International Journal of Pharmacy and Pharmaceutical Sciences

ISSN- 0975-1491

Vol 3, Suppl 3, 2011

ResearchArticle

SPECTROPHOTOMETRICSIMULTANEOUSANALYSISOFPARACETAMOL,PROPYPHENAZONE
ANDCAFFEINEINTABLETDOSAGEFORMS

KULDEEPDELVADIYA,RITUKIMBAHUNE,PRACHIKABRA*,SUNILK,PRATIKPATEL
DepartmentofQualityAssurance,NargundCollegeofPharmacy,Dattatreyanagar,IIMain,100Ft.RingRoad,BSKIIIStage,Bangalore
560085,India.Email:prachi.v.kabra@gmail.com
Received:01March2011,RevisedandAccepted:03April2011
ABSTRACT
Inthisproposedstudy,thesimultaneousanalysisofParacetamol,PropyphenazoneandCaffeinebyUVVisiblespectrophotometryintheirternary
mixtureandintabletdosageformisbasedontheadditivityofabsorbanceofthedrugs.Theabsorptionmaximaofdrugswerefoundtobeat243nm
for paracetamol, 266 nm for propyphenazone and 272.8 nm for caffeine in double distilled water and these wavelengths were selected for the
analysis.ParacetamolobeyedBeerLambertslawintheconcentrationrange of216 g/mlat243nm,440g/mlat266nmand660g/mlat
272.8nm,whereaspropyphenazonewasobservedtobelinearintheconcentrationrangeof220g/mlatallthreeselectedwavelengths.Caffeine
wasfoundtobelinearintheconcentrationrangeof220g/mlat272.8and266nmand1070g/mlat243nm.Thestandardabsorptivityvalues
werecalculatedateachwavelengthandtheamountofdrugsinthetabletdosageformwerecalculatedbysolvingmatrixusingCramersrule.This
proposedmethodwasstatisticallyvalidatedinaccordancewithICHguidelines.Precisionwascalculatedasinterdayandintradayvariationsofthe
drugabsorption.Thereproducibility,repeatabilityoftheproposedmethodwerefoundtobesatisfactorywhichwasevidencedbylowvaluesofRSD
(<5%). Recovery ofthe developed method was found to be in the range of 95102%. This method can be applied successfully for the routine
analysisofParacetamol,PropyphenazoneandCaffeineanalgesic,antipyretictabletsinpharmaceuticalindustry.
Keywords:Paracetamol,Propyphenazone,Caffeine,Cramersrule,Matrix

INTRODUCTION

MATERIALSANDMETHODS

Tablets containing Paracetamol (PCM), Propyphenazone (PP) and

Caffeine (CAF) are emerging as the most widely prescribed
combination for pain relief1,2. PCM, PP and CAF in combination
causesreductionintheamountofprostaglandinwhereasCAFisalso
known to increase the analgesic effect of PCM and PP,
synergistically, providing relief from symptoms like headache,
muscular aches, neuralgia, backache, joint pain, rheumatic pain,
migraine, general pain, toothache and menstrual pain. The
combination is also found to be effective in controlling fever
originatingfrombacterialorviralinfection.Withlimitedsideeffects
thecombinationissuitableforallages3.

Instrumentation

PCMis4hydroxyacetanilide,sparinglysolubleinwaterandPP isa
4isopropyl2, 3dimethyl1phenyl3pyrazolin5one, slightly
solubleinwaterwhereasacentralnervoussystemstimulant,CAFis
3, 7dihydro1, 3, 7trimethyl1Hpurine2, 6dione, sparingly
solubleinwater4(Fig.1).

Experimental

AShimadzuUVVisiblespectrophotometermodel1700(Japan)with1
cm matched quartz cells was used along with a Sartorius digital
balance.
Chemicalsandreagents
PCM,PPandCAFwerekindlysuppliedbyJuggatPharma,Bangalore,
India. Tablets containing PCM (300 mg), PP (150 mg) and CAF (50
mg)(Darttablets,JuggatPharma,Bangalore)wereusedasmarketed
formulation. Freshly prepared double distilled water was used
throughouttheexperiment.

Preparationofstandardstocksolution
StandardstocksolutionofPCMwaspreparedbydissolving100mg
PCMindoubledistilledwater,sonicatedfor10minutesandmadeup
thevolumeupto100mlwhereasstandardstocksolutionofPPand
CAF were prepared by dissolving 10 mg in double distilled water,
sonicatedfor10minutesandmadeupthevolumeupto100ml.
Determinationofwavelengthofmaximumabsorbance

Paracetamol PropyphenazoneCaffeine
Fig.1:Structureofdrugs.
Currently, the reported methods for simultaneous estimation of
PCM,PPand CAFincombined dosageformaresingleflowthrough
UV multiparameter sensor5, derivative ratio spectrazero crossing
spectrophotometry6 and HPLC methods7. Despite being a popular
combination, there are no simple simultaneous UVVisible
spectrophotometricmethodsreported.
This study proposes a simple, rapid, accurate and cost effective
simultaneous spectrophotometric analysis for the estimation of
PCM,PPandCAFincombineddosageforms.

