Telmisartan and Amlodipine Tablets USP – Specification & STP

The specification and Analytical Testing Procedure (ATP) / Standard Testing Procedure (STP) for the drug product Telmisartan and Amlodipine Tablets USP (as per USP monograph). The below procedures are most updated and revised.

Specification & STP of Telmisartan and Amlodipine Tablets USP

Specification of  Telmisartan and Amlodipine Tablets USP

Sr. No. Test Parameter Specification
1 Description As per Standard Formulation
2 Identification A. In the assay, retention time of Amlodipine and Telmisartan peak in the sample solution should be corresponding to the retention time of Amlodipine and Telmisartan peak obtained in standard solution.

B. In the assay, the UV spectra of Amlodipine and Telmisartan peak in the sample solution should be     corresponding to the UV spectra of Amlodipine and Telmisartan peak obtained in standard solution.
3 Average weight 

As per Standard Formulation
4 Uniformity of weight ± 5 % of average weight
5 Friability Not more than 1.00 % w/w
6 Uniformity of Dosage Units by Content Uniformity First Criteria :
The requirements for dosage uniformity are met if the acceptance value of the first 10 dosage units is less than or equal to L1 %. (L1 is 15.0 and L2 is 25.0.)Second Criteria :
If the acceptance value is > L1%, test the next 20 units, and calculate the acceptance value. The requirements are met if the final acceptance value of the 30 dosage units is ≤ L1%, and no individual content of any dosage unit is less than [1- (0.01) (L2)]M nor more than [1 + (0.01) (L2)] M. (L1 is 15.0 and L2 is 25.0.)
7 Dissolution of Telmisartan and Amlodipine Tablet USP Telmisartan :
Not less than 80.0% (Q) of labeled amount is released in 20 minutes
Amlodipine :
Not less than 80.0% (Q) of labeled amount is released in 20 minutes
8 Organic Impurities i.      Amlodipine related compound A : Not more than 1.0 %
ii.     Amlodipine Mannitol Adduct : Not more than 0.50 %
iii.    Any Individual impurity : Not more than 0.20 %
iv.     Total impurity (known and unknown) : Not more than 2.0 %
9 Assay of Telmisartan and Amlodipine Tablet USP Each tablet contains :
Telmisartan USP : 95.0 % to 105.0 % of labeled amount.
Amlodipine Besylate USP equivalent to Amlodipine : 90.0 % to 110.0 % of labeled amount

 

Analytical Method of  Telmisartan and Amlodipine Tablets USP

1.0     Description

2.0     Identification

    • Observe the chromatograms obtained under assay.
    • In assay, the retention time of the principal peaks due to Amlodipine and Telmisartan obtained with the sample solution corresponds to the retention time of the principal peaks due to Amlodipine and Telmisartan in the chromatogram obtained with standard solution.

3.0     Average weight

    • Carry out the weight on 20 tablets.

4.0     Uniformity of weight

    • Carry out the weight on 20 tablets.

5.0    Friability

    • Carry out the test as SOP.

6.0     Uniformity of Dosage Units (For Amlodipine): By HPLC

    • Procedure:  Carry out the test on 10 tablets as per assay procedure. Calculate the acceptance value As per USP General Chapter <905>:

  • Chromatographic Conditions:

    • As described under assay method.
    • Blank solution: As defined under assay.
    • Standard solution: As described under assay method.
  • Sample solution:
    • Transfer one tablet to a 50 ml amber coloured volumetric flask.
    • Add 10 ml acetonitrile and sonicate for 5 minutes to disperse.
    • Add 30 ml diluent and sonicate for further 15 minutes under cold conditions with intermittent shaking.
    • Make up the volume with diluent and mix.
    • Filter through 0.45 µm PVDF membrane filter.
    • Repeat the same procedure on 9 tablets again.
  • Procedure: 
    • Inject Blank solution.
    • Inject standard solution, five replicates, and measure the peak response for the peak due to Amlodipine, in terms of area.
    • System suitability: As defined under assay.
    • Inject test solution, single replicate, and measure the response for the peak due to Amlodipine in terms of area.

