Methods Of Estimation Of Multi

Methods of estimation of multicomponent formulations: A review in

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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 multicomponents 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 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.

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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UV-

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

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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), 707711. 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

Eicosapentacnoic acid and Decosahexaenoic acidand A-tocopreryl 114 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

Bromohexin HCl, diphenhydronon HCl and 18 guaiphenesin

Respiratory System

24

19 Bromohexine HCl and pseudo ephedrine HCl

Respiratory System

25

Bromohexine HCl, dextromethorphen hydrobromide 20 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

Chloramphinicol and dexamethasone sodium 28 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

Dextromethorphen hydrobromide and Bromohexine 38 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

Hydrochlorthiazide and amiloride HCl or with 53 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

Noscopine, chlorphenaramine maleate and ephedrine 78 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

Phynyl propanalamine, chlorphenaramine and 85 Bromohexine HCl

Respiratory System

91

Phynyl propanalamine, chlorphenaramine malate and 86 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

Pseudo ephedrine HCl, and dextromethorphen 90 hydrobromide

Respiratory System

96

Pseudo ephedrine HCl, dextromethorphen 91 hydrobromide and chlorphenaramine malate

Respiratory System

97

Pseudo ephedrine sulphate, dexbrompheniramine 92 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

Spironalactne with hydrochlorthaizide and 109 spironalactne with frusemide

Diuretics

115

110 Sulfamethoxazole

Antiinfective

116

111 Sulfaquinozaline, sulfamethzine and pyrimethamine

Antiinfective

117

112 Terbutaline sulfate and guaiphenesin

Respiratory System

118

Terbutaline sulfate, bromohexine HCL and 113 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

Acetaminophen, dextrapropoxyphen and 1 oxyphenbutaszone

Therapeutic Use Respiratory System

Ref. No. 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

Aspirin-caffeine- butalbital and acetaminophen 7 -caffeine- butalbital

NSAID

145

8 Bromohexine HCl and Cephalexine

Respiratory System

146

Bromohexine HCl and methyl and propyl hydroxybenzote and determianation dextromethorphen 9 hydrobromide Respiratory System

147

Bromohexine HCl, phnyl praopalamine HCL and 10 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

Codeine phosphate, ephedrine HCl and 15 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

Guaifenesine, pseudoephedrine HCl and 22 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

Paracetamol, chlorphenaramine maleate, 30 phenylepherine and caffeine

NSAID

168

31 Propylphenazone and ketoprophen

169

Pyridoxine HCl, nephazoline nitrate, chlorpheniramine 32 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

Chlophenaramine meleate, phenylepherine HCl and 11 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

Codine phosphate, doxylamine succinate, paracetamol 15 and caffeine Respiratory System

193

Dextropropoxyphen HCl, diclofenic sodium and 16 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

Phenylpropanolamine HCl, cetrizine diHCl and 42 acetaminophen

Respiratory System

220

43 Picglitazone and metformine

Antidebetics

221

44 Pseudoephedrine HCl and loratidine HCl

Respiratory System

222

Pseudoephedrine HCl, dextromethorphen 45 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

Rifluoperazine HCl, trihexylphenidyl HCl and 10 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

* 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) Email:[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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