Stability indicating RP-HPLC method for the determination of Terbutaline sulphate Guaifenesin, Ambroxol hydrochloride and preservatives content in liquid formulations by hanimi

VIEWS: 692 PAGES: 6

More Info
									                             Hanimi Reddy Bapatu et al. / Journal of Pharmacy Research 2011,4(11),4117-4122
Research Article                                           Available online through
ISSN: 0974-6943                                              www.jpronline.info
    Stability indicating RP-HPLC method for the determination of Terbutaline sulphate,
    Guaifenesin, Ambroxol hydrochloride and preservatives content in liquid formulations
                           Hanimi Reddy Bapatu 1*, Maram Ravi Kumar2, Useni Reddy Mallu 3, Hari kishan Reddy Ganthi 3,
                                                Chandra Mohan Rao Kota 4 and Viswanath Reddy Pyreddy 3
                                      1
                                        Department of Chemistry, JNT University, Kukatpally, Hyderabad, AP, India-500072.
                               2
                                 AR&D, Custom Pharmaceutical Services, Dr. Reddys Laboratories Ltd, Bachupally, Hyd-72, India.
                                   3
                                     Department of Chemistry, Sri Krishnadevaraya University, Anantapur, AP, India-515003.
                                        4
                                          Ideal College of Arts and Sciences, Kakinada, East Godhavari, AP, India-533464.
                                    Received on: 19-05-2011; Revised on: 08-06-2011; Accepted on:01-07-2011

                                                                            ABSTRACT
Objective: To develop a single RP-HPLC method for determination of Terbutaline sulphate, Guaifenesin, Ambroxol hydrochloride and preservatives (methyl
paraben and propyl paraben) contents in liquid formulation. Method: Chromatographic separation was achieved on a Sunfire C18, 250 x4.6mm, 5µ column.
Mobile phase composed of Sol-A: phosphate buffer (0.01M Potassium dihydrogen orthophosphate buffer pH 6.0± 0.1) and Sol-B: Acetonitrile with a simple
gradient program (0-5min, sol-A:87-87; 5-10min- sol-A:87-80; 10-20min- sol-A:80-50; 20-25min- sol-A:50-50, 25-30min- sol-A:50-87and 30-35min- sol-
A:87-87). 1.0ml per min flow rate and detection was at 214 nm. Results: High resolution was achieved with the simple gradient program and retention time of
terbutaline sulphate, Guaifenesin, methyl paraben, ambroxol hydrochloride and propyl paraben are about 3.68min, 15.17min, 18.71min, 23.27min and 24.38min,
respectively. The area of all ingredient peaks were a linear function of concentration in the range 98.7 to 296.1 ppm for Ambroxol hydrochloride, 6.2 to 18.6
ppm for Terbutaline Sulphate, 246.4 to 747.3 ppm for Guaifenesin, 44.0 to 136.1 ppm for Methyl paraben and 5.5 to 14.6 ppm for Propyl paraben and the
corelation co-efficient value of all active ingredients within the limit (0.999). Conclusion: Proposed gradient HPLC method was validated with specificity,
linearity, accuracy, reproducibility ruggedness and it is applicable for regular analysis.

Key words:Terbutaline sulphate, Guaifenesin, ambroxol, Methyl paraben, Propyl paraben, Liquid formulations and RP-HPLC method.

INTRODUCTION
Each 5 mL syrup contains
Ambroxol hydrochloride IP       : 20 mg
Terbutaline sulphate IP         : 1.25 mg
Guaiphenesin IP                 : 50 mg

Terbutaline (1-6) is a ß 2-receptor agoinst. It helps the relaxation of the smooth
muscle found principally in bronchial, vascular and uterine tissue; wheezing and
                                                                                     Ambroxol hydrochloride                    Terbutaline sulphate
shortness of breathe troubled breathing caused by asthma, chronic bronchitis,
emphysema and other lung diseases. Terbutaline has little effect on ß 1 receptors;
thus direct cardiovascular stimulation occurs. However, terbutaline should be
used carefully in cats with pre-existing cardiac disease, such as cardiomyopathy.
Terbutaline use during pregnancy is associated with development of autism
in humans. Terbutaline side effects are drowsiness and headaches, increased
heart rate, diabetes, anxiety and worsening breathing problems.