Calculate content of Amlodipine in each tablet, in percent, as per the following calculation.

At x Ws x 7 x 50 x 408.88 x P x 100

———————————————

As x 100 x 20 x 1 x 567.06 x 100 x C

    • Where,
    • At= Area of Amlodipine peak in test solution
    • As= Average area of Amlodipine peak in standard solution
    • Ws= Weight of Amlodipine Besylate working standard taken, in mg
    • P= Purity of Amlodipine working standard on as is basis
    • C= Label claim
    • 408.88 = Molecular weight of Amlodipine Base
    • 567.06 = Molecular weight of Amlodipine Besyalte

  • Uniformity of Dosage Unit: Telmisartan by content uniformity:

    • Procedure: 

  • Chromatographic Conditions:

    • As described under assay method.
    • Blank solution: As defined under assay.
    • Standard solution: As described under assay method.
    • Sample solution:
    • Transfer one tablet to a 50 ml amber coloured volumetric flask.
    • Add 10 ml acetonitrile and sonicate for 5 minutes to disperse.
    • Add 30 ml diluent and sonicate for further 15 minutes under cold conditions with intermittent shaking.
    • Make up the volume with diluent and mix.
    • Filter through 0.45 µm PVDF membrane filter.
    • Repeat the same procedure on 9 tablets again.
    • Transfer 5ml of filtered sample stock solution in to a 50ml clean and dry volumetric flask and make up to the volume with diluent, mix well.
    • Procedure: 
    • Inject Blank solution.
    • Inject standard solution, five replicates, and measure the peak response for the peak due to Amlodipine, in terms of area.
    • System suitability: As defined under assay.
    • Inject test solution, single injection from each preparation, and measure the response for the peak due to Telmisartan in terms of area.

Calculate content of Telmisartan in each tablet, in percent, as per the following calculation.

At x Ws x 4x 50 x 50 x P x 100

—————————————–

As x 100 x 20 x 1 x 5 x 100 x C

    • Where,
    • At= Area of Telmisartan peak in test solution
    • As= Average area of Telmisartan peak in standard solution
    • Ws= Weight of Telmisartan working standard taken, in mg
    • P= Purity of Telmisartan working standard on as is basis
    • C= Label claim

7.0     Dissolution of Telmisartan and Amlodipine Tablet USP:

  • Dissolution Conditions:
    • Dissolution medium: Dilute 3.4 ml of Hydrochloric acid to make 4000 ml (0.01 N HCl).
    • Medium Volume : 500 ml, 0.01 M Hydrochloric acid in amber colored jar
    • Apparatus: Paddle
    • Temperature: 37° ± 0.5 °C
    • RPM: 75
    • Time: 20 minutes
  • Chromatographic Conditions:
    • Column                                     : Inertsil ODS 3V, C18, 150 x 4.6 mm, 5 µm
    • Flow Rate                                 : 1.0 ml per minute.
    • Detection                                  : UV-257 nm
    • Injection Volume                    : 20 µl
    • Column Temp                         : 30° C
    • Auto Sampler temperature  : 10 °C
    • Run Time                                 : Not less than 1.5 times the retention time of Telmisartan.
  • Buffer preparation:
    • Dissolve 3.4322 g of Sodium Dihydrogen Phosphate and 2 ml of triethylamine in 1000 ml of water.
    • Adjust its pH to 6.0 ± 0.05 with dilute orthophosphoric acid and mix.
  • Mobile Phase:
    • Prepare a filtered and degassed mixture of 600 volumes of buffer and 400 volumes of acetonitrile.
  • Blank solution:
    • Use Dissolution medium, after filtration through 0.45 µm membrane filter, as blank solution.

