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Methods of estimation of multi-component formulations: A review

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Mr. S.J. Daharwal

As the mankind made his way through remote times and places, he was always followed by

disease and sickness from ill health. Thus originated drugs and medicines to cure it and began

evaluation of practice of pharmacy and pharmaceuticals.

Market is flooded with combination of drugs in various dosage forms1 (Table-1). The multi-

components formulations have gained a lot of importance nowadays due to greater patient

acceptability, increased potency, multiple action, fewer side effects and quicker relief 2.

There is a plethora of analysis of such formulations without prior separation. For the estimation

of multi-component formulation, the instrumental techniques, which are commonly employed,

are spectrophotometry, GLC, high performance thin layer chromatography (HPTLC), HPLC etc.

These methods are based upon the measurement of specific and nonspecific physical

properties of the substances.

Spectrophotometric multi-component analysis

Absorption spectroscopy is one of the most useful and widely used tools available to the

analyte for quantitative analysis. The relation between the concentration of analyte and the

amount of light absorbed is the basis of most analytical applications of molecular

spectroscopy. This method of analysis is gaining importance due to simple, rapid, precise,

highly accurate and less time consuming. Spectrophotometric multi-component analysis can

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be applied where the spectra of drugs overlaps. In such cases of overlapping spectra,

simultaneous equation can be framed to obtain the concentration of individual component;

otherwise multi-component analysis can be applied on any degree of spectral overlap provided

that two or more spectra are not similar exactly. Some examples are listed in table-2.

The various spectroscopic techniques used for multi-component analysis are as

follows

Simultaneous equation method (Vierodt’s method) 3

Concentration of several components present in the same mixture can be determined by

solving a set of simultaneous equation even if their spectra overlap. If Beer’s law is followed,

these equations are linier.

Two wavelength method3

The method can be used to calculate the concentration of component of interest found in a

mixture containing it along some unwanted interfering component. The absorption different

between two points on the mixture spectra is directly proportional to the concentration of the

component to be determined irrespective of the interfering component.

The absorption ratio method3

The absorbance ratio method is a modification of the simultaneous equation procedure. It

depends on the property that for a substance, which obeys Beer’s law at all wavelength, the

ratio of absorbance at any two wavelengths is constant value independent of concentration or

path length. e.g. Two dilutions of the same substance give the same absorbance ratio A1 / A2.

In the USP, this ratio is referred to as Q value. In the quantitative assay of two components in

admixture by the absorbance ratio method, absorbances are measured at two wavelengths.

One being the λ max of one of the components (λ2) and the other being a wavelength of equal

absorptivity of the two components (λ1), i.e., an iso-absorptive point.

Geometric correction method3

A number of the mathematical correction procedures have been developed which reduce or

eliminate the background irrelevant absorption that may be present in the samples of

biological origin. The simplest of this procedure is the three-point geometric procedure, which

may be applied if the irrelevant absorption is linier at the three wavelengths selected. This

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procedure is simply algebraic calculations of what the baseline technique in infrared

spectrophotometry dose graphically.

Absorption factor method (Absorption correction method) 3

It is further modification of simultaneous equation method. Quantitative determination of one

drug is carried out by E (1%, 1 cm) value and quantitation of another drug is carried out by

subtraction absorption due to interfering drug using absorption factors.

Orthogonal polynomial method3

The technique of orthogonal polynomials is another mathematical correction procedure, which

involves complex calculation than the three-point correction procedure. The basis of the

method is that an absorption spectrum may be represented in terms of orthogonal functions.

Difference spectrophotometry3

Difference spectrophotometry provides a sensitive method for detecting small changes in the

environment of a chromophore or it can be used to demonstrate ionization of a chromophore

leading to identification and quantitation of various components in mixture. The essential

feature of difference spectrophotometric assay is that the measured value is the difference

absorbance (∆A) between two equimolar solutions of the analyte in different chemical forms,

which exhibits different spectral characteristics.

Derivative spectrophotometry3

Derivative spectrophotometry is useful means of resolving two overlapping spectra and

eliminating matrix interference due to an indistinct shoulder on side of an absorption bands. It

involves conversion of normal spectrum [A= f (λ)]to its first [dA/ dλ = f (λ)], second [d2A/ dλ2 =

f (λ)]and higher derivatives spectra where the amplitude in the derivative spectrum is

proportional to the concentration of the analyte provided that Beer’s law is obeyed by the

fundamental spectrum.

Area under curve method4

In this method, the absorptivity values (ε1 and ε2) of each of the two drugs were determined at

the selected wavelength range. Total area under curve of a mixture at wavelength range is

equal to the sum of area under the individual component at that wavelength range. This

method is applicable when the λ max of the two components are reasonably dissimilar, the two

components do not interact chemically and both the component must be soluble in same

solvent.

The methods deviated when overlapping of UV spectra of two drugs significantly and large

difference in labeled strength5. e. g. Tizanidine HCl 3.0 mg and nimesulide 100.0 mg per tablet.

The accuracy of the method depends upon nature of solvent, pH of solution, temperature, high

electrolyte concentration and the presence of interfering substances.

High performance liquid chromatography (HPLC):

This technique is based on the same method of separation as classical column

chromatography. i.e. adsorption, partition, ion exchange and gel permeation but it differ from

column chromatography, in that mobile phase is pumped through the packed column under

high pressure. The technique is most widely used for all the analytical separation technique

due to its sensitivity, its ready adaptability to accumulate quantitative determinations, its

suitability for separating nonvolatile species or thermally fragile ones. In normal HPLC, polar

solids such as silica gel; alumina (Al2O3) or porous glass beads and non-polar mobile phase

such as heptane, octane or chloroform are used but if the opposite case holds, it is called as

reversed phase HPLC. Some examples are listed in table-3 and 4

High performance thin layer chromatography (HPTLC):

The principle is based on plane chromatography. The mobile phase normally is driven by

capillary action. The prominent advantages of this technique includes possibilities of

separating of up to 70 samples and standard simultaneously on a single plate leading to high

throughout, low cost analogs and the ability to construct calibration curves from standard

chromatography under the same condition as the sample. Analyzing a sample by use of

multiple separation steps and static post chromatographic detection procedures with various

universal and specific visualization regents that are possible because all the sample

components are stored on the layer without the chance of loss. Some examples are listed in

table-5.

Gas chromatography (GC):

GC is one of the most extensively used separation technique in which separation is

accomplished by partitioning solute between a mobile gas phase and stationary phase, either

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liquid or solid. The chief requirement is same degrees of stability at the temperature necessary

to maintain the substance in gas state. Some examples are listed in table-6.

Validation of methods6:

Validation by definition is an act of providing that any process, method, equipment, material,

activity, system or analyst performs as expected under given set of conditions. When extended

to an analytical procedure, depending upon the application it means that a method works

reproducibility when carried out by a same or different person, in same or different

laboratories, using different regent, different equipment etc. It will ensure commitment to

quality of products and services. It builds a degree of confidence not only for the developer but

also to the user.

Validation of analytical method should follow a well documented procedure beginning with the

definition of the scope of the method and its validation criteria and including the compounds

and matrices, desired detection and quantitation limits and any other important performance

criteria. The scope of method should include different equipment and locations where the

method will be run. The methods were validated in terms of linearity, accuracy, precision,

specificity and reproducibility of sample applications. Analytical method validation has been

performed according to ICH guidelines. Accuracy of the method is certain on the basis of

recovery studies performed by the standard addition method. The formula used for calculating

recovery of pure drug is

Percentage recovery = T - A X 100 / S

Where T = Total amount of drug estimated

A= Amount contributed by formulation

S = Amount of pure drug added.

Precision of analytical method is expressed as SD and RSD of series of measurement by

replicate estimation of drug.

The stability indicating ability of the method has been investigated by deliberately degrading

the sample preparation. The stress conditions applied are acidic (0.1 M HCl), alkalis (0.1M

NaOH) and mild oxidizing condition (3% H2O2) for 24 hr at 50 C. Also heat (60C) and U.V.

exposure for 24 hr will be carried out on the sample.

The linearity of the method was investigated by serially diluting the stock solutions of drugs

and measured values.

Ruggedness studies has been carried out for different parameters i.e. days and analysts. The

results shall be compared with the method.

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Conclusion:

The multi-drug therapy is an ancient phenomenon to combat interrelated symptoms of

diseased status of human beings. Since it ensure timely and complete medication for disorder

and it has patient compliance, as it reduces the number of formulations to be taken at a time.

Therefore, the pharmaceutical formulations with combinations of drugs have shown an

increasing trend to counteract other symptoms specific to one drug n formulation, and hence

analytical chemist will have to accept the challenge of developing reliable methods for analysis

of drugs in such formulation.

Simultaneous analysis procedures are now being used more frequently for estimation of drugs

in multi-component pharmaceutical formulations due to their inherent advantages viz. avoid

time consuming extraction and separation, economical in the sense that use of expensive

regents is minimized are equally accurate and precise. . For the estimation of multi-component

formulation, the instrumental techniques, which are commonly employed, are

spectrophotometery, GLC, high performance thin layer chromatography (HPTLC), HPLC etc.