Guaiphenesin is also called as guaifenesin (7-11). It is used to reduce chest con-   Methyl paraben Guaifenesin                              Propyl paraben
gestion caused by the common cold, infections, or allergies, including medical,
veterinary, and personal, women to facilitiate conception by thinning and in-
creasing the amount of cervical mucus, treatment of primary dysmenorrhea .                        Figure-1: Chemical structure of all ingredients
Guaifenesin may cause side effects, headache, nausea and vomiting.                   All ingredients have reported methods for individual and other combination
                                                                                     products (16-18) and there is no method reported for the simultaneous estimation of
Ambroxol is an active mucolytic agent. Ambroxol is used in the treatment of          Terbutaline Sulphate, Guaifenesin, Ambroxol hydrochloride, methyl paraben
respiratory diseases, pain relief in acute sore throat (12-15). Ambroxol is a very   and propyl paraben in combined liquid dosage forms. The objective of the
potent inhibitor of the neuronal Na+ channels.                                       present study is to develop a single RP-HPLC method for the estimation of
                                                                                     Terbutaline Sulphate, Ambroxol hydrochloride, Guaifenesin and preservatives in
Chemical structures of all ingredients were represented in figure-1.All three        liquid formulation.
ingredients are available in liquid pharmaceutical dosage forms.
                                                                                     MATERIALS AND METHODS

*Corresponding author.                                                               Selection of mobile phase:
Hanimi Reddy Bapatu                                                                  Various buffer salts, pH values were tried with different organic solvents (aceto-
H. No: 4-22-51/25,                                                                   nitrile or methanol) for the optimization of mobile phase. Finally well shaped
Koritepadu, Guntur, Pin No: 522 007,                                                 and high resolution was achieved with pH 6.8 phosphate buffer and acetonitrile
Andhra Pradesh, India.                                                               with gradient program.
Tel.: + 91-9490310239
E-mail:hanimi.b@gmail.com
                                                                                     Chemicals and reagents:
                                                                                     Potasssium di hydrogen orthophosphate, triethyl amine (AR Grade) were pro-


                                            Journal of Pharmacy Research Vol.4.Issue 11.November 2011                                                    4117-4122
                                            Hanimi Reddy Bapatu et al. / Journal of Pharmacy Research 2011,4(11),4117-4122
     cured from S.D fine chemicals. High pure (NLT 98.5%) standards (Terbutaline                                   The %RSD of the area of analyte peaks in standard chromatograms should be
     Sulphate, Guaifenesin, ambroxol hydrochloride, methyl paraben and propyl                                      NMT 2.0 %; Theoretical plates of analyte peaks in Standard chromatograms
     paraben) were used for this study. HPLC grade Methanol and acetonitrile were                                  should be NLT 2000; Tailing Factor of analyte peaks in Standard Chromato-
     procured from Spectrochem Pvt. Ltd. Water is prepared by mili Q system                                        grams should be NMT 2.0.
     (Milli-pore).                                                                                                 Calculation:
                                                                                                                   mg/5 ml = Test solution area x Std. Dilution factor x Std. Potency
     Buffer preparation (Mobile Phase-A):                                                                                         Standard solution area x Test dilution factor
     0.01M Potassium dihydrogen orthophosphate buffer adjusted pH 6.0 with Tri-
     ethylamine. Filtered through 0.45µ membrane filter and degassed.                                              % of active =      mg/5 ml x 100_______
                                                                                                                                   Labeled amount in mg / 5 ml
     Mobile phase B: Filtered and degassed Acetonitrile as mobile phase-B.
     Diluent: water and Methanol in the ratio of 50:50 v/v.                                                        RESULTS AND DISCUSSION
     HPLC conditions:
     Column:            Sunfire C18 (250X4.6mm, 5µm)                                                               METHOD DEVELOPMENT
     Wavelength:        214nm                                                                                      All active ingredients have UV activity. All pure standard solutions were pre-
     Injection volume: 10 µL                                                                                       pared with diluent and scanned the UV absorbance from 200nm to 400nm. UV
     Flow rate:         1.0 mL/min                                                                                 spectrums of all ingredients (Source: HPLC/PDA analysis) were represented in
     Temperature:       40°C                                                                                       figure-2. Based on the UV spectrum of all actives, samples absorbance was
     Run time:          35min                                                                                      measured at 214nm. Initial steps in method development trials were performed
     Mobile phase:      Sol-A: Buffer and Sol-B: Acetonitrile                                                      with water and acetonitrile, C8 250mm column but the elution of active peaks
     Gredient program: (0-5min, sol-A:87-87; 5-10min- sol-A:87-80; 10-20min-                                       and separation was poor further trials were done with ammonium acetate and
     sol-A:80-50; 20-25min- sol-A:50-50, 25-30min- sol-A:50-87and 30-35min-                                        perchlorate buffers but the elution of ambroxol and propyl paraben was poor
     sol-A:87-87)                                                                                                  and baseline also not acceptable. Finally, optimized the chromatographic condi-
                                                                                                                   tions with phosphate buffer, acetonitrile, C18, 250x4.6mm, 5µ column and
     Standard Preparation:                                                                                         absorbance was measured at 214nm.
     Prepared the standard solution with high pure standards consist of ambroxol
     200ppm, Terbutaline sulphate 12.5ppm, Guaifenesin 500ppm, methyl paraben                                      System suitability:
     100ppm and propyl paraben 10ppm with diluent.                                                                 The retention times of Terbutaline Sulphate, Guaifenesin, Methyl Paraben,
                                                                                                                   Ambroxol and Propyl Paraben were found at ~ 3.6, 15.1, 18.7, 23.2and 24.3min,
     Sample preparation:                                                                                           respectively. These retention times did not vary to any considerable changes
     Weigh accurately sample quantity equivalent to 5 ml of syrup sample and                                       during the analysis. Percent (%) RSD of five replicate injections of standard
     transfer into a 100 ml volumetric flask. Add 50 ml diluent, sonicate for about 5                              retention time and area were found to be within the limit (%RSD of RT is not
                                                                                                                   more than 1.0% and area is not more than 2.0%). Resolution between all active
            4.283Terbutaline                                                                                       peaks is more than 3.0 (limit is note less than 2.0). Diluent and placebo have no
                                                                                                                   interference with all active peaks. Diluent, standard solution and test solution
     0.05                                                                                                          chromatograms were represented in figure-3 to 6. Table-1 represents the system
AU




