Research Articles

2018  |  Vol: 4(3)  |  Issue: 3(May-June)  |  https://doi.org/10.31024/ajpp.2018.4.3.9

Validation and comparative electrochemical analysis of aspirin in formulation


Nilanjan Samanta, Rumiya Biswas, Susmita Pal, Anindya Bagchi*, Prosenjit Mukherjee, Anusree Raha, Monit Pal, Abhik Si

Netaji Subhas Chandra Bose Institute of Pharmacy, Chakdaha, Nadia, Westbengal, India.

*Corresponding Author

Anindya Bagchi

Assistant Professor

Netaji Subhas Chandra Bose Institute of Pharmacy, West Bengal, India


Abstract

Objective: The objective of the work is to develop a simple precise, rapid accurate, sensitive and comparative electrochemical titrimetric method for quantitative determination of aspirin in pharmaceutical dosage form. Material and methods: The titration was carried out using standardized 0.1 M sodium hydroxide against formulated aspirin sample and all the results were statistically validated. Here Potentiometric and Conductometric titration method were used. Results and Discussion: The proposed potentiometric method was found to be precise with % RSD <1 (n = 5) as the method showed strict linearity (r2 > 0.99) in between 100-200 mg of drug substance weight. The percentage recovery of aspirin in the optimized method was found to be lies in between 97 % to 101 %. The proposed conductometric method was found to be precise with % RSD >1 (n = 6). The method showed strict linearity (r2 > 0.99) between 100-200 mg of drug substance weight. The percentage recovery of aspirin in the optimized method was almost 100% to the corresponding 100 and 300 mg of the drug. Conclusion: Potentiometric method was seems to have more effective one rather than the conductometric method one as aspirin can be assayed electrochemically with in concentration range with this validated method that was optimized without the effect of excipients.

KeywordsValidation, Titration, Potentiometric method, Conductometric method, precision, Percentage recovery


Introduction

Aspirin, also known as acetylsalicylic acid (ASA), is a medication used to treat pain, fever, or inflammation. In potentiometric titration the potential of an indicator electrode is measured as a function of the volume of titrant added. The equivalence point of the reaction will be reach by a sudden change in potential in a plot of e.m.f reading against the volume of titrant solution. In this method a pH meter can be used having an indicator electrode or glass electrode (give reference). The electrical current through a chemical cell is carried out by the ionic species in the solution conductometrically. The ease with which current is conducted through a solution (under the influence of potential difference applied across two electrodes) is mainly depends upon the concentrations and kind of ions in the solution. If two suitable electrodes are present in a solution and potential difference is applied across those electrodes then current will flow through the solution. During progress of a conductometric titration changes in the conductivity of the solution usually occur and at the end point involving neutralization or precipitation reaction the conductivity of the solution will be minimum. The equivalence point may be located graphically by plotting the change in conductance as a function of the volume of titrant added. The term 'titrimetric analysis' or volumetric analysis refers to quantitative chemical analysis carried out by determining the volume of a solution of accurately known concentration which is required to react quantitatively with a measured volume of a solution of the substance to be determined (Bagchi et. al., 2016).

In this study the comparative electrochemical method was developed by using linearity, accuracy and precision as parameters which were statistically validated.

Chemical assay

A chemical assay, as studied under the branch of chemistry called analytical chemistry, is divided into qualitative (identity) analysis and quantitative (amount of substance) analysis. Some of the methods used in qualitative analysis include extraction, distillation, precipitation and other methods that determine physical and chemical properties. Quantitative analysis involves the measurement of the isolated volume or weight of the substance. A chemical assay also utilizes instruments and techniques, such as spectroscopy, chromatography and electrophoresis, to measure the physical quantities of the analyte.

Validation Parameters - Assays

USP General Chapter 1225, as well as the ICH Guideline for Industry (Text on Analytical Procedures), provide cursory descriptions of typical validation parameters, how they are determined, and which subset of each parameter is required to demonstrate validity, based on the method's intended use. For example, it would be inappropriate to determine limits of detection or quantisation for an active ingredient using an assay method intended for finished product release. However, if the method was intended to detect trace quantities of the active ingredient for purposes of a cleaning validation study, then knowledge of the detection and quantification limits are appropriate and necessary. For this reason, validation of each assay or test method should be performed on a case-by-case basis, to ensure that the parameters are appropriate for the method's intended use. This is even more important when validating stability-indicating assay methods, because these validations are more complex - for example, they may require forced degradation, samples spiked with known degrades, literature searches, etc.

Material and methods

Materials

Potassium Hydrogen Phthalate and Ethanol were required and it was purchased from Merck India Pvt. Ltd. Also Sodium hydroxide was required as it was purchased from Loba Chem Pvt. Ltd. Dilution has been carried by using ethanol.