The validation of methods has to validate by using same parameters as per ICH guidelines.

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84. Trivedi P. and Gangwal S.; ‘Analysis of multicomponent formulation containing noscopine,

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36(1), 55-59.

85. Mahadik K. R. and Panzade P. D.;’ Simultaneous estimation of oflaxacine and tinidazole in

tablet dosage form’; Indian Drugs, 2001, 38(7), 368-370.

86. Kakade R. B.; Dhurvey Y. R. ; Gedam S. N.; Meghal S. K. and Kasture A. P.; ‘Simultaneous

estimation of pantoprozole and domperidone in pharmaceutical preparation by

spectrophotometric method’; Through 55th Indian Pharmaceutical Congress Scientific Abstract,

2003/ G-28.

87. Mundhe D. and Kaskhedikar S. G.; ‘Simultaneous estimation of paracetamol and

chlorzaxasone in tablet formulation’; East. Pharm., 1995, 38(452), 181-182.

88. Vasta D. K.; Rao G. J.; Ibrahim M.; Mannan A. and Karunasri G.; ‘Determination of

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103-104.

89. Mannan A.; et al; ‘Development of simultaneous estimation of paracetamol and

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90. Mahadik K. R. and Panzade P. D.;’ Simultaneous estimation of pefloxacine and

metrinidazole in tablet dosage form’; East. Pharm., 2000, 43(516), 115-116.

91. Panda S. K.; Sharma A. K.; and Sahu L. K.; ‘Simultaneous analysis of phynyl

propanalamine, chlorphenaramine and Bromohexine HCl in syrup by derivative

spectrophotometer’; Indian J. Pharm. Sci., 2002, 64(6), 540-544.

92. Sahu A. K. and Sahu L. K.; ‘Simultaneous spectrophotometric analysis of phynyl

propanalamine, chlorphenaramine malate and dextromethorphen hydrobromide in syrup ’;


93. Jain S. K.; Jain D.; Tiwari M. and Chaturvedi S. C.; ‘Simultaneous spectrophotometric

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94. Chaturvedi S.C.; Jain S. and Tiwari M.; ‘Propranolol HCl-diazepam- simultaneous estimation

by first order derivative spectroscopy’; Indian Drugs, 1998, 35(11), 696-699.

95. Kale V. M.; Talekar R. S. and Dhake A. S.; ‘‘Simultaneous determination of pseudo

ephedrine HCl and ibuprofen from combined dosage form by UV-spectrophotometer form’;

East. Pharm., 2000, 43(514), 115-118.

96. Trivedi P. and Gangwal S.; ‘Simultaneous analysis of pseudo ephedrine HCl, and

dextromethorphen hydrobromide from liquid oral dosage form’; Indian Drugs, 1999, 36(9),

568-571.

97. Trivedi P. and Sachan A.; ‘Simultaneous spectrophotometric determination of pseudo

ephedrine HCl, dextromethorphen hydrobromide and chlorphenaramine malate from multi

component liquid oral’; Indian Drugs, 1999, 36(7), 444-448.

98. Onar F.; Yuccsoy C.; Dermi S.; Kartal M. and Kokdil G.; ‘Simultaneous determination of

pseudo ephedrine sulphate, dexbrompheniramine melete and loratadine in pharmaceutical

preparation using derivative spectrometry and ratio spectra derivative spectrophotometry’;

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99. Sharma A. K. and Gangwal S.; ‘Simultaneous determination of pseudo mefanamic acid and

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100. J. J. Berzas Nevado; J. A. Murillio Pulgarin; J. Amador- Hernandez; M. A. Gomez

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101. Kuchekar B. S.; Thakar S. V.; Hirmath M. R.; Chothe P. P. and Shinde D. B.; ‘Simultaneous

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102. Goicocchee H. C. and Oliveri A. C.; ‘Simultaneous determination of rifampicin ,

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103. Rote A. R. and Sharma A. K.; ‘Spectrophotometric determination of rifampicin ,

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104. Rote A. R. and Sharma A. K.; ‘Simultaneous sectrophotometric determination of

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dosage form’; Indian J. Pharm. Sci., 1997, 59(3), 119-123.

105. Goyal P.; Pandey S. and Udupa N.; ‘Simultaneous spectrophotometric estimation of

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106. Manna A.; Ghosh I.; Sharmishtha D.; Ghosh P. K.; Ghosh L. K.; ‘Simultaneous estimation of

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107. Kasture A. V.; Wadodokar S. G. and Kakade R. B.; ‘Spectrophotometric determination of

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108. Manna A.; Ghosh I.; Datta S.; Gupta B. K.; Ghosh P. K.; Ghosh L. K.; ‘Development of a

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dosage form’; East. Pharm., 1999, 42(493), 131-134.

109. Trivedi P.; Jain D. K. and Bhatia N. M.; ‘Simultaneous analysis of salbutamol and

Bromohexine HCl from solid dosage form using multi wavelength UV- spectrophotometer’;

Indian Drugs, 1998, 35(9), 566-569.

110. Garg R. and Sharma A. K.; ‘Simultaneous determination of salbutamol and etofyllin by

third derivative UV-spectrophotometery’; Indian J. Pharm. Sci., 1997, 59(6), 295-298.

111. Sighvi I. and Chaturvedi S.C.; ‘Three spectrophotometric method for simultaneous

estimation of salbutamol and thiophyline from tablet’; Indian Drugs, 1998, 35(7), 421-428.

112. Patel K. G. and Rajput S. J.; ‘Estimation of secnidazole and lansoprozole in pharmaceutical

dosage formulation using differential spectrophotometry’; East. Pharm., 1998, 41(487), 115-

117.

113. Manawalan R. and Raghur Pratap D.; ‘A methemetical model for the determination of

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1999, 36(10), 648-650.

114. Trivedi P. and Gangwal S.; ‘Comparative evaluation of two different spectrophotometric

method for simultaneous estimation of spiranolatone and frusemide from combined dosage


115. Bharathi A.; Parimoo P. and Padama K.; ‘Determination of spironalactne with

hydrochlorthaizide and spironalactne with frusemide in combination formulation by UV-

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116. Liu, Tian-hu; Zhou, Mingdo; ‘Simultaneous sectrophotometric determination of two

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117. Berzas; Nevodo, J. J.; Castaneda Penalvo G. and Guzman Bernardo F. J.; ‘Simultaneous

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118. Garg R.; Gupta A. and Sharma A. K.; ‘Simultaneous determination of terbutaline sulfate

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119. Trivedi P. and Gangwal S.; ‘Simultaneous determination of terbutaline sulfate,

bromohexine HCL and guaiphenesin in three component tablet formulation by UV-

spectrophotometer’; Indian J. Pharm. Sci., 1999, 61(2), 128-130.

120. Trivedi P.; Jain D. K. and Agrawal D.; ‘Simultaneous estimation of tinidazole and

clotrimazole in tablet formulation’; Indian Drugs, 1998, 35(8), 499-502.

121. Goba S.; Agrawal S.; Qmary A. and Razdan P. K.; ‘Colorimetric estimation of tinidazole and

norfloxacin in combined solid dosage form’; East. Pharm., 1998, 41(483), 115-118.

122. Gandhimathi M.; et al; ‘Three simple spectrophotometric method for simultaneous

estimation of tinidazole and ofloxacine form tablet dosage form’; East. Pharm., 2001, 44(517),

137-139.

123. Trivedi P. and Sachan A.; ‘Spectrophotometric estimation of multi component formulation

containing tinidazole, doloxanide furoate and furazolidone’; Indian J. Pharm. Sci., 1999, 61(5),

301-303.

124. Prasad C. V. N.; Sripriya V.; Saha R. N. and Pramioo P.; ‘Simultaneous determination of

tinidazole, furazolidine and diloxamide furate in combined tablet preparation by second

derivative spectrophotometry ’; J. Pharm. Biomed. Anal., 1999,21 (5), 961-968.

125. Kargejha K. and Sarafi A. H. M.; ‘Spectrophotometric simultaneous determination of

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126. Suresh B.; Meyyanathan S. N.; Perumal G. N.; Syad A. and Lingeshwara P.; ‘Simultaneous

spectrophotometeric estimation of trianidine and ibuprofen in their dosage form’; Through 55th

Indian Pharmaceutical Congress Scientific Abstract, 2003/ GP-14.

127. Gao Jian-hua; Lin Peng and Chen Bin; ‘Simultaneous determination of trimethoprim and

norfloxacin in compound norfloxacin tablet by fluorescence spectrophotometry with out

separation’; Through Chemical Abstract, 2000,132/ 98249c.

128. Moharana R.; Tawathekar N. and Chaturvedi S.C.; ‘Simultaneous sectrophotometric

estimation of tripolidine HCl and pseudoephedrine HCl in pharmaceutical dosage form’; Indian

J. Pharm. Sci., 1996, 58(3), 93-95.

129. Trivedi P. and Sachan A.; ‘Simultaneous spectrophotometric estimation of triprolidine HCl

and phenyl propalamine HCl ’; East. Pharm., 1999, 42(496), 107-112.