                                                 276.8                                                             suitability parameters.
     0.00
            16.433 Ambroxol
                223.5
AU




     1.00
                                                273.2

     0.00
            20.057 Methyl Paraben
                                    255.4
     0.50
AU




     0.00
            24.481 Guaiphenesin
     1.00
                                                                                                                   Figure-3: Diluent chromatogram
AU




     0.50                      247.1
                                                               309.0
     0.00
            26.035 Propyl Paraben
     0.06
                                    255.4
     0.04
AU




     0.02

     0.00
              220.00      240.00       260.00     280.00   300.00     320.00   340.00   360.00   380.00   400.00
                                                                nm
     Figure-2: UV spectrum of all ingredinets
     minutes & make up the volume with diluent. Filter the solution through Whatman
     0.45µ membrane filter paper rejecting first few ml of filtrate. (Concentration of
     Terbutaline in solution is 12.5ppm, Ambroxol is 200ppm, Guaifenesin is 500ppm,
     methyl paraben 100ppm and propyl paraben 10ppm).

     System Suitability:                                                                                           Figure-4: Placebo chromatogram
     System suitability parameters were finalyzed as per ICH and FDA guidelines.

                                                                     Journal of Pharmacy Research Vol.4.Issue 11.November 2011                                                       4117-4122
                                        Hanimi Reddy Bapatu et al. / Journal of Pharmacy Research 2011,4(11),4117-4122
                                                                                                            Specificity
                                                                                                            The specificity of the method has been evaluated with respect to diluent, pla-
                                                                                                            cebo and degradation impurities. Degration studies were performed with acid,
                                                                                                            base, peroxide, water, thermal, sunlight and UV light, results were satisfactory
                                                                                                            and tabulated in table-3. Peak purity also checked for all peaks and found to be
                                                                                                            satisfactory. Peak purity chromatograms were represented in figure-7 and re-
                                                                                                            sults were represented in table-4.