  • Standard stock solution for Amlodipine Besylate:

    • Weigh and transfer accurately 35 mg of Amlodipine Besylate working standard in clean and dry 50 ml amber colored volumetric flask.
    • Add 30 ml dissolution medium and sonicate to dissolve.
    • Make up the volume with dissolution medium and mix.
  • Standard solution:
    • Dilute 2 ml of the Standard stock solution of Amlodipine Besylate to 100 ml with dissolution media and mix. Filter through 0.45 µm PVDF membrane filter.
  • Sample solution:
    • Place one tablet in each jar containing 500 ml dissolution media.
    • Run the dissolution apparatus for exactly 20 minutes.
    • At the end of prescribed time with draw a portion of the sample mid-way between jar and the shaft of the paddle and filter through 0.45 µm membrane filter.
  • Procedure:
    • Inject Dissolution medium as a blank solution.
    • Inject standard solution, five replicates, and measure the peak response, in terms of area, for Amlodipine. Calculate the system suitability as under.
    • Tailing factor: Not more than 2.5
    • Area % RSD: Not more than 2.0
    • Inject test solution, single injection, from each preparation.
    • Measure the peak response, in terms of area for the major peak due to Amlodipine.

Calculate the drug released (Amlodipine), with respect to claim, in each tablet as per the following calculation

At x Ws x 2 x 500 x 408.88 x P x100

———————————————–

As x 50 x 100 x 1 x 567.06 x 100 x C

    • Where,
    • At= Area of Amlodipine peak in test solution
    • As= Average area of Amlodipine peak in standard solution
    • Ws= Weight of Amlodipine Besylate working standard taken, in mg
    • P= Purity of Amlodipine working standard on as is basis
    • C= Label Claim
    • 408.88 = Molecular weight of Amlodipine Base
    • Molecular weight of Amlodipine Besylate

  • Dissolution Conditions For Telmisartan:

    • Medium: 900 ml, phosphate buffer pH 7.5 in amber coloured jar
    • Phosphate Buffer pH 7.5 preparation:
      • Dissolve 6.8045 g of Potassium Dihydrogen Phosphate and 1.596 g of Sodium hydroxide in 1000 ml of water. Adjust its pH to 7.5 ± 0.05 with dilute sodium hydroxide or phosphoric acid, if necessary.
    • Apparatus: Paddle
    • Temperature: 37° ± 0.5 °C
    • RPM: 75
    • Time: 20 minutes

  • Chromatographic Conditions: As under dissolution of Amlodipine

    • Solvent mixture:
    • Add 5 ml of triethylamine in 500 ml of water and further add 500 ml of Acetonitrile and mix.
    • Blank solution:
    • Use Dissolution medium as blank solution.
    • Standard stock solution for Telmisartan:
    • Weigh and transfer accurately 45.0 mg of Telmisartan working standard in clean and dry 50 ml amber coloured volumetric flask. Dissolve in and make up the volume with solvent mixture.
    • Standard solution:
    • Dilute 5 ml of the Standard stock solution of Telmisartan to 100 ml with dissolution media. Filter through 0.45 µm membrane filter.
    • Sample solution:
    • Place one tablet in each jar containing 900 ml dissolution media.
    • Run the dissolution apparatus for exactly 20 minutes.
    • At the end of prescribed time with draw a portion of the sample mid-way between jar and the shaft of the paddle and filter through 0.45 µm membrane filter.

  • Procedure:

    • Inject Dissolution medium as blank solution.
    • Inject standard solution, five replicates, and measure the peak response, in terms of area, for Telmisartan. Calculate the system suitability as under.
    • Area % RSD: Not more than 2.0
    • Tailing factor: Not more than 2.0
    • Inject test solution, single injection, from each preparation.
    • Measure the peak response, in terms of area for the major peak due to Telmisartan.

Calculate the drug released (Telmisartan), with respect to claim, in each tablet as per the following calculation

At x Ws x 5 x 900 x P x100

————————————–

As x 50 x 100 x 1 x 100 x LC

    • Where,
    • At= Area of Telmisartan peak in test solution
    • As= Average area of Telmisartan peak in standard solution
    • Ws= Weight of Telmisartan working standard taken, in mg
    • P= Purity of Telmisartan working standard on as is basis
    • LC= Label Claim

