Methods of estimation of multi-component formulations: A review

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Mr. S.J. Daharwal
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 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 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 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 500 C. Also heat (600C) 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.

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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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’; Talanta, 2000, 51(2), 269-279.

99.  Sharma A. K. and Gangwal S.; ‘Simultaneous determination of pseudo mefanamic acid and paracetamol in combined pharmaceutical dosage form’; Indian J. Pharm. Sci., 1996, 58(5), 216-218.

100.          J. J. Berzas Nevado; J. A. Murillio Pulgarin; J. Amador- Hernandez; M. A. Gomez Langue; ‘Simultaneous fluorimetric determination of pyridoxal , pyridoxamine and pyridoxic acid by partial least square using nonlinear variable angle synchronous spectra’; The Analyst 123 (3), 1998, 483-488.

101. Kuchekar B. S.; Thakar S. V.; Hirmath M. R.; Chothe P. P. and Shinde D. B.; ‘Simultaneous estimation of pyridoxine HCl and metformin HCl in combined dosage form’; Indian J. Pharm. Sci., 2002, 64(2), 158-160.

102. Goicocchee H. C. and Oliveri A. C.; ‘Simultaneous determination of rifampicin , pyrizinamide and isoniazide in tablet preparation by multi variate spectrophotometric calibration ’; J. Pharm. Biomed. Anal., 1999, 20(4), 681-686.

103. Rote A. R. and Sharma A. K.; ‘Spectrophotometric determination of rifampicin , pyrizinamide and isoniazide in combined dosage form’; Indian J. Pharm. Sci., 1996, 58(5), 207-210.

104. Rote A. R. and Sharma A. K.; ‘Simultaneous sectrophotometric determination of rifampicin, pyrizinamide and isoniazide by first derivative UV-spectrophotometery in combined dosage form’; Indian J. Pharm. Sci., 1997, 59(3), 119-123.

105. Goyal P.; Pandey S. and Udupa N.; ‘Simultaneous spectrophotometric estimation of rifampicin and isoniazide from combined dosage form’; Indian J. Pharm. Sci., 2002, 64(1), 76-78.

106. Manna A.; Ghosh I.; Sharmishtha D.; Ghosh P. K.; Ghosh L. K.; ‘Simultaneous estimation of rifampicin and isoniazide from combined dosage form’; Indian J. Pharm. Sci., 2000, 62(3), 185-186.

107. Kasture A. V.; Wadodokar S. G. and Kakade R. B.; ‘Spectrophotometric determination of rifampicin and isoniazide in pharmaceutical preparation’; Indian J. Pharm. Sci., 2002, 64(1), 24-27.

108. Manna A.; Ghosh I.; Datta S.; Gupta B. K.; Ghosh P. K.; Ghosh L. K.; ‘Development of a novel method for simultaneous estimation of rifampicin and isoniazide in their combined 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 combination of secobarbital sodium and amobarbital sodium in dosage form’; Indian Drugs, 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 form’; Indian Drugs, 1998, 35(7), 412-414.

115. Bharathi A.; Parimoo P. and Padama K.; ‘Determination of spironalactne with hydrochlorthaizide and spironalactne with frusemide in combination formulation by UV-spectroscopic method’; Indian J. Pharm. Sci., 1995, 57(3), 126-129.

116. Liu, Tian-hu; Zhou, Mingdo; ‘Simultaneous sectrophotometric determination of two component in compound sulfamethoxazole by flexible tolerence simplex method’; Through Chemical Abstract, 2000,132/ 227561b.

117. Berzas; Nevodo, J. J.; Castaneda Penalvo G. and Guzman Bernardo F. J.; ‘Simultaneous determination of sulfaquinozaline, sulfamethzine and pyrimethamine by liquid chromatography ’; J. Chrmatogrp. Sci., 2000,870(1+2), 169-177.

118. Garg R.; Gupta A. and Sharma A. K.; ‘Simultaneous determination of terbutaline sulfate and guaiphenesin’; Indian J. Pharm. Sci., 1998, 60(6), 407-408.