                                                                                                            Table-3: Forced degradation study
                                                                                                            Stress Condition                                  % Degradation
                                                                                                                                            Ambroxol    Terbutaline Guaifenesin Methyl Propyl
                                                                                                                                            HCl         Sulfate                 paraben paraben

                                                                                                            Acid (0.1N HCl,15 min @ 60°C)       6.74    3.77       7.50        0.2     8.67
                                                                                                            Alkali (0.1N NaOH,15 min @ 60°C)    7.95    0.94       10.39       3.97    6.3
                                                                                                            Peroxide (3%H2O2,15min @ 60 °C)     7.95    0.94       11.18       6.31    6.9
                                                                                                            Water (water 15 min @ 60°C)          8.17   7.55       11.89       7.22    8.67
                                                                                                            Thermal (15 min @ 60°C)              9.15   1.89       12.07       6.31    9.85
                                                                                                            Sun-Light (1.2 million Lux hours)    6.54   7.55       9.34        4.29    5.33
                                                                                                            UV-Light (200 watt hours / m 2 )     5.40   6.60       8.10        4.68    6.67
 Figure-5: Standard chromatogram.




 Figure-6: Test solution chromatogram
 Table 1: System suitability
 System Suitability parameter     Observations
 (five replicate injections)      Terbutaline    Guaifenesin          Methyl      Ambroxol        Propyl
                                  Sulphate                            paraben     hydrochloride   paraben

 % RSD                            0.8            1.4                  0.31        0.2             0.30
 Theoretical plates(avg)          17324          253651               222081      182062          283356
 Tailing factor (avg)             1.1            1.0                  1.0         1.0             1.1
 USP Resolution                   NA             89.5                 24.4        27.1            6.1
 Peak area response

 Std. Inj.                        Ambroxol       Terbutaline          Guaifenesin Methyl          Propyl
                                  HCl            sulphate                         paraben         paraben

 1                                8993170        208995               7699035     3108443         309812
 2                                8957507        206121               7665054     3093421         308452
 3                                8978468        208777               7680969     3082145         309541
 4                                8951595        205639               7718547     3091245         307562
 5                                8988266        209297               7925415     3096314         308214
 Average                          8973801        207766               7737804     3094314         308716

 METHOD VALIDATION
 Validation is a process of establishing documented evidence, which provides a
 high degree of assurance that a specific activity will consistently produce a
 desired result or product meeting its predetermined specifications and quality
 characteristics. The method was validated with Linearity, Accuracy, Precision,
 Specificity and Robustness as per ICH and FDA guidelines (19-23).
 Table-2: Method Precision Studies
Sample % Assay of Label content (SET- I: Precision; SET-II: Intermediate precision)
       Ambroxol HCl       Terbutaline sulphate Guaifenesin            Methyl Paraben Propyl paraben
Number SET- I   SET- II SET- I      SET- II SET-I          SET-II     SET-I      SET-II SET-I SET-II

1            99.8    100.2      98.6      97.6    99.5         99.8       99.0     100.7     101.0   98.8
2            99.9    100.3      101.3     99.0    99.9         99.7       99.1     100.7     97.7    98.6
3            99.9    100.0      99.8      98.5    99.9         99.4       98.9     100.2     98.9    99.7
4            99.9    100.6      99.7      99.9    99.5         99.6       99.0     100.8     98.4    99.5
5            100.0   100.1      100.5     99.4    100.4        99.1       99.5     100.8     98.5    99.4
6            99.8    100.2      99.3      99.4    99.9         98.9       100.2    100.8     97.9    99.0
Average      99.9    100.2      99.9      99.0    99.9         99.4       99.3     100.7     98.7    99.2
Average      100.1              99.4              99.6                    100.0              99.0
 % RSD       0.2                1.0               0.4                     0.8                0.9

 Precision
 Method precision was evaluated by six separately prepared samples of the same
 batch of syrup and injected. Results were found to be satisfactory. Precision (set-                                       Figure-7: Peak purity graphs of all active peaks
 I) and intermediate precision (set-II) results were tabulated in table-2.

