addedsilver iodide is pptd.
REAGENT SOLUTION: P-di methyl amino benzaldehyde (0.5g)
is dissolved in a mixture of 4.5ml of concentrated sulphuric
acid and 8.5ml of water.
2.Colorimetric method
PDAB
ANTIPYRINE Absorbance measured at 513nm.
Rose red to Salmon pink complex
Antipyrine is nitrosated to give a compound which is
reducible at the dropping mercury electrode.
Procedure:
3. Polarographic method
1 ml of 0.1N H2SO4 and 1ml of
0.1N NaNO2are added to 1ml of
approximately 10-2 M
antipyrine
The mixture is allowed to
stand for 12min at 23°C to
28°C, to ensure complete
reaction
Excess HNO2 is neutralized
with 1ml of 0.1N NaOH
0.5ml of 1%gelatin solution
is added, and the solution is
polarographed.
Concn. is reported to be
proportional to the diffusion
current.
Mefenamic acid
IUPAC Name: 2-[(2,3-dimethylphenyl)amino]benzoic acid
1. Identification:5 mg drug in 2 ml of sulphuric acid + 0.05 ml of 0.0167 M potassium dichromate
intense blue colour isproduced immediately which fades rapidly to brownish-green.
Method of analysis:
Test solution: Weigh 20 capsules 50 mg equivalent Mefenamic acid
250 ml volumetric flask Add 5 ml of tetrahydrofuran Shake for 10 minutes with the aid of ultrasound
Dilute with mobile phase & filter
Reference solution: A solution containing 0.02 % w/v of mefenamic acid RS in the mobile phase.
2.Liquid chromatography:Assay
Mobile phase: a mixture of 23 volumes acetonitrile,20 volumes of 0.05 M of monobasic ammonium phosphate adjusted to a pH of 5.0 with 3 M ammonia and 7 volumes of THF
_ flow rate. 1 ml per minute– spectrophotometer set at 254 nm– a 20 μl loop injector_Inject alternately the test and the reference solution.Calculate the content of C15H15NO2 in the capsules.
Indomethacin
IUPAC Name 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetic acid
Methods of analysis1.Identification: Dissolve 0.1 g in 10 ml of ethanol (95 per cent), heating gently if necessary
To 0.1 ml add 2 ml of a freshly prepared mixture of 1 volume of a 25 per cent w/v solution ofhydroxylamine hydrochloride and 3 volumes of 2 M sodium hydroxide. Add 2 ml of 2 M hydrochloric acid and 1 ml of ferric chloride solution and mix
violet-pink colour develops.
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2.U.V spectrophotometric method :Assay
Weigh accurately 20 capsules
50mg equivalent of Indomethacin
Add 10 ml of water and allow to stand for 10 min,
with occasional swirling.
Add 75 ml of methanol, shake well,
Add sufficient methanol to produce 100.0 ml and filter if necessary.
To 5.0 ml of the filtrate add sufficient of a mixture of equal volumes of methanol and phosphate buffer pH 7.2 to produce 100.0 ml.
Measure the absorbance of the resulting solution at the maximum at about 320 nm
Calculate the content of indomethacin taking 193 as the specific absorbance at 320 nm.
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•High Performance Thin Layer Chromatographic Analysis of Paracetamol and Etodolac in Combined Tablet Dosage Form.
•Quantitative Analysis of Antipyretics and Analgesics in Solid Dosage Forms by Powder X.Ray -Diffraction.
•Analytical method development and validation of Piroxicam by RP-HPLC.
•Simultaneous estimation of nimesulide and paracetamol in marketed formulation by uv-spectroscopy
Recent method of analysis
CONCLUSION
I here by conclude that there is a much necessity for the study of analytical methods of Analgesics and Antipyretics as they are widely used class of drugs…
REFERENCES
• The Indian Pharmacopeia volume( ii) 2007
Analgin page numbers : 117-118 Aspirin page numbers: 127-128
Aceclofenac page numbers: 62-63
• Pharmaceutical Analysis Book: Takeru Higuchi. A.S.Doniger Kenneth A.
Connors Antipyrine : (557-559),
Amino pyrine: (559-561)
• P. D. Sethi, “Quantitative Analysis of Drugs in Pharmaceutical Formulations”,.
• B. Morelli, J. Pharm. Biomed. Anal.,1989, 7, 577.
• http://analgesics and antipyretics.cwru.edu/encycl/.com
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