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 triamterene and hydrochlorthiazide in triamterene-H tablet multivariate calibration method’; J. Pharm. Biomed. Anal., 2001, 26(2), 273-279.

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 of nimusilide and diclofenic sodium in tablet dosage form’; Indian Drugs, 2003, 41(2), 108-109.

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 Congress Scientific Abstract, 2003/ GP-46.

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 method and HPLC applied to simultaneous analysis of caffeine and paracetamol in tablet’; J. Pharm. Biomed. Anal., 1999,21 (4), 723-730.

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. Lett., 2000,33(5),869-880.

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 Congress Scientific Abstract, 2003/ GP-28.

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 form’; Indian Drugs, 2002, 39(8), 441-445.

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 Congress Scientific Abstract, 2003/ GP-16.

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 Pharmaceutical Congress Scientific Abstract, 2003/ GP-50.

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 Congress Scientific Abstract, 2003/ GP-24.

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 Pharmaceutical Congress Scientific Abstract, 2003/ GP-49.

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 andDextromethorphen

Respiratory System

21

Terfinidine andDextromethorphen

Respiratory System

22

Bromohexine HCl and guaiphenesin and Salbutamol and Menthol

Respiratory System

23

Ambroxol and guaiphenesin and Salbutamol and Menthol

Respiratory System

24

Lorotadine and Psudeoephdrine HCl

Respiratory System

25

Ambroxol and Psudeoephdrine HCl

Respiratory System

26

Terfinidine, Psudeoephdrine HCl

Respiratory System

28

Neomycin, Bacitracin and Sufacetamide

Topical intiinfective

29

Tolnaftate, Chlorhexidine and Salicylic acid

Topical Antifungal

30

Quiniodochlor and Hydrocortison

Topical Antifungal

31

Beclomethasone, Neomycine and Clotrimazole

Topical Antifungal

32

Beclomethasone, gentamycine and Clotrimazole

Topical Antifungal

33

Beclomethasone, Neomycine and Econozole

Topical 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 Methyltestosterone

Endocrine System

101

Ethinyloestradiol and Desogestrol

Endocrine 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

114

Eicosapentacnoic acid and Decosahexaenoic acidand A-tocopreryl acetated

Hypolipid

115

Ibuprofen and colchicine

Drugs used in gout

116

Chlorphenaramine maleateand Trithioparamethoxy phenyl propene

Allergy & 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

18

Bromohexin HCl, diphenhydronon HCl and guaiphenesin

Respiratory System

24

19

 Bromohexine HCl and pseudo ephedrine HCl

Respiratory System

25

20

Bromohexine HCl, dextromethorphen hydrobromide and chlorphenaramine malate

Respiratory System

26

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

28

Chloramphinicol 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

38

Dextromethorphen hydrobromide and Bromohexine HCl

Respiratory System

44

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

53

Hydrochlorthiazide 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

76

Norfloxacin and tinidazole

Antiinfective

82

77

Norfloxacin and tinidazole

Antiinfective

83

78

Noscopine, chlorphenaramine maleate and ephedrine HCl

Respiratory System

84

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

85

Phynyl propanalamine, chlorphenaramine and Bromohexine HCl

Respiratory System

91

86

Phynyl propanalamine, chlorphenaramine malate and dextromethorphen hydrobromide

Respiratory System

92

87

 Propranolol HCl and hydrochlorthiazide

CVS

93

88

 Propranolol HCl-diazepam

CVS

94

89

Pseudo ephedrine HCl and ibuprofen

NSAID

95

90

Pseudo ephedrine HCl, and dextromethorphen hydrobromide

Respiratory System

96

91

Pseudo ephedrine HCl, dextromethorphen hydrobromide and chlorphenaramine malate

Respiratory System

97

92

Pseudo ephedrine sulphate, dexbrompheniramine melete and loratadine

Respiratory System

98

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

97

Rifampicin, pyrizinamide and isoniazide

Antiinfective

103

98

Rifampicin, pyrizinamide and isoniazide

Antiinfective

104

99

Rifampicin and isoniazide

Antiinfective

105

100

Rifampicin and isoniazide

Antiinfective