                                                          Journal of Pharmacy Research Vol.4.Issue 11.November 2011                                                                    4117-4122
                            Hanimi Reddy Bapatu et al. / Journal of Pharmacy Research 2011,4(11),4117-4122
Table-4: Peak purity results of all active peaks
 Ambroxol               Acid (0.1N HCl,     Alkali (0.1N NaOH,   Peroxide          Water            Thermal           Sun-Light        UV-Light
 hydrochloride          15 min @ 60°C)      15 min @ 60°C)       (3%H2O2,15min     15 min @ 60°C)   (15 min @60°C)    (1.2 million     (200 watt hr/m 2 )
                                                                 @ 60 °C)                                             Lux hours)

 Purity-1 Angle         0.08                0.095                0.096             0.091            0.094             0.330            0.355
 Purity-1 Threshold     0.260               0.263                0.265             0.266            0.267             0.943            0.990
 Peak purity            Pass                Pass                 Pass              Pass             Pass              Pass             Pass


 Terbutaline sulphate   Acid (0.1N HCl,15   Alkali (0.1N NaOH,   Peroxide (3%H2O2, Water (water     Thermal           Sun-Light        UV-Light
                        min @ 60°C)         15 min @ 60°C)       15min @ 60 °C)    15 min @ 60°C)   (15 min @ 60°C)   (1.2 million     (200 watt hr/m 2 )
                                                                                                                      Lux hours)

 Purity-1 Angle         0.162               0.186                0.157             0.302            0.154             0.169            0.175
 Purity-1 Threshold     0.295               0.286                0.299             0.333            0.303             0.242            0.240
 Peak purity            Pass                Pass                 Pass              Pass             Pass              Pass             Pass

 Guaifenesin            Acid (0.1N HCl,1    Alkali (0.1N NaOH,   Peroxide (3%H2O2, Water (water     Thermal           Sun-Light        UV-Light
                        5 min @             15 min @             15min @           15 min @         (15 min @         (1.2 million Lux (200 watt
                        60°C)               60°C)                60 °C)            60°C)            60°C)             hours)           hr/m 2 )

 Purity-1 Angle         0.184               0.138                0.200             0.196            0.166             0.163            0.261
 Purity-1 Threshold     0.234               0.233                0.234             0.237            0.235             0.259            0.269
 Peak purity            Pass                Pass                 Pass              Pass             Pass              Pass             Pass

 Methyl Paraben         Acid (0.1N HCl,     Alkali               Peroxide          Water            Thermal           Sun-Light        UV-Light
                                            (0.1N NaOH,          (3%H2O2,                           (15 min @ 60°C)   (1.2 million     (200 watt
                        15 min @ 60°C)      15 min @ 60°C)       15min @ 60 °C)    15 min @ 60°C)                     Lux hours)       hr/m 2 )

 Purity-1 Angle         0.047               0.048                0.047             0.059            0.067             0.055            0.059
 Purity-1 Threshold     0.221               0.223                0.224             0.228            0.227             0.250            0.251
 Peak purity            Pass                Pass                 Pass              Pass             Pass              Pass             Pass

 Propyl Paraben         Acid (0.1N HCl,     Alkali (0.1N NaOH,   Peroxide (3%H2O2, Water (water     Thermal           Sun-Light        UV-Light
                        15 min @ 60°C)      15 min @ 60°C)       15min @ 60 °C)    15 min @ 60°C)   (15 min @ 60°C)   (1.2 million     (200 watt hr/m 2 )
                                                                                                                      Lux hours)

 Purity-1 Angle         0.125               0.183                0.239             0.199            0.192             0.124            0.178
 Purity-1Threshold      0.242               0.238                0.248             0.266            0.259             0.215            0.214
 Peak purity            Pass                Pass                 Pass              Pass             Pass              Pass             Pass




