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Presented by…

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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