106

101

Rifampicin and isoniazide

Antiinfective

107

102

Rifampicin and isoniazide

Antiinfective

108

103

Salbutamol and Bromohexine HCl

Respiratory System

109

104

Salbutamol and etofyllin

Respiratory 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

109

Spironalactne with hydrochlorthaizide and spironalactne with frusemide

Diuretics

115

110

Sulfamethoxazole

Antiinfective

116

111

Sulfaquinozaline, sulfamethzine and pyrimethamine

Antiinfective

117

112

Terbutaline sulfate and guaiphenesin

Respiratory System

118

113

Terbutaline sulfate, bromohexine HCL and guaiphenesin

Respiratory System

119

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 cetrizine

Respiratory System

131

126

Nimusalide and paracetamol

NSAID

132

127

Pseudoephedrine HCl and cetrizine

Respiratory 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.

Sr. NO.

Combination of drugs

Therapeutic Use

Ref. No.

1

Acetaminophen, dextrapropoxyphen and oxyphenbutaszone

Respiratory System

139

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 component

Respiratory System

144

7

Aspirin-caffeine- butalbital and acetaminophen -caffeine- butalbital

NSAID

145

8

Bromohexine HCl and Cephalexine

Respiratory System

146

9

Bromohexine HCl and methyl and propyl hydroxybenzote and determianation dextromethorphen hydrobromide

Respiratory System

147

10

Bromohexine HCl, phnyl praopalamine HCL and Chlorphenaramine meleate

Respiratory System

148

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

15

Codeine phosphate, ephedrine HCl and chlorphenaramine maleate

Respiratory System

153

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

22

Guaifenesine, pseudoephedrine HCl and dextromethorphen hydrobromide

Respiratory System

160

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

30

Paracetamol, chlorphenaramine maleate, phenylepherine and caffeine

NSAID

168

31

Propylphenazone and ketoprophen

 

169

32

Pyridoxine HCl, nephazoline nitrate, chlorpheniramine meleate and panthenol

Respiratory System

170

33

Sodium cromoglycate and salbutamol sulfate

Respiratory System

171

34

Terbutaline sulfate and guaiphenesin

Respiratory 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 guaifenesin

Respiratory System

176

39

Trihexyphenidyl HCl and chlorpromazine HCl

Respiratory 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

11

Chlophenaramine meleate, phenylepherine HCl and caffeine and acetaminophen

Respiratory System

189

12

Cinnarizine and domperidone

GIT

190

13

Ciprofloxacin and tinadazole

Antiinfective

191

14

Codine phosphate and chlorphenaramine maleate

Respiratory System

192

15

Codine phosphate, doxylamine succinate, paracetamol and caffeine

Respiratory System

193

16

Dextropropoxyphen HCl, diclofenic sodium and paracetamol

Respiratory System

194

17

Domamethasone, p-chlrophenol and thymol

Respiratory System

195

18

Domperidon and omeprazole

GIT

196

19

Doxylamine succinate and pyridoxine HCl

GIT

197

20

Fexofenadine HCl and pseudoephedrine sulphate

Respiratory 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

42

Phenylpropanolamine HCl, cetrizine diHCl and acetaminophen

Respiratory System

220

43

 Picglitazone and metformine

Antidebetics

221

44

Pseudoephedrine HCl and loratidine HCl

Respiratory System

222

45

Pseudoephedrine HCl, dextromethorphen hydrobromide and triprolidone HCl

Respiratory System

223

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.

Sr. NO.

Combination of drugs

Therapeutic Use

Ref. No.

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 HCl

Respiratory 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 laratadine

Respiratory System

242

10

Rifluoperazine HCl, trihexylphenidyl HCl and chlorpromazine HCl

Respiratory System

243

11

Amlodipin and benazepril HCl

CVS

244

Table-6

List of multi-component formulation estimated by gas chromatography (GC) with respective reported references.

Sr. NO.

Combination of drugs

Therapeutic Use

Ref. No.

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

Image

* 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:daharwalresearch@rediffmail.com

Gopal garg

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.)

Swarnlata Saraf

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: shailendrasaraf@rediffmail.com

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