                                                                 Figure-8: Overlaid chromatograms of linearity solutions
                                                    Journal of Pharmacy Research Vol.4.Issue 11.November 2011                                               4117-4122
                                        Hanimi Reddy Bapatu et al. / Journal of Pharmacy Research 2011,4(11),4117-4122
 Linearity:
 Linearity solutions were prepared from stock solution at six concentration                          were within the limit 100 ±2.5%. These recovery results reveals that developed
 levels from 50 to 150% of analyte concentrations (98.7 to 296.1 ppm for                             RP-HPLC method can determine Terbutaline Sulphate, Guaifenesin, Ambroxol
 Ambroxol hydrochloride, 6.2 to 18.6 ppm for Terbutaline Sulphate, 246.4 to                          HCl, methyl paraben and propyl paraben. Recovery results were tabulated in
 747.3 ppm for Guaifenesin, 44.0 to 136.1 ppm for Methyl paraben and 5.5 to                          table-6.
 14.6 ppm for Propyl paraben). The linear regression analysis of Ambroxol
 hydrochloride, Terbutaline Sulphate, Guaifenesin, Methyl paraben and Propyl                         Ruggedness and Robustness:
 paraben were constructed by plotting the peak area of the analytes (y) versus                       Ruggedness of the method was validated by using different analysts, instruments
 analytes concentration in (x) axis. The calibration curves were linear in the                       and columns with same experimental conditions these results were tabulated in
 range of 98.7 to 296.1 ppm for Ambroxol hydrochloride, 6.3 to 18.6 ppm for                          table-2. Robustness of the method was studied by changes in experimental
 Terbutaline Sulphate, 246.4 to 747.3 ppm for Guaifenesin, 44.0 to 136.1 ppm                         conditions like pH, flow rate, temperature. The most important aspect of
 for Methyl paraben and 5.5 to 14.6 ppm for Propyl paraben a correlation                             robustness is to allow for expected variations in method parameters. According
 coefficient of more than 0.999 for all the three drugs. The slope, Y-intercept                      to ICH guidelines, robustness should be considered early in the development
 and correlation coefficient were calculated and summarized in Table-5. Overlaid                     stage of a method. The typical variations studied under this parameter are Flow
 chromatograms of the all linearity solutions were represented in figure-8.                          rate, Wavelength, Mobile phase composition, Temperature, pH of the mobile
  Table-5: Linearity Results                                                                         phase. Table-7 represents the robustness results.

Linearity Results
            Ambroxol HCl         Terbutaline sulphate Guaifenesin        Methyl Paraben     Propyl paraben             CONCLUSION
Level       Conc   Area          Conc      Area      Conc    Area        Conc     Area      Conc      Area             The complete study results reveals that the developed and vali-
            (ppm)                (ppm)               (ppm)               (ppm)              (ppm)                      dated RP-HPLC method is accurate, precise, robust and stability
1 (50%)      98.7     4516957    6.2        109932   246.4    3986794    44.0     1556601   5.5        201017          indicating. This method has wide applicability for preservatives
2 (80%)      157.9    7163944    9.9        170137   397.5    6209405    80.1     2574380   7.0        253005          such as methyl paraben and propyl paraben and useful for regular
3 (100%) 197.4        8976039    12.4       215433   496.9    7744331    100.1    3088601   9.6        328887
4 (110%) 217.1        9855655    13.6       239655   548.5    8531503    110.1    3447198   10.6       366570          quality control analysis of formulation samples.
5 (120%) 236.9        10776103   14.9       264855   596.2    9277393    120.1    3652614   11.6       402909
6 (150%) 296.1        13312612   18.6       321265   747.3    11571142   136.1    4115342   14.6       490836
Correlation
Coefficient: 0.9999              0.9991              0.9999              0.9995             0.9994


 Table-6: Accuracy results                                                                                               Table-7: Robustness results
                      Ambroxol hydrochloride                                                  Sr.        System           Active names     Variations system suitability results                 Limits
   Level          Qty Added Qty Recovered %                   Mean       % RSD                No.        Suitability                       Flow Rate        Temp                Buffer Conc’n
                  (ppm)      (ppm)           Recovery         Recovery                                   parameter                         (0.9 to1.1       (35 to45°C)         (±5%)
                                                              (%)                                                                          mL/min)