The stock solutions of PCM, PP and CAF were further diluted with
double distilled water to get concentration of 30 g/ml. This
solutionwasscannedintherange200400nm.Thewavelengthsof
maximumabsorbanceofPCM,PPandCAFwerefoundtobeat243,
266and272.8nmrespectively(Fig.2).
Preparationofcalibrationcurve
ThestocksolutionofPCMwasappropriatelydilutedwithdouble
distilledwatertoobtainconcentrationrangeof216g/ml,440
g/mland660g/mlandweremeasuredat243,266and272.8nm
respectively(Fig.3).
The stock solution of PP was appropriately diluted to obtain
concentration range of 220 g/ml with double distilled water and
measuredat266,243and272.8nm(Fig.4).
The stock solution of CAF was appropriately diluted to obtain
concentrationrangeof220g/mlandabsorbanceofthesolutions
were measured at 272.8 and 266 nm whereas this stock solution
was also diluted to 1070 g/ml with double distilled water and
absorbanceweremeasuredat243nm(Fig.5).

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Fig.2:OverlainspectraPCM,PPandCAFindoubledistilledwater

Fig.3:CalibrationcurveforPCMat243,266and272.8nm.

Fig.4:CalibrationcurveforPPat266,243and272.8nm
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IntJPharmPharmSci,Vol3,Suppl3,2011,170174

Fig.5:CalibrationcurveforCAFat272.8,266and243nm.

Assayofmarketedformulation
Twentytabletswereweighedandcrushedtoafinepowder.Powder
equivalent to 60 mg of PCM, 30 mg of PP and 10 mg of CAF was
accurately weighed and transferred in a 100 ml volumetric flask.
Approximately 20 ml of double distilled water was added and
sonicated for 15 minutesandthenvolume was made upto 100ml

withdoubledistilledwater.Insolubleexcipientswereseparatedby
filtrationusingwhatmanfilterpaperno.41.
Thefiltratewasfurtherdilutedtogetfinalconcentrationof6,3and
1g/mlofPCM,PPandCAFrespectively.Absorbancewasmeasured
atthreeselectedwavelengthsandconcentrationsweredeterminedby
solvingmatrixbyusingaCramersruleandresultsshowninTable1.

Table1:Resultsoftheassayofmarketedtablets
Drug

Labelclaim
mg/tab
300
150
50

PCM
PP
CAF

MeanAmountfound
(mg/tab)
305
145
53

MeanAmountfound
(%)
101.66
101.65
106

R.S.D.(%)n=3
1.6868
3.275
4.2316

Table2:Resultsofrecoverystudies

Drug
PCM
PP
CAF

50%Addition
99.891.7713
98.660.9555
95.221.4682

Percentofamountofthedrugfoundinpreanalysedtabletpowder(n=3)
100%Addition
150%Addition
100.390.4752
99.710.7742
98.440.6931
100.301.2043
102.831.9490
102.072.5795

RESULTS

DISCUSSION

Methodvalidation

Tostartwith,theoverlainspectraofPCM,PPandCAFwerestudied
in traditional solvents like 0.1N sodium hydroxide, 0.1N
hydrochloric acid, methanol, ethanol, dimethyl formamide and
doubledistilledwater.ExceptforminordifferencesinPPspectrum
in water, the overlain spectra of PCM and CAF were found to be
almost identical due to which it was not feasible to analyse the
mixture byusing traditional simultaneous equation and absorption
ratio method. As a result, it was concluded that double distilled
waterwasthebestsuitedforthis studyasit offeredadvantagesof
common solubility and lower cost of analysis over the above
solvents. All the three drugs absorb at each others wavelength of
maximumabsorbance.Anabsorbanceofmixtureateachwavelength
is the combined absorbance of all the drugs. By applying the Beer
Lambert's equation (A=abc when pathlength is 1 cm, A=ac), the
absorbanceofmixtureateachwavelengthisderivedasfollows.

Precision
Theprecisionofthemethodwasdeterminedbyrepeatability(intra
day) and intermediate precision (interday) and expressed as
relativestandarddeviation(RSD).Intradayprecisionwasevaluated
by analysis of three concentration levels in triplicate of all drugs
(For PCM 2,8,16 g/ml,PP and CAF 2, 10, 20 g/ml) at three
differenttimeintervalsunderthesameexperimentalconditionson
the same day. Intermediate precision (interday precision) was
determined by analysing above mentioned concentrations of each
drugintriplicateonthreeconsecutivedays.
Recoverystudies
To study the accuracy of the proposed method, recovery studies
were carried out by standard addition of drug at three different
levels(50%,100%and150%).AknownamountofPCM,PPandCAF
wereaddedtopreanalysedtabletpowderandpercentagerecovery
of each drug was calculated. The results of recovery studies are
presentedinTable2.