Instrument and Apparatus required

A GOLD model 533 pH meter with Glass electrode and a simple weight machine from EAGLE were used. From the instrument the potential reading was noted which having the unit called Milli volt (mV). All the glass apparatus that were used are made of BOROSILICATE GLASS and were properly calibrated.

Potentiometric titration

Titration no 1: Standardization of 0.1 M NaOH solution was performed with potassium hydrogen phthalate (KHPhthalate) by using potentiometric method where ethanol was used as solvent.

Titration no 2: Assay of Aspirin solutions (Tablet) was performed by using Potentiometric method and the results were validated by using different parameters (linearity, accuracy and precision) statistically. The results were obtained by using 50, 100, 150, 200, 250, 300 mg of powdered tablet and the results were statistically validated.

Results and discussion

Potentiometric method

The method was followed by using formula from according to I.P. as:                               

1 ml 0.5 M of NaOH is equivalent to 0.04504 gm of Aspirin.

Actual strength found during the experiment was 0.15 M.

Linearity

The linearity of an analytical procedure is its ability (within a given range) to obtain test results, which are directly proportional to the concentration (amount) of analyte in the sample. In order to determine the quantity of any analyte present in unknown sample, some kind of relationship (mathematical/empirical) between concentration and response was essential where response should be directly proportional to the concentration (Tewari et. al., 2017).

Table 1. Linearity of Aspirin (Powdered Tablet)

50 mg

100 mg

150 mg

200 mg

250 mg

300 mg

Vol. of

NaOH(x)

mV(y)

Vol. of

NaOH(x)

mV(y)

Vol. of

NaOH(x)

mV(y)

Vol. of

NaOH(x)

mV(y)

Vol. of

NaOH(x)

mV(y)

Vol. of

NaOH(x)

mV(y)

0

260

0

192

0

232

0

251

0

268

0

273

5

110

5

53

5

104

5

100

5

114

5

112

10

73

10

9

10

29

10

53

10

63

10

93

15

-133

15

-127

15

-127

15

-132

15

-163

15

-144

20

-144

20

-140

20

-140

20

-140

20

-168

20

-156

25

-156

25

-168

25

-168

25

-155

25

-180

25

-160

30

-160

30

-169

30

-175

30

-160

30

-210

30

-170

Table 1. Continue….

Wt.(mg)

Wt. (gm)

x1(initial vol. of NaOH)

x2(final vol. of NaOH)

y1(mV of x1)

y2(mV of x2)

y(mV at end point)

x(end point) ml

Wt. (gm)

% assay

50

0.05

10

15

73

-133

0

11.772

0.1590612

158.12233

100

0.1

10

15

9

-127

0

10.331

0.1395909

109.59088

150

0.15

10

15

29

-127

0

10.929

0.1476792

98.452821

200

0.2

10

15

53

-132

0

11.432

0.154475

77.237514

250

0.25

10

15

63

-163

0

11.394

0.1539531

61.581239

300

0.3

10

15

93

-144

0

11.96202532

0.1616309

53.876962

Figure 1. Linearity graph of Aspirin

Within a range of 100-200 mg powdered tablet the process was linear.

Accuracy

The accuracy of an analytical procedure express closeness of agreement between the values, which is accepted either as a conventional true value or an accepted reference value and the value can be found.

Evaluation

At each concentration level % mean recovery, SD and % RSD were calculated.

Acceptance criteria

Assay recovery should be between 98%-102%. A simple logic behind this performance characteristic was whether the procedure was capable of estimating a true value or not (Tewari et. al., 2017).

Table 2. Accuracy of Aspirin (Powdered Tablet)

50 mg

100 mg

150 mg

200 mg

250 mg

300 mg

Vol. of

NaOH(x)

mV(y)

Vol. of

NaOH(x)

mV(y)

Vol. of

NaOH(x)

mV(y)

Vol. of

NaOH(x)

mV(y)

Vol. of

NaOH(x)

mV(y)

Vol. of

NaOH(x)

mV(y)

0

237

0

242

0

268

0

251

0

253

0

261

5

1

5

2

5

65

5

84

5

95

5

100

10

-100

10

-298

10

-245

10

-55

10

85

10

93

15

-147

15

-293

15

-261

15

-132

15

-255

15

-261

20

-144

20

-290

20

-267

20

-140

20

-261

20

-263

25

-156

25

-282

25

-271

25

-155

25

-268

25

-268

30

-160

30

-297

30

-272

30

-160

30

-275

30

-271

Table 3. % Recovery

Actual wt(mg)

x1(initial vol. of NaOH)

x2(final vol. of NaOH)

y1(mV of x1)

y2(mV of x2)

y(mV at end point)

x(end point) ml

Wt. got (mg)

% recovery

50

10

15

1

-297

0

10.01678

70.16168

140.3234

100

10

15

22

-298

0

10.34375

99.88636

99.88636

150

10

15

55

-245

0

10.91667

151.9697

101.3131

200

10

15

99

-255

0

11.39831

195.755

97.8775

250

10

15

80

-120

0

12

250.4545

100.1818

300

10

15

103

-100

0

12.53695

299.2678

99.75593

The result found to be accurate at 100-300 mg of powdered tablet.