   50%             98.7506       99.6746         100.9        101.1      0.2                  1          The % RSD       Ambroxol HCl         0.2-0.5       0.1-0.6       1.1-1.4               NMT 2.0
                   98.7506       99.9734         101.2                                                                   Terbutaline Sulphate 0.8-1.8       0.4-0.8       0.7-1.5
                   98.7506       99.9449         101.2                                                                   Guaifenesin          0.6-1.4       0.5-1.6       0.9-1.9
   100%            197.5012      197.1341        99.8         99.9       0.1                                             Methyl paraben       0.3-0.8       0.1-0.0       1.3-1.2
                   197.5012      197.3208        99.9                                                                    Propyl paraben       0.7-1.5       0.4-1.5       0.8-1.0
                   197.5012      197.3213        99.9                                         2       Tailing factor      Ambroxol HCl        1.0-1.7       1.0-1.4       1.1-1.1               NMT 2.0
   150%            294.2768      289.1785        98.3         98.3       0.0                                             Terbutaline Sulphate 1.1-1.5       1.1-1.4       1.2-1.1
                   294.2768      289.1706        98.3                                                                    Guaifenesin          1.0-1.5       1.0-1.2       0.9-0.9
                   294.2768      289.1754        98.3                                                                    Methyl paraben       1.7-1.2       1.4-1.4       1.1-1.1
   Terbutaline sulphate                                                                                                  Propyl paraben       1.7-1.1       1.3-0.8       1.0-1.0
   50%             6.5203        6.4654          99.2         100.7      1.3                  3       Theoretical plates   Ambroxol HCl      72324-182062 90269-182062 184299-181576            NLT 2000
                   6.5203        6.6149          101.5                                                                   Terbutaline Sulphate 8673-17324    7682-17324    16446-16995
                   6.5203        6.6089          101.4                                                                   Guaifenesin          96478-253651  142821-253651 140082-144252
   100%            13.0406       12.8607         98.6         99.9       1.4                                             Methyl paraben       94086-156986  139632-130733 205329-19896
                   13.0406       13.2047         101.3                                                                   Propyl paraben       102019-211064 180800-30407  155298-145938
                   13.0406       13.0171         99.8
   150%            19.2504       19.0878         99.2         99.7       0.5
                   19.2504       19.2766         100.1
                   19.2504       19.2108         99.8
   Guaifenesin
   50%             249.8590      251.2659        100.6        101.3      0.6                         REFERENCES
                   249.8590      254.2009        101.7                                                    1.     R Ellul-Micallef, Effect of terbutaline sulphate in chronic allergic cough, British
                   257.7910      262.1058        101.7                                                           Medical Journal, 1983, 287 (6397), 940-943.
   100%            495.7520      493.4650        99.5         99.8       0.2                              2.     Rau HL, Aroor AR and PG Rao, Fluorimetric estimation of terbutaline sulphate in
                   495.7520      495.1577        99.9
                   495.7520      495.4416        99.9                                                            dosage forms, Inidan Journal of Pharmaceutical Sciences, 1990, 52 (5), 255-256.
   150%            745.6110      751.8942        100.8        101.6      0.7                              3.     Hultquist C, Wollmer P, Eklundh G, Jonson B, Effect of inhaled terbutaline sulphate
                   745.6110      760.7437        102.0                                                           in relation to its deposition in the lungs, Pulmonary Pharmacology, 1992, 5 (2), 127-
                   745.6110      760.8692        102.0
   Methyl Paraben                                                                                                132.
   50%             50.1046       49.9319         99.7         99.5       0.2                              4.     Newman SP, Morén F, Trofast E, Talaee N and SW Clarke , Deposition and clinical
                   50.1046       49.8573         99.5                                                            efficacy of terbutaline sulphate from Turbuhaler, a new multi-dose powder inhaler,
                   50.1046       49.7651         99.3                                                            The European Respiratory Journal, 1989, 2 (3), 247-252.
   100%            100.2092      99.2224         99.0         99.0       0.1
                   100.2092      99.2641         99.1                                                     5.     Pramod K and HG Shivakumar, Novel core in cup buccoadhesive system and films
                   100.2092      99.0638         98.9                                                            of Terbutaline Sulphate–development and in vitro evaluation, Asian Journal of phar-
   150%            150.3139      150.9569        100.4        101.0      0.5                                     maceutical Science, 2006, 175-187.
                   150.3139      151.8228        101.0
                   150.3139      152.5114        101.5                                                    6.     Lotufo JP, Ejzenberg B, Vieira S, Mukai L, Macedo H, Yamashita C, Ventura G, Baldacci
   Propyl Paraben                                                                                                ER, Okay Y, Continuous nebulization with terbutaline sulfate under tent inhala-
   50%             5.0533        5.0531          100.0        98.1       1.7                                     tion, evaluation of the efficacy in children 2 to 5 years of age in asthmatic crises,
                   5.0533        4.9097          97.2                                                            Revue De Maladies Respiratories, 1998, 15 (3), 255-261.
                   5.0533        4.9038          97.0
   100%            10.1065       10.2098         101.0        99.2       1.7                              7.     Guaifenesin, Drugs.com. http://www.drugs.com/ppa/Guaifenesin-glyceryl-
                   10.1065       9.8697          97.7                                                            guaiacolate.html. Retrieved 2008-10-29 john.
                   10.1065       9.9946          98.9                                                     8.     Gutierrez K, Pharmacotherapeutics: Clinical Reasoning in Primary Care. W.B.
   150%            14.6545       14.5565         99.3         99.1       0.6
                   14.6545       14.5888         99.6                                                            Saunders Co, 2007.
                   14.6545       14.4369         98.5                                                     9.     Goldstein, Jacob, FDA Bumps Phlegm-Fighters From Market, The Wall Street Jour-
                                                                                                                 nal, 2007.
 Accuracy                                                                                                 10.    Marsden JS, Strickland CD, Clements TL, Guaifenesin as a treatment for primary
 Accuracy of the method was studied by recovery evaluation. Known concentra-
                                                                                                                 dysmenorrhea, J Am Board Fam Pract, 2004, 17 (4), 240–246.
 tion of each active ingredient and preservatives was spiked in to separate 50 ml                         11.    Smith SM, Schroeder K, Fahey T, Over-the-counter medications for acute cough in
 aliquots of placebo solution to give mixture solutions of approximately 50, 100                                 children and adults in ambulatory settings, Cochrane Database Syst Rev, 2008.
 and 150 % of stated standard concentration. These samples were analyzed                                  12.    Kido H et al. Secretory leukoprotease inhibitor and pulmonary surfactant serve as
 according to procedure and percentage recoveries calculated. For all analytes at                                principal defenses against influenza A virus infection in the airway and chemical
 the different concentration levels (50, 100 and 150 %), the recovery values