8.0     Organic Impurities Test for Telmisartan and Amlodipine Tablet USP:

  • Chromatographic Condition:
    • Column              :  Inertsil ODS-3V, C18, 250 x 4.6 mm, 5 µm
    • Flow Rate              :  1.0 ml per minute.
    • Wave Length       :  UV-257 nm
    • Injection Volume : 20 µl
    • Autosampler Temperature: 10° C
    • Column Temp     : Ambient at constant temperature
  • Buffer preparation:
    • Weigh accurately and dissolve 1.77 g of Ammonium acetate into 900 ml of water.
    • Adjust pH to 5.5 ± 0.05 with Orthophosphoric acid. Make up the volume to 1000 ml.
  • Mobile phase A:
    • Prepare filtered and degassed mixture of 80 volumes of buffer and 20 volumes of acetonitrile.

  • Mobile phase B:

    • Prepare filtered and degassed mixture of 35 volumes of buffer and 65volumes of acetonitrile.
  • Diluent:
    • Weigh accurately and dissolve 1.77 g of Ammonium acetate into 900 ml of water.
    • Adjust its pH to 2.0 ± 0.05 with Orthophosphoric acid.
    • Make up the volume to 1000 ml.
    • Prepare filtered and degassed mixture of 60 volumes of buffer and 40 volumes of acetonitrile.
  • Test solution:
    • Weigh and transfer accurately quantity of tablet powder equivalent to 25 mg of Amlodipine to 100 ml volumetric flask.
    • Add 70 ml of solvent mixture and sonicate to dissolve the contents for 15 minutes.
    • Make up the volume with the same solvent and mix. Filter through 0.45 µm membrane filter.

  • Stock standard solution for Telmisartan:

    • Weigh and transfer accurately 25 mg of Telmisartan working standard to 50 ml volumetric flask.
    • Add 30 ml diluent and sonicate to dissolve the contents.
    • Make up the volume with the same solvent and mix.

  • Stock standard solution for Amlodipine:

    • Weigh and transfer accurately 34 mg of Amlodipine Besylate working standard to 200 ml volumetric flask.
    • Add 150 ml of diluent and sonicate to dissolve the contents.
    • Make up the volume with the same solvent and mix.
  • Standard solution:
    • Transfer 10 ml of stock standard solution for Telmisartan and 5 ml of stock standard solution for Amlodipine to 200 ml volumetric flask.
    • Dilute to volume with diluent and mix.
    • Filter through 0.45 µm PVDF membrane filter.

  • Sensitivity solution:

    • Transfer 5 ml of stock standard solution for Telmisartan and 7 ml of stock standard solution for Amlodipine to 200 ml volumetric flask.
    • Dilute to volume with diluent and mix.
    • Dilute 2 ml of the resulting solution to 100 ml with diluent and mix.
    • Filter through 0.45 µm PVDF membrane filter.
  • Gradient program: 
Time (in minutes) Mobile Phase A (% v/v) Mobile Phase B(% v/v)
0 95 5
5 95 5
15 70 30
35 45 55
50 5 95
65 0 100
70 0 100
75 95 5
80 95 5

  • Procedure:

    • Inject sensitivity solution and measure the peak response for the peaks due to Amlodipine and Telmisartan. Calculate the system suitability as under.
    • Signal to Noise ratio: Should be greater than10
    • Inject standard solution. Measure the peak response for the peaks due to Amlodipine and Telmisartan. Calculate the system suitability as under.
    • Tailing factor for Telmisartan and Amlodipine peak is not be more than 2.5 in standard solution.
    • The relative standard deviation for replicate injections is not more than 5.0 in standard solution.
    • Inject test solution and measure the peak response for the major peaks in terms of area.
  •  Peak table:
Sr. No. Peak Name Relative Retention Time Relative Response Factor (F) Acceptance Criteria, NMT (%)
 1. Besylate 0.08 —– —–
 2. Amlodipine Related Compound A 0.59 0.39 1.0
 3. Amlodipine Mannitol Adduct 0.67 1.00 0.50
 4. Amlodipine 0.74 —– —–
 5. Telmisartan Related Compound A* 0.78 —– —–
 6. Telmisartan Related Compound B* 0.86 —– —–
 7. Telmisartan 1.0 —– —–
 8. Any Individual Impurity —– —– 0.2
 9. Total Impurities —– —– 2.0

*Process impurities controlled in the drug substance. (Note: Disregard any peak less than 0.1 %.)