Precision

Precision is the measurement of how close the data values to each other for a number of measurements under the same analytical conditions. Precision may be considered at three levels according to ICH.

System Precision

Precision under same operative conditions (within a laboratory over a short period of time using the same analyst with the same equipment) was determined. Mean, SD and %RSD were calculated from data. The system precision is checked by using standard chemical substance to ensure that the analytical system is working properly. In this retention time and area of six determinations is measured and % RSD should be calculated.

Method Precision

In method precision, a homogenous sample of single batch should be analysed 6 times. This indicates whether a method is giving consistent results for a single batch. In this analysis the sample has been analysed six times with the calculation of %RSD.

Intermediate Precision (Ruggedness)

Precision under different laboratory conditions (within-laboratory variation, as on different days, or with different analysts, or equipment within the same laboratory) has been carried out.

Reproducibility

Precision between laboratories/intermediate precision can be considered during the standardization of a procedure before it is submitted to the pharmacopoeia. A simple logic behind this parameter was some degree of inconsistency (occurrence of random error) was allowed for every analytical measurement. But, the extent depends on steps involved (weighing, dilution etc.), technique used in other expected variables (stability) and intended use of the procedure (Tewari et. al., 2017).

Table 4. Precision of Aspirin (Powdered Tablet)

250 mg..1

250 mg..2

250 mg…3

250 mg…4

250 mg…5

250 mg…6

Vol. of

NaOH(x)

mV(y)

Vol. of

NaOH(x)

mV(y)

Vol. of

NaOH(x)

mV(y)

Vol. of

NaOH(x)

mV(y)

Vol. of

NaOH(x)

mV(y)

Vol. of

NaOH(x)

mV(y)

0

205

0

245

0

183

0

232

0

248

0

202

5

100

5

122

5

120

5

122

5

126

5

112

10

73

10

90

10

83

10

99

10

105

10

114

15

-244

15

-256

15

-261

15

-238

15

-212

15

63

20

-276

20

-267

20

-270

20

-268

20

-266

20

-256

25

-278

25

-267

25

-279

25

-270

25

-279

25

-268

30

-276

30

-268

30

-268

30

-270

30

-266

30

-270

Figure 2. Determination of end point

Table 5. % Assay calculation

z

x1

x2

y1

y2

y

xml(end point)

Wt. (gm)

% assay

1

10

15

73

-244

0

11.151

0.2511

100.45199

2

10

15

90

-256

0

11.301

0.2545

101.79561

3

10

15

83

-261

0

11.206

0.2524

100.94721

4

10

15

99

-238

0

11.469

0.2583

103.31134

5

10

15

105

-212

0

11.656

0.2625

104.99861

6

15

20

63

-256

0

15.98746082

0.36

144.01505

-

Mean

S.D.

% RSD

11.357

0.206233099

1.815963346

-

-

Method was found to be precised up to 5 consecutive results. So it is evident that 300mg drug was precised according to the result.

Conductometric method

Actual strength found during the experiment was 0.25M

Table 6. Linearity of Aspirin (Powdered Tablet)

00mg:

 

200mg:

 

300mg:

 

400mg:

 

500mg:

 

Vol. of NaOH(x)

mV(y)

Vol. of NaOH(x)

mV(y)

Vol. of NaOH(x)

mV(y)

Vol. of NaOH(x)

mV(y)

Vol. of NaOH(x)

mV(y)

0

0.00097

0

0.00117

0

0.00103

0

0.00055

0

0.00173

5

0.148

5

0.052

5

0.0876

5

0.0421

5

0.0862

10

0.284

10

0.094

10

0.136

10

0.078

10

0.156

15

0.378

15

0.137

15

0.183

15

0.111

15

0.202

20

0.463

20

0.187

20

0.232

20

0.144

20

0.24

25

0.547

25

0.257

25

0.289

25

0.175

25

0.309

30

0.626

30

0.279

30

0.345

30

0.216

30

0.373

The linearity of an analytical procedure is its ability (within a given range) to obtain test results, which are directly proportional to the concentration (amount) of analyte in the sample. In order to determine the quantity of any analyte present in unknown sample, some kind of relationship (mathematical/empirical) between concentration and response was essential where response should be directly proportional to the concentration (Tewari et. al., 2017).