130. Moharna R.; Kawatheakar N. and Chaturvedi S.C.; ‘Simultaneous Spectrophotometric

estimation of triprolidine HCl and Pseudoephedrine HCl in pharmaceutical dosage form’; Indian

J. Pharm. Sci., 1996, 58(3), 93-95.

131. ‘Simultaneous determination of pseudo ephedrine HCl and cetrizine HCl by derivative

spectroscopy ’; Indian Drugs, 2003, 40(11), 658-660.

132. Ashok Kumar; Anroop B. and Vijay K. S.; ‘Spectrophotometric method for simultaneous

estimation of nimusilide and paracetamol in tablet dosage form’; Indian Drugs, 2003, 40(12),

727-730.

133. Simultaneous determination of pseudo ephedrine HCl and cetrizine HCl by derivative

spectroscopy ’; Indian Drugs, 2003, 40(11), 658-660.

134. Chaple D. R.; Deshpande S. S. and Dombe M. S.; ‘ Simultaneous spectroscopic estimation

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135. Gaytri S.S.; Santha A.; Vaidyalingam V.; Ajithadas A. and Niraimathi V.; ‘Simultaneous

spectroscopic estimation of gliclazide and rasiglitazone from its pharmaceutical dosage form’;

Indian Drugs, 2003, 41(2), 112-113.

136. Kale U. N.; Nadu K. R. and Shingare M. S.; ‘Spectroscopic determination of ornidazole and

norfloxacine in tablet’; Indian J. Pharm. Sci., 2003, 65(4), 523-526.

137. Lad N. R.; Bhoir S. I.; Bhoir I. C. and Sundarsan M.; ‘ Concurrent assay of metformine and

glinepride in tablet using RP- HPLC with wavelength programming’; Indian J. Pharm. Sci., 2003,

65(6), 650-653.

138. .Rahman S.; Ahuja A.; Khar R. K. and Ali J.; ‘ Simultaneous spectrophotometric

determination of amoxycillin trihyderate and metrinidazole in dental films ’; Indian J. Pharm.

Sci., 2004, 66(1), 135-136.

139. Ravisankar S.; Vasudevan M.; Ravibabu J. and Nagarajan J. S. K.; ‘Estimation of

acetaminophen, dextrapropoxyphen and oxyphenbutaszone in from combined dosage form by

HPLC method’; Indian J. Pharm. Sci., 2000, 62(2), 122-125.

140. Argekar A. P. and Pawar S. G.; ‘Simultaneous determination of amilodipin and atenolol in

tablet by HPLC’; J. Pharm. Biomed. Anal., 2000,21 (6), 1132-1142.

141. Shinde V. M.; Desai B. S. and Tebdolkar N. M.; ‘Simultaneous determination of

amitriptyline HCl and chlordiozepoxide from tablet by HPLC’; Indian J. Pharm. Sci., 1995, 57(2),

66-67.

142. Rao J. R.; Kadam S. S. and Mahadik K. R.;‘HPLC determination of amlodipine and

benazepril HCl in tablet’; Indian Drugs, 2002, 39(7), 378-381.

143. Tsou T. L.; Wv J. R.; Young C. D. and Wang T. R.; ‘Simultaneous determination of

amoxycillin and clavulanic acid in pharmaceutical products by HPLC with B-cyclo dextrin

stationery phase’; J. Pharm. Biomed. Anal., 1997, 15(8), 1197-1205.

144. Suresh P. S.; Sivakuamr S. P. N.; Venketaraju D.; Trinanjan P.; Vasudavan M; and Nagarjan

J. S. K.; ‘Devlopment and validation of HPLC method for the simultaneous estimation of drugs

in selected anti-histaminic multi component dosage form’; Through 55th Indian Pharmaceutical


145. Xu X. and Stewart J. T.; ‘ HPLC method for aspirin-caffeine- butalbital and acetaminophen -

caffeine- butalbital mixture in tablet dosage forms using non-porous actadecyl siliane Colums’;

J. Liq. Chromatogr. Relat. Technol., 2000, 23(5), 769-779.

146. Trivedi P. and Sachan A.; ‘Simultaneous spectrophotometric analysis of liquid oral

formulation containing bromohexin HCl, diphenhydronon HCl and guaiphenesin’; Indian Drugs,

1999, 36(12), 735-738.

147. Kaskhedikar S. G. and Argal Ameeta,; ‘Simultaneous estimation of bromohexine HCl and

Cephalexine in capsule by HPLC’; Indian Drugs, 2001, 38(3), 137-139.

148. Badwe N.; Garg A.; Eapen D. and Seth P. D.; ‘‘Simultaneous estimation of bromohexine

HCl, phnyl praopalamine HCL and Chlorphenaramine meleate in combined liquid dosage form

by HPLC’; East. Pharm., 1995, 38(452), 179-180.

149. Dinc, F; ‘ A comparative study of the ratio spectra derivative spectrophotometry vierardt’s

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150. Tipre D. N. and Kasture A. V. ; ‘Simultaneous estimation of ceprofloxacin and tinidazole

in tablet dosage form using spectrophotometric and HPLC method ’; Indian Drugs, 2000, 37(3),

148-154.

151. Zarapkar S. S.; Rane A. V. and Rane S. H.; ‘HPLC determination of ciprofloxacin HCl and

tinadazole in pharmaceutical preparation ’; Indian Drugs, 1999, 36(5), 408-410.

152. Bhatia M. S.; Kaskhedikar S. G. and Chaturvedi S.C.; ‘HPLC estimation of ciprofloxacin HCl

and tinidazole from tablet’; Indian J. Pharm. Sci., 1999, 61(5), 311-312.

153. Nan Nan and Chen Hua; ‘HPLC determination of codeine phosphate, ephedrine HCl and

chlorphenaramine maleate in cocifedra-C syrup’; Through Chemical Abstract, 2000,132/

185522g.

154. Ji Yibing and Chen Yuyong; ‘Simultaneous determination of dextromethorphen and

pseudo ephedrine in compound tablet by HPLC’; Through Chemical Abstract, 2002,136/

43001v.

155. Shinde V. M.; Desai B. S. and Tebdolkar N. M.; ‘Simultaneous determination of diclofenic

sodium, paracetamol and chlormerzonone by HPLC from tablet’; Indian J. Pharm. Sci., 1995,

57(1), 35-37.

156. Argekar A. P. and Pawar S. G.; ‘Simultaneous determination of diloxanide furoate and

tinidazole in tablet by HPLC’; Through Chemical Abstract, 2000,132/ 171246h.

157. Balaprabhakar and Deshpande S.G.; ‘Simultaneous estimation ethniyl estradiol and

levonorgestral from transdermal patch by HPLC’; Indian J. Pharm. Sci., 1999, 61(1), 12-15.

158. Vidya V. V.; Khanolkar M. and Gadre J. N.; ‘Isocratic, simultaneous HPLC determination of

frusimide and spironolactone in pharmaceutical dosage form by ion- pair chromatography;

Indian Drugs, 2002, 39(7), 373-377.

159. Suzen Sinan and Akay Cemal; ‘Simultaneous determination of guaifenesin and codeine

phosphate in tablet by HPLC’; Through Chemical Abstract, 2000,132/ 40654s.

160. Li-Yongguig, Tian, Zixin, Zhao Wen; Zhu, Jihong; ‘ Determination of guaifenesine,

pseudoephedrine HCl and dextromethorphen hydrobromide in related oral solution by HPLC’;

Through Chemical Abstract, 2000,132/ 298926k.

161. Argekar A. P. and Sawant J. G.; ‘ A gradient reversed phase HPLC method for

simultaneous determination of hydrochlorthaizide and losartan potassium from tablet’; Anal.

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162. Jiang Zibin and Yuan Jimin; ‘Determination of ibuprofen and dextromethorphen HCl in

capsule by RP-HPLC’; Through Chemical Abstract, 2000,132/ 284360j.

163. Wagh P. J.; and Pai N.; Devlopment and validation of HPLC method for simultaneous

determination of lavnivudine and zidovudine from pharmaceutical preparation’; Indian Drugs,

2002, 39(12), 654-657.

164. Zhang Qing; ‘ HPLC determination of metranidazole, clotimazole and chlorhexidne acetate

in their compound effervescent tablet’; Through Chemical Abstract, 2002,136/ 58936c.

165. Vidya V. V.; Khanolkar M. and Gadre J. N.; ‘Simultaneous assay of nimuselide and

camplofine in pharmaceutical preparation using HPLC’; Indian Drugs, 2001, 38(4), 170-173.

166. Zarapkar S. S. and Kanyawar N. S.; ‘Simultaneous determination of norfloxacin and

metranidazole in tablet by HPLC’; Indian Drugs, 1999, 36(5), 293-295.

167. Halkar U. P.; Ankalkope P. B. and Rane S. H ‘HPLC determination of paracetamol, caffeine

and prophyphenazone in tablet’; Indian Drugs, 2002, 39(5), 293-296.

168. Suresh B.; Senthilkumar M; Jayaseelan S.; Gopinanth R.; Vasudavan M; and Nagarjan J. S.

K.; ‘A HPLC method for the simultaneous estimation of paracetamol, chlorphenaramine

maleate, phenylepherine and caffeine in formulation’; Through 55th Indian Pharmaceutical


169. Bharathi A.; Parimoo P. and Atul B. V.; ‘Determination of propylphenazone and

ketoprophen in drug formulation by HPLC’; Indian J. Pharm. Sci., 1996, 58(5), 205-206.