                                                         Journal of Pharmacy Research Vol.4.Issue 11.November 2011                                                                    4117-4122
                      Hanimi Reddy Bapatu et al. / Journal of Pharmacy Research 2011,4(11),4117-4122
      agents up-regulating their levels may have therapeutic potential. Biol Chem 2004;           search, 2011, 2 (2), 121-130.
      385: 1029-1034                                                                        18.   Prasanthi NL et al., Estimation of Ambroxol HCl and Guaiphenisin in tablet dosage
13.   Weiser T, Comparison of the effects of four Na+ channel analgesics on TTX-resistant         form by simultaneous equation method, International Journal of Research in Ayurveda
      Na+ currents in rat sensory neurons and recombinant Nav1.2 channels. Neurosci               and Pharmacy, 2010, 1 (1)140-146.
      Lett. 2006; 395: 179 – 184                                                            19.   International Conference on Harmonization, Q2A: Text on Validation of Analytical
14.   Malerba and Ragnoli, Ambroxol in the 21st century: pharmacological and clinical             Procedures, Federal Register, 1995, 60 (40), 11260–11262.
      update. Expert Opin Drug Metab Toxicol 2008; 4(8): 1119-1129.                         20.   FDA, Analytical Procedures and Methods Validation: Chemistry, Manufacturing
15.   Mostafa Yakoot, Amel Salem, Abdel-Mohsen Omar, Clinical efficacy of farcosolvin             and Controls Documentation, Availability, Federal Register (Notices), 2000, 65(169),
      syrup (ambroxol–theophylline–Guaifenesin mixture) in the treatment of acute exac-           52776–52777.
      erbation of chronic bronchitis, International Journal of Chronic Obstructive Pulmo-   21.   International Conference on Harmonization, Q2B: Validation of Analytical Proce-
      nary Disease, 2010, 5, 251–256.                                                             dures: Methodology and Availability, Federal Register, 1997, 62 (96), 27463–
16.   Senthilraja M and P Giriraj, Reverse phase HPLC method for the simultaneous esti-           27467.
      mation of terbutaline sulphate, bromohexine HCl and Guaifenesin in cough syrup,       22.   USP 25–NF 20, Validation of Compendial Methods Section (1225) (United States
      Asian Journal of Pharmaceutical and Clinical Research, 2011, 4 (2), 13-15.                  Pharmacopeal Convention, Rockville, Maryland, USA, 2002), 2256.
17.   Mohamed A Korany et al., High performance liquid chromatographic determination        23.   www.fda.gov/cder/guidance/cmc3.pdf
      of some Guaifenesin containing cough cold preparations, Journal of Advanced Re-

                                            Source of support: Nil, Conflict of interest: None Declared




                                             Journal of Pharmacy Research Vol.4.Issue 11.November 2011                                                               4117-4122

								
To top