Calculate the impurities in percent as per the following calculation.

  • Amlodipine Related Compound A

At x Ws x 5 x 100 x P x 1 x 408.88 x Av

————————————————-

As x 200 x 200 x Wt x LC x F x 567.05

    • Where
    • At: Peak area of Amlodipine related compound A in test solution
    • As: Average peak area of Amlodipine from standard solution chromatograms
    • Ws:  Weight of Amlodipine Besylate working standard (in mg)
    • P: % Potency of Amlodipine Besylate working standard on as is basis
    • LC: Label claim of Amlodipine (mg/tablet)
    • Wt: Weight of sample taken (in mg)
    • Av: Average weight of tablet (in mg)
    • F: Relative response factor (See peak table)
    • 567.05: Molecular weight of Amlodipine Besylate
    • 408.88: Molecular weight of Amlodipine

  • Amlodipine Mannitol adduct

At x Ws x 5 x 100 x P x 1 x 408.88 x Av

————————————————-

As x 200 x 200 x Wt x LC x F x 567.05

    • Where
    • At: Peak area of Amlodipine Mannitol adduct in test solution
    • As: Average peak area of Amlodipine from standard solution chromatograms
    • Ws:  Weight of Amlodipine Besylate working standard (in mg)
    • P: % Potency of Amlodipine Besylate working standard on as is basis
    • LC: Label claim of Amlodipine (mg/tablet)
    • Wt: Weight of sample taken (in mg)
    • Av: Average weight of tablet (in mg)
    • F: Relative response factor (See peak table)
    • 567.05: Molecular weight of Amlodipine Besylate
    • 408.88: Molecular weight of Amlodipine

Calculate Individual Impurity for Amlodipine as per the following calculation.

At x Ws x 5 x 100 x P x 408.88 x Av

——————————————–

As x 200 x 200 x Wt x LC x 567.05

    • Where,
    • At: Peak area of individual impurity in test solution
    • As: Average peak area of Amlodipine from standard solution chromatograms
    • Ws:  Weight of Amlodipine Besylate working standard (in mg)
    • P: % Potency of Amlodipine Besylate working standard on as is basis
    • LC: Label claim of Amlodipine (mg/tablet)
    • Wt: Weight of sample taken (in mg)
    • Av: Average weight of tablet (in mg)
    • F: Relative response factor (See peak table)
    • 567.05: Molecular weight of Amlodipine Besylate
    • 408.88: Molecular weight of Amlodipine

Calculate Individual Impurity for Telmisartan as per the following calculation.

At x Ws x 10 x 100 x P x Av

———————————

As x 50 x 200 x Wt x LC

    • Where,
    • At: Peak area of individual impurity in test solution
    • As: Average peak area of Telmisartan from standard solution chromatograms
    • Ws:  Weight of Telmisartan working standard (in mg)
    • P: % Potency of Telmisartan working standard on as is basis
    • LC: Label claim of Telmisartan (mg/tablet)
    • Wt: Weight of sample taken (in mg)
    • Av: Average weight of tablet (in mg)
    • Combine Amlodipine impurities and Telmisartan impurities and report Amlodipine Related Compound A, Amlodipine Mannitol Adduct, Any Individual (Single Maximum) Impurity and Total Impurities.
    • Any Individual (Single Maximum) Impurity = Unknown Impurity from Telmisartan or Amlodipine, whichever is higher.
    • Total Impurities = Amlodipine Known and Unknown Impurities + Telmisartan Unknown Impurities.