170. ‘Determination of pyridoxine HCl, nephazoline nitrate, chlorpheniramine meleate and

panthenol in some collyria by HPLC’; Through Chemical Abstract, 2000,132/ 171211t.

171. Wang, Junqiu; Yu, Li and Dai, Hog; ‘HPLC determination of sodium cromoglycate and

salbutamol sulfate in aerosol’; Through Chemical Abstract, 2000,132/ 171237f.

172. Suresh B.; Rajesh R.; Gopinanth R.; Vasudavan M; and Nagarjan J. S. K.; ‘A HPLC method

for the simultaneous estimation of terbutaline sulfate and guaiphenesin’; Through 55th Indian

Pharmaceutical Congress Scientific Abstract, 2003/ GP-48.

173. Vasudevan M.; Ravishankar S.; George M. and Ravi J. ; ‘Simultaneous estimation of

terbutaline, bromohexine and guaiphenesine in soft geletine capsule by HPLC method’; Indian

Drugs, 2000, 37(10), 497-498.

174. Shenoy K. P. R.; Krishnamurthy K. S. and Iyengar V. ; ‘HPLC method for simultaneous

determination of terbutaline, guaiphenesin and ambroxol in formulations’; Indian Drugs, 2001,

38(8), 428-432.

175. Zhang Y.; ‘ Determination of theophylline and Phenobarbital in long-acting aminophylline

tablet by HPLC’; Through Chemical Abstract, 2000,132/ 298930g.

176. Chen Ye; Zheng;and Jiayeng; ‘Simultaneous determination of content of thiophylline and

guaifenesin by HPLC’; Through Chemical Abstract, 2000,132/ 40615e.

177. Mahadik K. R.; Aggrawal H. and Kaul N.; ‘ Devlopment and velidation of HPLC method for

simultaneous estimation of trihexyphenidyl HCl and chlorpromazine HCl for tablet dosage


178. El-Bayomi and Abd El-Aziz; ‘ HPLC using diode array determination spectrodesiometric

method for the simultaneous determination of vitamin A, E, and D3 in multivitamin

preparation’; Through Chemical Abstract, 2000,132/ 242013t.

179. Gowri N.; Vidhyalingam V. and Santha A.; ‘Simultaneous estimation of amlodipine and

benazepril from tablet by RP- HPLC; Indian Drugs, 2001, 38(10), 332-335.

180. Zarapkar S. S. and Kanyawar N. S.; ‘Simultaneous estimation of amlodipine and losarton

potassium in pharmaceutical dosage form by RP- HPLC; Indian Drugs, 2002, 39(6), 341-343.

181. Yang Zemini and Chen Ji-heng;‘ Simultaneous determination of amoxicillin and

clavulanate by RP-HPLC’; Through Chemical Abstract, 2000,132/ 40638q.

182. Du Z.; Chen J. J. and Young Z. M.; ‘Simultaneous RP-HPLC determination of two component

in amoxycillin and clavulanate potessium’ Through Int. Pharm. Abstract, 2000, 37(16),

3709471.

183. Zarapkar S. S.; Halkar U. P. and Rane S. H. ; ‘RP- HPLC determination of amoxycillin,

probencid and tinidazole in tablet’; Indian Drugs, 1999, 36(3), 181-184.

184. Zarapkar S. S.; Halkar U. P. and Rane S. H.; ‘RP- HPLC determination of ampicilline and

probencid in capsule’; Indian Drugs, 2000, 37(4), 200-203.

185. Shinde V. M. and Shabadi C. V.; ‘Simultaneous determination of cefazoline and cefotoxime

from injection by RP-HPLC’; Indian J. Pharm. Sci., 1998, 60(5), 313-314.

186. Pi, Li; ‘ Determination of cefelexine and trimethoprim in compound cefelexine capsule by

RP-HPLC’; Through Chemical Abstract, 2000,132/ 284319c.

187. Nalini C. N.; Kavitha K. and Kumaravel S.;‘Simultaneous determination of ceprofloxacine

and arnidazole by RP-HPLC’; Through 55th Indian Pharmaceutical Congress Scientific Abstract,

2003/ GP-45.

188. Zarapkar S. S.; Halkar U. P. and Rane S. H.; ‘RP-HPLC determination of cetrizine and

pseudo ephedrine HCl in tablet ’; Indian Drugs, 1998, 35(10), 658-661.

189. Raman B. Kanumular G. V. and Bhoir I. C.; ‘Concurrent analysis of multi- component

dosage formulation containing chlophenaramine meleate, phenylepherine HCl and caffeine and

acetaminophen by RP-HPLC with wavelength programming ’; Indian Drugs, 2001, 38(4), 203-

207.

190. Zarapkar S. S.; Halkar U. P. and Bhandari N. P.; ‘Simultaneous estimation of cinnarizine

and domperidone in tablet by RP- HPLC’; Indian Drugs, 2000, 37(6), 295-298.

191. Argerkar A.P. and Pawar S. G.; ‘Simultaneous determination of ciprofloxacin and

tinadazole in pharmaceutical preparation by RP-HPLC’; Indian Drugs, 1999, 36(5), 399-402.

192. Zarapkar S. S.; Rane A. V. and Rane S. H.; ‘HPLC determination of ciprofloxacin HCl and

tinadazole in pharmaceutical preparation ’; Indian Drugs, 1999, 36(5), 408-410.

193. Shenoy K. P. R.; Krishnamurthy and Vinod M. V.; ‘Simultaneous determination of codine

phosphate and chlorphenaramine maleate in formulation by RP- HPLC; Indian Drugs, 1999,

36(8), 513-516.

194. Shenoy K. P. R. and Krishnamurthy K. S.; ‘Determination of codine phosphate, doxylamine

succinate, paracetamol and caffeine in combined dosage formulation by RP- HPLC’; Indian

Drugs, 2000, 37(10), 486-488.

195. Raman B. and Patil D.; ‘Simultaneous estimation of dextropropoxyphen HCl, diclofenic

sodium and paracetamol in capsule by RP-HPLC’; Indian Drugs, 2001, 38(1), 36-39.

196. Raman B. and Patil D.; ‘RP- HPLC for Simultaneous estimation of domamethasone, p-

chlrophenol and thymol in dental solution’; Indian Drugs, 2002, 39(9), 487-490.

197. Zarapkar S. S.and Kanyawar N. S.; ‘Simultaneous estimation of domperidon and

omeprazole in pharmaceutical dosage form by RP- HPLC; Indian Drugs, 2002, 39(4) 217-221.

198. Zarapkar S. S.; Halkar U. P. and Rane S. H. ‘RP- HPLC determination of Doxylamine

succinate and pyridoxine HCl in tablet’; Indian Drugs, 1999, 36(7), 449-452.

199. Zarapkar S. S.; Halkar U. P. and Bhandari N. P.; ‘Simultaneous determination of

fexofenadine HCl and pseudoephedrine sulphate in pharmaceutical dosage form by RP- HPLC’;

Indian Drugs, 2000, 37(9), 421-425.

200. Xia, Xiaoping and Zhou, Yuehang; ‘ Determination of flucanozole, metranidazole and

choramphinicol in compound flucanazole cream by RP-HPLC’; Chemical Abstract, 2000,132/

185523h.

201. Shinde V. M and Khanolkar D. H.; ‘RP- HPLC method for estimation of gilendsmine and

metformineHCl from combined dosage form’; Indian Drugs, 1999, 36(12), 739-742.

202. Gandhimathi M.; Anandkumar K.; Cheriyan A. and Rai T. K.; ‘Simultaneous estimation of

gliclazide and metformine HCl in tablet using RP-HPLC’; Indian J. Pharm. Sci., 2003, 65(4), 530-

531.

203. Duby A. and Shukla I. C.; ‘ Microgram determination of glipiozide and metformine HCl in

pharmceutical preparation by HPLC method’; Indian Drugs, 2002, 39(8), 446-449.

204. Zarapkar S. S. Kulkarni S. K and Kanyawar N. S.; ‘Simultaneous estimation of glipizide and

metformine in pharmaceutical dosage form by RP- HPLC; Indian Drugs, 2001, 38(10), 535-538.

205. Shah R. and Sahajia B. N.; ‘Simultaneous estimation of lasartan potassium and

hydrochlothiazide in pharmaceutical dosage form by RP-HPLC’; Through 55th Indian

Pharmaceutical Congress Scientific Abstract, 2003/ G-5.

206. ‘Simultaneous estimation of lomefloxacine HCl, prothionamide and pyrizinamide in

pharmaceutical dosage form by RP-HPLC’; The Pharma Review, 2003, 1(3), 87-89.

207. Gaikwad N. J. and Wanjari D. B.; ‘Simultaneous estimation of metformine HCl and

pigglitazone in combined dosage form by RP-HPLC’; Through 55th Indian Pharmaceutical


208. Raman B.; Kulkarni S. K. and Kayawar N. S.; ‘Simultaneous estimation of methocarbamol

and nimuselide in pharmaceutical dosage forms form by RP- HPLC’; Indian Drugs, 2002,

39(10), 536-540.