Table 7. % Recovery Calculation

Wt. (mg)

Xml (End Point)

Wt.  (gm)(x)

% Assay

100

5

0.1126

112.6

200

10

0.2252

112.6

300

10

0.2252

75.06667

400

15

0.3378

84.45

500

10

0.2252

45.04

Mean = 85.951333; SD = 28.349471; % RSD = 32.98317.

Figure 3. Linearity graph of Aspirin

So it is evident that within the range of 100-200 mg of drug, the method is Linear.

Accuracy

The accuracy of an analytical procedure express closeness of agreement between the values, which is accepted either as a conventional true value or an accepted reference value and the value can be found.

Evaluation

At each concentration level % mean recovery, SD and % RSD were calculated.

Acceptance criteria

Assay recovery should be between 98%-102%. A simple logic behind this performance characteristic was whether the procedure was capable of estimating a true value or not (Tewari et. al., 2017).

Table 8. Accuracy of Aspirin (Powdered Tablet)

100mg:

200mg:

300mg:

400mg:

500mg:

Vol. of NaOH

mV (y)

Vol. of NaOH

mV (y)

Vol. of NaOH

mV (y)

Vol. of NaOH

mV (y)

Vol. of NaOH

mV (y)

0

0.00089

0

0.00072

0

0.00094

0

0.00076

0

0.00207

5

0.134

5

0.0362

5

0.7528

5

0.00092

5

0.05602

10

0.260

10

0.0927

10

0.09098

10

0.133

10

0.8326

15

0.317

15

0.152

15

0.126

15

0.162

15

0.143

20

0.398

20

0.229

20

0.217

20

0.215

20

0.179

25

0.462

25

0.318

25

0.325

25

0.243

25

0.265

30

0.532

30

0.467

30

0.382

30

0.283

30

0.328

Table 9. % recovery Calculation

Actual wt (mg)

End Point (y)

Wt. got (mg)(x)

% Recovery

100

5

100

100

200

15

300

150

300

15

300

100

400

10

200

50

500

15

300

60

Hence the recovery of the aspirin came accurately at the values of 100 mg & 300 mg.

Precision was evaluated with by taking 300mg of powdered drug

Table 10. Precision of Aspirin (Powdered Tablet)

S. No.

End Point

Wt. (gm)

% Assay

1

21.12

0.105956

0.035319

2

21.05

0.159986

0.053329

3

20.75

0.109855

0.036618

4

20.47

0.850988

0.028366

5

21.2

0.13492

0.044973

6

21.38

0.360038

0.120013

Mean = 20.995; S.D = 0.330015151; % RSD = 1.571874976

So it is evident that 300mg drug was precised according to the result.

Conclusion

The developed method was completely validated showing satisfactory data for all method validated parameters tested.  It was seen that both these methods were linear at 100-200 mg of drug concentration. In case of potentiometry it showed accuracy in between 100-300 mg of drug concentration where in case of conductometric it is having 100 mg and 300 mg. In case of potentiometry results were precised if we take 250 mg and in case of conductometry the precised results were found in 300 mg of drug concentration. So it can be concluded that both this electrochemical method can be conveniently used having wide range of concentration for the assay of bulk drugs as well as for pharmaceutical dosage form in quality control laboratory as the proposed method can be used to analyse aspirin in its pharmaceuticals forms without interference from excipients since potentiometric method was seems to have more effective one rather than the conductometric method one.

Acknowledgement

The authors are thankful to the respected Principal Sir, Dr. Arnab Samanta, Netaji Subhas Chandra Bose Institute of Pharmacy, West Bengal for providing necessary facilities for the completion of research work.

Conflicts of interest: Nil

References

Bagchi A, Raha A, Mukherjee P, Chokroborty S, Hossain I. 2016. Development and validation of a comparative study of standardization process between titrimetric method and a method of electrochemistry (potentiometry). International Journal of Recent Advances in Pharmaceutical Research, 6(2):19-27.

Beckett AH, Stenlake JB. 2007. Practical Pharmaceutical Chemistry. 4th Ed., Vol. I & II. CBS Publishers and Distributors, New Delhi.

Tewari A, Bagchi A, Raha A, Mukherjee P, Pal M. 2017. Preparation, Estimation and Validation of the parameters of the standard curve of Ibuprofen by comparative study. Asian Journal of Pharmacy and Pharmacology, 3(3):79-85.

Watson DG. 2012. Pharmaceutical Analysis. 3rd Ed., Churchill Livingstone, London: Harcourt Publishers Limited, Essex CM 20 2JE.

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