9.0     Assay Test of Telmisartan and Amlodipine Tablet USP:

  • Chromatographic Condition:
    • Column                  : Inertsil, ODS-3V, C18, 250 x 4.6 mm, 5 µm
    • Flow Rate               : 1.0 ml per minute.
    • Detection                : UV-257 nm
    • Injection Volume     : 20 µl
    • Sampler temperature: 10° C
    • Column Temp         : 30° C
    • Run Time: Not less than 1.5 times the retention time of Telmisartan

  • Buffer preparation:

    • Dissolve 3.432 g of Sodium dihydrogen orthophosphate dihydrate in 900 ml of water.
    • Add 2 ml Triethylamine and mix. Adjust its pH to 6.0 ± 0.05 with orthophosphoric acid and mix.
    • Make up the volume to 1000 ml and mix.
  • Mobile Phase:
    • Prepare a filtered and degassed mixture of 600 volumes of buffer and 400 volumes of acetonitrile.
  • Diluent:
    • Add 5 ml of Triethylamine to 500 ml water and mix.
    • Prepare filtered and degassed mixture of 50 volumes of this solution and 50 volumes of acetonitrile.
  • Blank Solution:
    • Use diluent as blank solution.

  • Standard stock solution for Amlodipine Besylate:

    • Weigh and transfer accurately 40 mg of Amlodipine Besylate working standard to 100 ml amber coloured volumetric flask.
    • Dissolve in and make up the volume with diluent.

  • Standard stock solution for Telmisartan:

    • Weigh and transfer accurately 40 mg of Telmisartan working standard to 100 ml amber coloured volumetric flask.
    • Dissolve in and make up the volume with diluent.
  • Standard solution:
    • Transfer 4 ml of the Standard stock solution of Telmisartan and 7 ml of the Standard stock solution of Amlodipine Besylate to 20 ml volumetric flask.
    • Dilute to volume with diluent and mix.
    • Filter through 0.45 µm PVDF membrane filter.

  • Sample Solution:

    • Transfer 10 tablets, randomly selected, to 500 ml volumetric flask.
    • Add 100 ml acetonitrile and sonicate for 5 minutes to disperse.
    • Add 300 ml of diluent and sonicate for further 15 minutes under cold conditions with intermittent shaking.
    • Make up the volume with diluent and mix.
  • Sample solution for Amlodipine:
    • Filter sample solution through 0.45 µm PVDF membrane filter and use as such.

  • Sample solution for Telmisartan:

    • Dilute 5 ml of the sample solution to 50 ml with diluent and mix. Filter through 0.45 µm PVDF membrane filter.

  • Procedure: 

    • Inject Blank solution as a blank.
    • Inject standard solution, five replicates, and measure the peak response for the peaks due to Amlodipine and Telmisartan.
    • The order of elution is Amlodipine and Telmisartan.
    • Calculate the system suitability as per the following.
    • Theoretical plates: Not less than 2000 for each component
    • Tailing factor: Not more than 2.0 for Telmisartan and Not More Than 2.5 for Amlodipine
    • Area % RSD: Not more than 2.0 for each component
    • Inject sample solution, in duplicate, and measure the response for the major peaks due to Amlodipine and Telmisartan.

Calculate the content of Amlodipine, in mg, as per the following calculation.

At x Ws x 7 x 500 x 408.88 x P

——————————————

As x 100 x 20 x 10 x 567.06 x 100

    • Where,
    • At= Average area of Amlodipine peak in test solution
    • As= Average area of Amlodipine peak in standard solution
    • Ws= Weight of Amlodipine Besylate working standard taken, in mg
    • P= Purity of Amlodipine working standard on as is basis
    • 408.88 = Molecular weight of Amlodipine Base
    • 567.06 = Molecular weight of Amlodipine Besylate

Calculate the assay in percent, as per the following calculation

Assay (mg)

—————————————–x 100

Label claim

Calculate the content of Telmisartan, in mg, as per the following calculation.

At x Ws x 4 x 500 x 50 x P

——————————-

As x 100 x 20 x 10 x 5 x 100

    • Where,
    • At= Average area of Telmisartan peak in test solution
    • As= Average area of Telmisartan peak in standard solution
    • Ws= Weight of Telmisartan working standard taken, in mg
    • P= Purity of Telmisartan working standard on as is basis

Calculate the assay in percent, as per the following calculation

Assay (mg)

——————————— X 100

Label claim

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