209. Vasudevan M.; Ravishankar S.; Ravibabu T. and Nanjan M.J.; ‘Simultaneous estimation of

methocarbamol, ibuprofen and paracetamol by RP-HPLC’; Indian Drugs, 2000, 37(8), 386-389.

210. Shinde V. M and Raman B.; ‘Simultaneous determination of nicotinic acid and meclozine

HCl in tablet by RP- HPLC’; Indian Drugs, 1998, 35(12), 748-753.

211. Nagoji K. E. V.; Kirankumar M.; Vijayasrinivas S.; Satishkumar M. and Rao M.E. B.;

‘Simultaneous RP-HPLC estimation of nimesulide and diclofenic sodium’; Indian J. Pharm. Sci.,

2003, 65(4), 407-409.

212. Kale U. N.; Naidu K. R. and Shingare M. S.; ‘RP-HPLC method for simultaneous estimation

of nimesulide and Tizanidine HCl in tablet’; Indian J. Pharm. Sci., 2003, 65(3), 315-318.

213. Zarapkar S. S.; Halkar U. P. and Bhandari N. P.; ‘Simultaneous determination of

nimuselide and chlorzoxazone in pharmaceutical dosage form by RP- HPLC’; Indian Drugs,

2000, 37(10), 469-473.

214. Kale U. N.; Naidu K. R. and Shingare M. S.; ‘Simultaneous determination of norfloxacin and

ornidazole in pharmaceutical dosage form by RP-HPLC’; Indian Drugs, 2003, 40(7), 397-400.

215. Halkar U. P. and Ankalkope P. B. ; ‘RP- HPLC determination of ofloxacin and tinidazole in

tablet’; Indian Drugs, 2000, 37(12), 585-588.

216. Singh R. A.; Kumar D.; Kumar R. and Sourabh A.; ‘Simultaneous estimation of ornidaole

and ofloxacine in pharmaceutical dosage form by RP-HPLC’; Through 55th Indian


217. Nagoji E. V. and Srinivas S. V.; ‘Simultaneous estimation of paracetamol and nimesulide in

tablet by RP- HPLC’; Asian J. of Chemistry, 2002, 14(2), 1004-1008.

218. Zarapkar S. S.; Halkar U. P. and Bhandari N. P.; ‘RP- HPLC determination of paracetamol,

ibuprophen and methocarbamol in tablet’; Indian Drugs, 1999, 36(11), 710-713.

219. Raman B. and Patil D.; ‘Simultaneous estimation of paracetomol and nemuselide in tablet

by RP- HPLC’; Indian Drugs, 2000, 37(10), 437-440.

220. Raman B. Kanumular G. V. and Bhoir I. C.; ‘Concurrent analysis of multi- component

dosage formulation containing phenylpropanolamine HCl, cetrizine diHCl and acetaminophen

by RP-HPLC with wavelength programming ’; Indian Drugs, 2001, 38(6), 294-298.

221. Shah D. A.; Shenkar M. B.; Modi V. D.; Patel B. J. and Geetha M.; ‘Estimation of

Picglitazone and metformine by derivative spectrophotometery and RP-HPLC in tablet’;

Through 55th Indian Pharmaceutical Congress Scientific Abstract, 2003/ G-17.

222. Raman B. and Kanumula G. V.; ‘Simultaneous determination of pseudoephedrine HCl and

loratidine HCl in pharmaceutical dosage form by RP- HPLC’; Indian Drugs, 2000, 37(12), 574-

576.

223. Bhatia M. S.; Kaskhedikar S. G. and Chaturvedi S.C.; ‘ Chromatographic estimation of

pseudoephedrine HCl, dextromethorphen hydrobromide and triprolidone HCl from multi

component tablet’; Indian J. Pharm. Sci., 2000, 62(2), 61-62.

224. Raman B. and Shinde V. M.; ‘Simultaneous determination of pyrantel pomoate and

mebendazole in tablet by RP- HPLC’; Indian Drugs, 1999, 36(3), 167-172.

225. Dhora U. J. and Shetkar N. B.; ‘RP- HPLC determination of ramipril and amlodipine in

tablet’; Indian Drugs, 1999, 36(10), 638-641.

226. Zarapkar S. S. and Rane S. H.; ‘RP- HPLC determination of ramipril and

hydrochlorothiazide in tablet’; Indian Drugs, 2000, 37(12), 589-593.

227. Raman B. and Kanumular G. V.; ‘Simultaneous determination of ranitidine HCl and

domperidom in pharmaceutical dosage form by RP-HPLC’; Indian Drugs, 2000, 37(8), 375-378.

228. Raman B. and Patil D.; ‘Simultaneous estimation of sertraline and alprozalam in capsule

by RP-HPLC’; Indian Drugs, 2001, 38(12), 638-641.

229. Suresh B.; Ravisankar S.; Vasudevan M.; Nanjan M. J. and Nooruddeen N.; ‘RP-HPLC

method for the estimation of tinidazole and furozolidine in formulation’; Indian Drugs, 1998,

35(10), 667-668.

230. Raman B. and Patil D.; ‘RP- HPLC for Simultaneous estimation of tizanidine and nimesulide

in tablet’; Indian Drugs, 2002, 39(7), 392-394.

231. Hassib S. T.; El-Bagary and Ramzia I.; ‘Simultaneous determination of triamterene and

xipamide in pharmaceutical dosage form by RP-HPLC and densitometric method’; Through

Chemical Abstract, 2002,136/ 13993f.

232.Prashant M. and Subramenion G.; ‘Estimation of trianidine, diclofenic and paracetamol in

multi component dosage form by RP-HPLC method’; Through 55th Indian Pharmaceutical


233. Gandhimathi M.; Ravi t. k.; Varghese A. and Ninan A.; ‘RP-HPLC determination of

simvastatin and Nicotinic acid in tablets ’; Indian Drugs, Indian Drugs, 2003, 40(12), 707-711.

234. Shabadi C. V.; Shelar B. A. and Shelar A. R.; ‘Simultaneous determination of cephalexin

acid cefadoxil in pharmaceutical preparation by quantitative thin layer chromatography’;

Indian Drugs, 1998, 35(12), 766-770.

235. Argekar A. P. and Pawar S. G.; ‘Simultaneous HPTLC determination of cinnarzine and

domperidon maleate in formulation’; Through Chemical Abstract, 2000,132/ 40649u.

236. Kadam S. S.; Zahid Zaheer; Mhaske D.; Bairial J. and Daneshwar S. R.; ‘Method

development and validation of gliclazide and metformine HCl from tablet using HPTLC’;

Through 55th Indian Pharmaceutical Congress Scientific Abstract, 2003/ G-28.

237. Gayatri S.; Vidhyalingam V. and Santha A.; ‘Simultaneous HPTLC determination of

glidazide and rosiglitazone in tablet’; Indian J. Pharm. Sci., 2003, 65(6), 663-665.

238. Devarajan P. V.; Adani M. H. and Gandhi A. S.; ‘Simultaneous determination of lignocaine

and phenylephrine HCl by HPTLC’; J. Pharm. Biomed. Anal., 2000,22 (4), 685-690.

239. Singh R. A.; Singh A.; Kumar R. and Sourabh A.; ‘Simultaneous estimation of L-lysine HCl

and DL- methionone in multi vitamin oral dosage form by HPTLC’; Through 55th Indian


240. Chatki P.K.; Manwar J. V. and Tajne M. R.;‘Simultaneous estimation of methocarbamol and

nimesulide in tablet by HPTLC’; Through 55th Indian Pharmaceutical Congress Scientific

Abstract, 2003/ GP-39.

241. Argekar A. P. and Sawant J. G.; ‘Simultaneous determination of paracetamol and

mefanamic acid in tablet by HPTLC’; Through Chemical Abstract, 2000,132/ 27836b.

242. Sane R. T.; Fransis May; Khedkar S.; Pawar S. and Moghe A.; ‘Simultaneous HPTLC

determination of pseudoephedrine sulphate and laratadine from combined dosage form’;

Indian Drugs, 2001, 38(8), 436-438.

243. Mahadik K. R.; Aggarwal H. and Kaul N.; ‘Simultaneous HPTLC estimation of

trifluoperazine HCl, trihexylphenidyl HCl and chlorpromazine HCl in tablet dosage form’; Indian

Drugs, 2003, 40(6), 340-344.

244. Gawri N.; Vaidhyalingam V. and Santha A.; ‘HPTLC method for the simultaneous

estimation of amlodipine besylate and benazepril HCl tablets’; Indian Drugs, 2003, 40(11),

645-648.

245. Aukunuru J. V.; Kampella U. B.; Betagri G. V.; ‘Simultaneous HPLC analysis of

acetaminophen, salicylamide, phenyltoloxamine and related products’; J. Liq. Chromatogr.

Relat. Technol., 2000, 23(4), 565-578.

246. Panderi I. E.; Parissi and Poulou M.; ‘Simultaneous determination of benazepril HCl and

hydrochlorthaizide by micro- based liquid chromatography ’; J. Pharm. Biomed. Anal., 1999,21

(5), 1017-1024.