a1Cx+b1Cy+c1Cz=A1at1(243,maxofPCM)
a2Cx+b2Cy+c2Cz=A2at2(266,maxofPP)
a3Cx+b3Cy+c3Cz=A3at3(272.8,maxofCAF)
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A1,A2andA3aretheabsorptionsofthemixtureofthedrugsat1,2
and 3respectivelywhereCx,CyandCzindicatestheconcentration
of PCM, PP and CAF. In the above matrix, a1, a2 and a3 are the
absorptivityofPCM,b1,b2andb3aretheabsorptivityofPPandc1,c2
andc3aretheabsorptivityofCAFat1,2and3respectively.
Absorptivityofallthedrugsatallthewavelengthswasdetermined
from the calibration curves and above equations is derived as
follows:
659Cx+236Cy+149Cz=A1....(1)
392Cx+405Cy+375Cz=A2.(2)
143Cx+426Cy+518Cz=A3.(3)
Since the above equations have 3 unknowns, Matrix methodology
was used as it easily solves the system of equations with three
unknowns.Theabove3equationsweredrawninamatrixformand
thenCramersRulewasusedtosolvethematrix.Theresultwasthe
concentrationofPCM,PPandCAFinthesamplesolution.
ItwasnoticedthatalldrugsobeytheBeerLambertslawindifferent
concentration range and the range of concentration was selected
factoring the relative error. Precision was calculated as interday
and intraday variations of drug absorption. The reproducibility,
repeatabilityoftheproposedmethodwerefoundtobesatisfactory
whichwasevidencedbylowvaluesofRSD(<5%)showninTable3.
Recovery ofthe developed method was found to be in the range of

95102%.Theuncoatedtablets containing 300mgofPCM,150mg

of PP and 50 mg of CAF (DART Tablets) were analysed (n=6), the
amount of drugs were found to be satisfactory and in the limits of
officialpharmacopoeia.
Thestudyestablishedthatbyadoptingthismethod,thetimetaken
for analysis can be reduced as this method involves very limited
steps when compared to the traditional methods. While in the
traditionalmethod,thePCM,PPandCAFwereneedtobeseparated
before analysis,byadoptingthe proposedmethodologythe sample
solution of tablets was needs to be prepared as per the assay
procedureandmeasuredat243,266and272.8nm.Matricesshould
bedrawnusingthevaluesofabsorptionofthesamplesolution and
then solved using Cramer's rule to determine the amount of each
drug in the sample solution. Results of all validation aspects are
showninTable3.
Thus the developed spectrophotometric method in the present
investigationwasfoundtobesimple,sensitive,accurateandprecise
and can be successfully applied for the routine analysis of
Paracetamol,PropyphenazoneandCaffeineintabletdosageform.
ACKNOWLEDGEMENT
TheauthorsshallremaingratefultoJuggatPharmaLtd.,Bangalore,
IndiaforprovidingPCM,PPandCAFintheformofGiftsampleand
Nargund College of Pharmacy, Bangalore, for providing lab and
researchfacilitiestocompletethiswork.

Table3:Analyticalvalidationparameters
Drugsname
PCM

Parameters
Wavelengths(nm)
Beerslawrange(g/ml)
Standardregressionequations(n=9)
Standardabsorbancevalue,
A[1%,1cm]
CorrelationCoefficient
LOD(g/ml)
LOQ(g/ml)
Wavelengths(nm)
Beerslawrange(g/ml)
Standardregressionequations(n=9)

PP

Standardabsorbancevalue,
A[1%,1cm]
CorrelationCoefficient
LOD(g/ml)
LOQ(g/ml)
Wavelengths(nm)
Beerslawrange(g/ml)
Standardregressionequations(n=9)

CAF

Standardabsorbancevalue,
A[1%,1cm]
CorrelationCoefficient
LOD(g/ml)
LOQ(g/ml)

Observations
243
216
Y=0.065863x+
0.007256
658.6~659

266
440
Y=0.023599x
0.000289
235.99~236

272.8
660
Y=0.014939x
0.003920
149.39~149

0.999630
0.092152
0.279249
243
220
Y=0.039220x
0.003645
392.20~392

0.999844
0.299317
0.907022
272.8
220
Y=0.037518x
0.000245
375.18~375

517.88~518

0.999310
0.093312

0.282764
266
220
Y=0.042631x+
0.009640
426.31~426

0.999431
0.076963

0.233221
243
1070
Y=0.01432x+
0.004106
143.2~143

0.9997
0.076657
0.232293

0.999670
0.132136
0.400413

0.999633
0.594092
1.800279

0.9997
0.131623
0.398858
266
220
Y=0.040459x0.001091
404.59~405
0.9996
0.050896

0.15423
272.8
220
Y=0.051788x+0.007601

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