247. Degin T.; Akay C. and Burykafsar K.; ‘Simultaneous determination of codeine and ethyl

morphine HCl in tablet formulation using liquid chromatography’; J. Pharm. Biomed. Anal.,

2001,26 (1), 15-21.

248. Trivedi P. and Gangwal S.; ‘Liquied chromatographic estimation of diclofenic sodium and

chlorzoxazone from tablet’; East. Pharm., 2000, 43(505), 139-140.

249. Berzas; Nevodo, J. J.; and Llerena M. J.; ‘Determination of fluoxetine, fluvoxamine and

clomipramine in pharmaceutical formulation by capillary gas chromatography ’; J. Chrmatogrp.

Sci., 2000,38(5), 200-206.

250. Xu X.; Xiao-Lui and Stewart J. T.; ‘MEKC determination of guaifenesin , pseudoephedrine

and dextromethorphan in capsule dosage forms’; J. Liq. Chromatogr. Relat. Technol., 2000,

23(1), 1-13.

251. Singh R. A.; Singh D. K. and Anna A.; ‘Simultaneous estimation of oxybenzone and

octylmethoxy cinnamate by GLC’; East. Pharm., 1999, 42(493), 121-124.

Table 1: Combination formulations used for therapies

S. No. Combinations Use

1 Ciprofloxacin and phenyl ephedrine HCl Eye

2 Atropine and chloremphenicol Eye

3 Diclofenac and gentamycin Eye

4 Tropicamide and phenylephine HCl Eye

5 Phenylephine HCl, Naphazoline HCl, Menthol and Camphor Eye

6 Chloramphinicol, clotrimazole, beclamethasone and lignocain Eye

7 Gentamycin, clotrimazole, beclamethasone and lignocain Eye

8 Phenylephrine HCl and Naphazoline HCl and Menthol and Chlorbutol Nasal Prep.

9 Clonidine and Hydrochlorthaizide CVS

10 Clonidine and Chlorthalidone CVS

11 Reserpine and Dihyrallzine CVS

12 Reserpine and Dihyrallzineand Hydrochlorthaizide CVS

13 Atenolol and Chlorthalidone CVS

14 Atenolol and Alprazolam CVS

16 Isosorbide mononitrate and Aspirin CVS

17 Tranexamic acid and mefenamic acid Coagulant

18 Ticlopidine HCl and Aspirin Anticoagulant

19 Clopidogrel and Aspirin Anticoagulant

20 Triprolidine HCl, Psudeoephedrine HCl andDextromethorphenRespiratory System

21 Terfinidine andDextromethorphenRespiratory System

22 Bromohexine HCl and guaiphenesin and Salbutamol and MentholRespiratory System

23 Ambroxol and guaiphenesin and Salbutamol and MentholRespiratory System

24 Lorotadine and Psudeoephdrine HClRespiratory System

25 Ambroxol and Psudeoephdrine HClRespiratory System

26 Terfinidine, Psudeoephdrine HClRespiratory System

28 Neomycin, Bacitracin and SufacetamideTopical intiinfective

29 Tolnaftate, Chlorhexidine and Salicylic acidTopical Antifungal

30 Quiniodochlor and HydrocortisonTopical Antifungal

31 Beclomethasone, Neomycine and ClotrimazoleTopical Antifungal

32 Beclomethasone, gentamycine and ClotrimazoleTopical Antifungal

33 Beclomethasone, Neomycine and EconozoleTopical Antifungal

34 Phenylbutazone, Propylphenazone and Paracetamol NSAID

35 Indomethacin and Paracetamol NSAID

36 Diclofenic sodium, Serratiopeptidase and Paracetamol NSAID

37 Diclofenic sodium, Dextropropoxyphen HCl and Paracetamol NSAID

38 Diclofenic sodium, Megnesium trisilicate and Paracetamol NSAID

39 Meloxicam and Paracetamol NSAID

40 Nimusilide and Serratiopeptidase NSAID

41 Nimusilide, Dextropropoxyphen HCl and Paracetamol NSAID

42 Ibuprofen and Dextropropoxyphen HCl NSAID

43 Propyphenazone, Paracetamol and Caffine NSAID

44 Glucosamine and Methylsulfonylmethane NSAID

45 Glucosamine and Vit. C NSAID

46 Glucosamine, Vit. C and calcium carbonate NSAID

47 Glucosamine and Chondroitin NSAID

48 IbuprofenandMephenesin, Methyl salicylate and Methnol NSAID

49 Diclofenic sodium, Methocarbamol and Paracetamol NSAID

50 Methocarbamol and Ibuprofen NSAID

52 Carisoprodol, Paracetamol and Caffeine NSAID

53 Carisoprodol and Ibuprofen NSAID

55 Ibuprofen, Chloroxazone and Paracetamol NSAID

56 Tizanidine and Nimusilide NSAID

57 Tizanidine and Diclofenic sodium NSAID

58 Tizanidine, Diclofenic sodium and Paracetamol NSAID

59 Tizanidine, Nimusilide and Paracetamol NSAID

60 Tizanidine and Mefanamic acid NSAID

61 Tizanidine and Refecoxib NSAID

62 Ampicillin and Sulbactum Antiinfective

64 Amoxycillin and Bromhexine / Ambroxal Antiinfective

68 Cephalexin and Bromhexine / Ambroxal Antiinfective

69 Cephalexin and Carbocisteine Antiinfective

71 Cephadroxil and Probencid Antiinfective

74 Cephuroxime and Serratiopeptidase Antiinfective

75 Cefixime trihydrate and Lactic acid bacillus Antiinfective

76 Cefoperazone sodium and Sulbactum sodium Antiinfective

77 Erythromycine and Bromohexine Antiinfective

78 Roxithromycine and Bromohexine/ Ambroxol Antiinfective

79 Roxithromycine and Serratiopeptidase Antiinfective

80 Oxytetracycline and Lidocain Antiinfective

81 INH and Vit B6 Anti T B

82 INH and Thaiacetazone Anti T B

83 INH and Rifampicin Anti T B

84 INH, Rifampicin and Vit B6 Anti T B

85 INH , Rifampicin and Pyridoxine Anti T B

86 INH and Ethembutol Anti T B

87 INHandEthembutol and Rifampicin Anti T B

88 INHandRifampicin and Vit B6and Pyrazinamide Anti T B

89 Tinidazole and doxicycline Antiprotozoal

90 Metrinidazole and Diloxamide Antiprotozoal

91 Tinidazole and doxicyclineand Tetracycline Antiprotozoal

92 Ornidazole and Ciprofloxacin Antiprotozoal

93 Diethylcarbamazine and Chlorphenaramine maleate Antiprotozoal

94 Sulphamethzole and Pyrimethamine Antimalarial

95 Chloroquine and Primaquine Antimalarial

96 Stavudine and Lamivudine Antimalarial

97 Zidovudine and Lamivudine Antimalarial

98 Zidovudine and Lamivudineand Navirpine Antimalarial

99 Stavadine and Lamivudineand Navirpine Antimalarial

100 Ethinyloestradiol and MethyltestosteroneEndocrine System

101 Ethinyloestradiol and DesogestrolEndocrine System

102 Gliclazide and Chromium Antidibetics

103 Chlorpropamide and Phenformine Antidibetics

104 Metformineand Glibenclamide Antidibetics

105 MetformineandGlipizideand Polynicotinate Antidibetics

106 MetformineandGlimepride Antidibetics

107 MetformineandRosiglitozone Antidibetics

108 MetformineandPioglitozone Antidibetics

109 Glimepride and Rosiglitazone Antidibetics

110 GlimeprideandPioglitozone Antidibetics

111 Simvastin and Nicotinic acid Hypolipid

112 Atrovastine and Aspirin Hypolipid

113 Eicosapentacnoic acid and Decosahexaenoic acid Hypolipid

114Eicosapentacnoic acid and Decosahexaenoic acidand A-tocopreryl acetated Hypolipid

115 Ibuprofen and colchicineDrugs used in gout

116 Chlorphenaramine maleateand Trithioparamethoxy phenyl propeneAllergy & Immunology

117 Lidocain and Prilocain Anaesthetics

Table- 2

List of multi-component formulation estimated by UV-visible spectrophotometer

with respective reported references.

Sr. NO. Combination of drugs Therapeutic Use Ref. No.

1 Acetyl salicylic acid, caffeine and codeine phosphate NSAID 7

2 Acrivastine and pseudo ephedrine HCl Respiratory System 8

3 Ambroxol HCl and cetrizine Respiratory System 9

4 Amiloride, hydrochlorothiazide and atenolol CVS 10

5 Amlodipine besylate and enalapril maleate CVS 11

6 Amlodipine besylate and lisinopril CVS 12

7 Amlodipine besytale and lisinopril CVS 13

8 Amoxycillin and probencid Antiinfective 14

9 Amoxycillin, ampicillin and cloxacillin Antiinfective 15

10 Ampicillin and cloxacillin Antiinfective 16

11 Aspirin compound tablet NSAID 17

12 Aspirin, acetaminophen and ascorbic acid NSAID 18

13 Atenolol and nefedipine CVS 19

14 Benazepril and amlodipine besylate CVS 20

15 Benazepril and hydrochlorthiazide CVS 21

16 Benhexol HCl and trifluperazine HCl Respiratory System 22

17 Bromohexine HCl and pseudo ephedrine HCl Respiratory System 23

18Bromohexin HCl, diphenhydronon HCl and guaiphenesin

Respiratory System 24

19 Bromohexine HCl and pseudo ephedrine HCl Respiratory System 25

20 Bromohexine HCl, dextromethorphen hydrobromide Respiratory 26

and chlorphenaramine malate System

21 Captopril and hydrochlorthiazid CVS 27

22 Captopril and hydrochlorthiazide CVS 28

23 Cefadoxil and ambroxal Antiinfective 29

24 Cefelexin and probencid Antiinfective 30

25 Cefuroxime axetil and probencid Antiinfective 31

26 Cehpalexine and probencid Antiinfective 32

27 Cetrizine and pseudoephedrine HCl Respiratory System 33

28Chloramphinicol and dexamethasone sodium phosphate Antiinfective 34

29 Chloraxazone and paracetamol NSAID 35

30 Cloraxazone, diclofenic sodium and paracetamol NSAID 36

31 Chlordiazepoxide and clindinium bromide Antipsycotic 37

32 Chloroxazone and paracetamol NSAID 38

33 Chlorthalidone and spironolactone CVS 39

34 Chlorzoxasone and nimesulide NSAID 40

35 Chlorzoxazone and nimusalide NSAID 41

36 Chlorzoxazone and nimuselide NSAID 42

37 Cinnarizine and domperidone GIT 43

38Dextromethorphen hydrobromide and Bromohexine HCl


39 Diazepam and pyridoxine Antipsycotic 45

40 Diclofenic sodium, paracetamol and chlormerzonone NSAID 46

41 Diloxamide furoate and tinidazole Antiinfective 47

42 Dilxamide furoate and tinidazole Antiinfective 48

43 Dipyryone and caffeine 49

44 Doclofenic sodium and paracetamol NSAID 50

45 Domperidon and omeprazole GIT 51

46 Dopamine and ephedrine Antipsycotic 52

47 Ethniyl estradiol and levonorgestral Endocrine System 53

48 Folic acid, thiamine, riboflavin and pyridoxal Multivitamine 54

49 Gliclazide and metformin HCl Antidibetics 55

50 Glipizide and metformine Antidibetics 56

51 Hydrochlorothiazide and lasarton potassium CVS 57

52 Hydrochlorothiazide and metoprolol CVS 58

53Hydrochlorthiazide and amiloride HCl or with spironolactone CVS 59

54 Ibuprofen and chlorzoxane NSAID 60

55 Ibuprofen and methocarbamol NSAID 61

56 Imipramine HCl and Diazepam Antidepressant 62

57 Letofylline and theophylline Respiratory System 63

58 Lisinopril and hydrochlorothiazide CVS 64

59 Losarton potassium and amlodipine CVS 65

60 Losarton potassium and hydrochlorthiazide CVS 66

61 Mebendazole and pyrantel pomate Antiinfective 67

62 Meclozine HCl and nicotinic acid Antidebetics 68

63 Medazepam and hyoscine butylbromide 69

64 Mefenamic acid and paracetamol NSAID 70

65 Melatonin-pyridoxine Endocrine System 71

66 Metoprolol and hydrothiazide Antidibetics 72

67 Metranidazole and nalidix acid Antiinfective 73

68 Metronidazole and norfloxacin Antiinfective 74

69 Nalidixic acid and metronidazole Antiinfective 75

70 Nalidixic acid and metronidazole Antiinfective 76

71 Nimesulide and chlorzaxasone NSAID 77

72 Nimesulide and chlorzaxasone NSAID 78

73 Nimesulide and diclofenic sodium NSAID 79

74 Nimesulide and tizanidine HCl NSAID 80

75 Norfloxacin and tinidazole Antiinfective 81



78 Noscopine, chlorphenaramine maleate and ephedrine Respiratory 84

HCl System

79 Oflaxacine and tinidazole Antiinfective 85

80 Pantoprozole and domperidone GIT 86

81 Paracetamol and chlorzaxasone NSAID 87

82 Paracetamol and mefenamic acid NSAID 88

83 Paracetamol and nemuselide NSAID 89

84 Pefloxacine and metrinidazole Antiinfective 90

85Phynyl propanalamine, chlorphenaramine and Bromohexine HCl


86Phynyl propanalamine, chlorphenaramine malate and dextromethorphen hydrobromide


87 Propranolol HCl and hydrochlorthiazide CVS 93

88 Propranolol HCl-diazepam CVS 94

89 Pseudo ephedrine HCl and ibuprofen NSAID 95

90Pseudo ephedrine HCl, and dextromethorphen hydrobromide


91Pseudo ephedrine HCl, dextromethorphen hydrobromide and chlorphenaramine malate


92Pseudo ephedrine sulphate, dexbrompheniramine melete and loratadine


93 Pseudo mefanamic acid and paracetamol NSAID 99

94 Pyridoxal , pyridoxamine and pyridoxic acid Multivitamine 100

95 Pyridoxine HCl and metformin HCl Antidebetics 101

96 Rifampicin, pyrizinamide and isoniazide Antiinfective 102



99 Rifampicin and isoniazide Antiinfective 105




103 Salbutamol and Bromohexine HCl Respiratory System 109

104 Salbutamol and etofyllinRespiratory System 110

105 Salbutamol and thiophyline Respiratory System 111

106 Secnidazole and lansoprozole Antiinfective 112

107 Secobarbital sodium and amobarbital sodium Antipsycotic 113

108 Spiranolatone and frusemide Diuretics 114

109Spironalactne with hydrochlorthaizide and spironalactne with frusemide Diuretics 115

110 Sulfamethoxazole Antiinfective 116

111 Sulfaquinozaline, sulfamethzine and pyrimethamine Antiinfective 117

112 Terbutaline sulfate and guaiphenesinRespiratory System 118

113Terbutaline sulfate, bromohexine HCL and guaiphenesin


114 Tinidazole and clotrimazole Antiinfective 120

115 Tinidazole and norfloxacin Antiinfective 121

116 Tinidazole and ofloxacine Antiinfective 122

117 Tinidazole, doloxanide furoate and furazolidone Antiinfective 123

118 Tinidazole, furazolidine and diloxamide furate Antiinfective 124

119 Triamterene and hydrochlorthiazide CVS 125

120 Trianidine and ibuprofen NSAID 126

121 Trimethoprim and norfloxacin Antiinfective 127

122 Tripolidine HCl and pseudoephedrine HCl Respiratory System 128

123 Triprolidine HCl and phenyl propalamine HCl Respiratory System 129

124 Triprolidine HCl and Pseudoephedrine HCl Respiratory System 130

125 Pseudoephedrine HCl and cetrizineRespiratory System 131

126 Nimusalide and paracetamol NSAID 132

127 Pseudoephedrine HCl and cetrizineRespiratory System 133

128 Nimusalide and diclofenic sodium NSAID 134

129 Gliclazide and rasiglitazone Antidebetics 135

130 Ornidaole and norfloxacine Antiinfective 136

131 Metformine HCl and glinepride Antidebetics 137

132 Amoxicillin trihyderate and metrinidazole Antiinfective 138

Table-3

List of multi-component formulation estimated by high performance liquid

chromatography (HPLC) with respective reported references.


1Acetaminophen, dextrapropoxyphen and oxyphenbutaszone


2 Amilodipin and atenolol CVS 140

3 Amitriptyline HCl and chlordiozepoxide Antidepressant 141

4 Amlodipine and benazepril CVS 142

5 Amoxycillin and clavulanic acid Antiinfective 143

6 Anti-histaminic multi componentRespiratory System 144

7Aspirin-caffeine- butalbital and acetaminophen -caffeine- butalbital NSAID 145

8 Bromohexine HCl and CephalexineRespiratory System 146

9

Bromohexine HCl and methyl and propyl hydroxybenzote and determianation dextromethorphen hydrobromide


10Bromohexine HCl, phnyl praopalamine HCL and Chlorphenaramine meleate


11 Caffeine and paracetamol NSAID 149

12 Ceprofloxacin and tinidazole Antiinfective 150

13 Ciprofloxacin HCl and tinadazole Antiinfective 151

14 Ciprofloxacin HCl and tinidazole Antiinfective 152

15Codeine phosphate, ephedrine HCl and chlorphenaramine maleate


16 Dextromethorphen and pseudo ephedrine Respiratory System 154

17 Diclofenic sodium, paracetamol and chlormerzonone NSAID 155

18 Diloxanide furoate and tinidazole Antiinfective 156

19 Ethniyl estradiol and levonorgestral Endocrine System 157

20 Frusimide and spironolactone CVS 158

21 Guaifenesin and codeine phosphate Respiratory System 159

22Guaifenesine, pseudoephedrine HCl and dextromethorphen hydrobromide


23 Hydrochlorthaizide and losartan potassium CVS 161

24 Ibuprofen and dextromethorphen HCl NSAID 162

25 Lavnivudine and zidovudine Antiinfective 163

26 Metranidazole, clotimazole and chlorhexidne acetate Antiinfective 164

27 Nimuselide and camplofine NSAID 165

28 Norfloxacin and metranidazole Antiinfective 166

29 Paracetamol, caffeine and prophyphenazone NSAID 167

30Paracetamol, chlorphenaramine maleate, phenylepherine and caffeine NSAID 168

31 Propylphenazone and ketoprophen 169

32Pyridoxine HCl, nephazoline nitrate, chlorpheniramine meleate and panthenol


33 Sodium cromoglycate and salbutamol sulfate Respiratory System 171

34 Terbutaline sulfate and guaiphenesinRespiratory System 172

35 Terbutaline, bromohexine and guaiphenesine Respiratory System 173

36 Terbutaline, guaiphenesin and ambroxol Respiratory System 174

37 Theophylline and Phenobarbital Antipsycotic 175

38 Thiophylline and guaifenesinRespiratory System 176

39 Trihexyphenidyl HCl and chlorpromazine HClRespiratory System 177

40 Vitamin A, E, and D3 Multivitamine 178

Table-4

List of multi-component formulation estimated by reversed phase high performance

liquid chromatography (RP-HPLC) with respective reported references.

Sr. NO. Combination of drugs Therapeutic Use Ref. No

1 Amlodipine and benazepril CVS 179

2 Amlodipine and losarton potassium CVS 180

3 Amoxicillin and clavulanate Antiinfective 181

4 Amoxycillin and clavulanate potessium Antiinfective 182

5 Amoxycillin, probencid and tinidazole Antiinfective 183

6 Ampicilline and probencid Antiinfective 184

7 Cefazoline and cefotoxime Antiinfective 185

8 Cefelexine and trimethoprim Antiinfective 186

9 Ceprofloxacine and arnidazole Antiinfective 187

10 Cetrizine and pseudo ephedrine HCl Respiratory System 188

11Chlophenaramine meleate, phenylepherine HCl and caffeine and acetaminophen


12 Cinnarizine and domperidone GIT 190

13 Ciprofloxacin and tinadazole Antiinfective 191

14 Codine phosphate and chlorphenaramine maleate Respiratory System 192

15Codine phosphate, doxylamine succinate, paracetamol and caffeine


16Dextropropoxyphen HCl, diclofenic sodium and paracetamol


17 Domamethasone, p-chlrophenol and thymolRespiratory System 195

18 Domperidon and omeprazole GIT 196

19 Doxylamine succinate and pyridoxine HCl GIT 197

20 Fexofenadine HCl and pseudoephedrine sulphateRespiratory System 198

21 Flucanozole, metranidazole and choramphinicol Antiinfective 199

22 Gilendsmine and metformineHCl Antidibetics 200

23 Gliclazide and metformine HCl Antidibetics 201

24 Glipiozide and metformine HCl Antidibetics 202

25 Glipizide and metformine Antidibetics 203

26 Lasartan potassium and hydrochlothiazide CVS 204

27 Lomefloxacine HCl, prothionamide and pyrizinamide 205

28 Metformine HCl and pigglitazone Antidibetics 206

29 Methocarbamol and nimuselide NSAID 207

30 Methocarbamol, ibuprofen and paracetamol NSAID 208

31 Nicotinic acid and meclozine HCl 209

32 Nimesulide and diclofenic sodium NSAID 210

33 Nimesulide and Tizanidine HCl NSAID 211

34 Nimuselide and chlorzoxazone NSAID 212

35 Norfloxacin and ornidazole Antiinfective 213

36 Ofloxacin and tinidazole Antiinfective 214

37 Ornidaole and ofloxacine Antiinfective 215

38 Paracetamol and Chlormezonon NSAID 216

39 Paracetamol and nimesulide NSAID 217

40 Paracetamol, ibuprophen and methocarbamol NSAID 218

41 Paracetomol and nemuselide NSAID 219

42Phenylpropanolamine HCl, cetrizine diHCl and acetaminophen


43 Picglitazone and metformine Antidebetics 221

44 Pseudoephedrine HCl and loratidine HCl Respiratory System 222

45Pseudoephedrine HCl, dextromethorphen hydrobromide and triprolidone HCl


46 Pyrantel pomoate and mebendazole Antiinfective 224

47 Ramipril and amlodipine CVS 225

48 Ramipril and hydrochlorothiazide CVS 226

49 Ranitidine HCl and domperidom GIT 227

50 Sertraline and alprozalam Antipsycotic 228

51 Tinidazole and furozolidine Antiinfective 229

52 Tizanidine and nimesulide NSAID 230

53 Triamterene and xipamide 231

54 Trianidine, diclofenic and paracetamol NSAID 232

55 Simvastine and nicotinic acid Multivitamine 233

Table-5

List of multi-component formulation estimated by reversed phase high performance

thin layer chromatography (HPTLC) with respective reported references.


1 Cephalexin acid cefadoxil Antiinfective 234

2 Cinnarzine and domperidon maleate GIT 235

3 Gliclazide and metformine HCl Antidibetics 236

4 Gidazide and rosiglitazone Antidibetics 237

5 Lignocaine and phenylephrine HClRespiratory System 238

6 L-lysine HCl and DL- methionone Endocrine System 239

7 Methocarbamol and nimesulide NSAID 240

8 Paracetamol and mefanamic acid NSAID 241

9 Pseudoephedrine sulphate and laratadineRespiratory System 242

10Rifluoperazine HCl, trihexylphenidyl HCl and chlorpromazine HCl


11 Amlodipin and benazepril HCl CVS 244

Table-6

List of multi-component formulation estimated by gas chromatography (GC) with

respective reported references.


1 Acetaminophen, salicylamide, phenyltoloxamine NSAID 245

2 Benazepril HCl and hydrochlorthaizide CVS 246

3 Codeine and ethyl morphine HCl Respiratory System 247

4 Diclofenic sodium and chlorzoxazone NSAID 248

5 Fluoxetine, fluvoxamine and clomipramine Antipsycotic 249

6 Guaifenesin, pseudoephedrine and dextromethorphan Respiratory System 250

7 Oxybenzone and octylmethoxy cinnamate Antiinfective 251

About Authors

S. J. Daharwal*, G. Garg, R. B. Saudagar, S. Saraf and Swarnlata Saraf

* Mr. S.J. Daharwal has nearly 15 years of research and teaching experience. He is a hard

working researcher . Mr . Daharwal did his masters degree from Dept. of Pharmacy, of

Nagpur University. He has over 12 publications to his credit published in international and

national journals. His research interest extends from analytical methods, Drug synthesis and

computer added drug designing. Presently, he is working as a Lecturer at Institute of Pharmacy

Pt. Ravishankar Shukla University, Raipur, (C.G.)

Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur. 492 010. (India) E-

mail:[email protected]

Mr. Gopal Garg has nearly 2 years of research and teaching experience. He is a hard working

researcher. Mr. Garg did his masters degree from Dept. of Pharmacy, Dr. H. S. Gour University,

SAGAR. He has over 7 publications to his credit published in international and national journals.

His research interest extends from Analytical technique to phytochemical estimation.

Presently, he is working as a Lecturer at Institute of pharmacy Pt. Ravishankar Shukla

University, Raipur, (C.G.)

Mr. R. B. Saudagar has nearly 10 years of research and teaching experience. Mr

Saudagar did his masters degree from Dept. of Pharmacy, of SGSITS Indore. He has over 5

publications to his credit published in international and national journals. His research interest

extends from analytical methods, Drug synthesis. Presently, he is working as a Lecturer at

Institute of Pharmacy Pt. Ravishankar Shukla University, Raipur, (C.G.)

Dr. (Mrs). Swarnlata Saraf has nearly 14 years of research and teaching experience. She is

a leading scientist and well-known in the field of herbal Cosmetics. Dr. (Mrs.) Saraf did her

doctoral research at the Dept. of Pharmacy, Dr. H. S. Gour University, SAGAR. She has over 40

publications to her credit published in international and national journals. She is an active

member of IPA ,APTI and ISTE. Her research interest extends from Herbal Cosmetics to

transdermal drug delivery (Iontiphoresis), New Drug Delivery Systems for biological

therapeutic agents. She has Co-authored 1 books, (in press). Presently She is working as a

Reader at Institute of pharmacy Pt. Ravishankar Shukla University,Raipur,(C.G.).

Prof. S. Saraf has nearly 17 years of research and teaching experience at U.G. and P.G. level.

He is a leading scientist and well-known academician . Prof. Saraf did his doctoral research at

the Dept. of Pharmacy, Dr. H. S. Gour University, SAGAR. He has over 50 research publications

to his credit published in international and national journals. He has delivered invited lectures

and chaired many sessions in several National Conferences and Symposia in India. His

research interest extends from Herbal Cosmetics to Herbal drug standardization Modern

analytical techniques, New Drug Delivery Systems with biotechnology bias. He has authored 1

books, in press. Presently, he is Professor and Director Institute of pharmacy and Dean, Faculty

of Technology, Pt. Ravishankar Shukla University , Raipur , (C.G.). E-mail:

[email protected]

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