STP FOR TELMISARTAN TABLETS

• Description: Visual
• Average Weight: Check weight of 20 tablets at randomly and calculate the average weight by formula :  wt of 20 tablets (gm) x 1000 / 20. found avg. wt in mg

3.0)                  Uniformity of weight:

Weigh 20 tablets selected at random and calculate the average weight. Not more than two of the individual weights deviate from the average weight by more than the percentage shown in table.

Tablets were weighed individually and the percentage of deviation of its weight from the average weight was determined for each tablet. Formula for calculate the percentage of deviation = (experimental weight – theoretical weight)    x 100%

Theoretical weight

 Average weight of tablets Percentage deviation More than 80mg but Less than 250mg 7.5% 250mg or More 5%
• Identification Test:

Extract a quantity of the powdered tablets containing 10mg of Methotrexate with sufficient 0.1 M sodium hydroxide to produce 100ml, filter and dilute 1ml of the filtrate to 100ml with 0.1 M sodium hydroxide.

When examined in the range 230nm to 380nm, the resulting solution shows absorption maxima at about 258nm, 303nm and 371nm.

5.0)      Hardness:

The standard method used for tablet hardness testing is compression testing. The tablet is placed between two jaws that crush the tablet. The machine measures the force applied to the tablet and detects when it fractures. Although compressive force is applied to the tablet, along the diameter of the tablet at right angles to the applied force.

6.0)      Disintegration Time

Unless otherwise stated in the individual monograph, introduce one tablet into each tube and add a disc to each tube. The assembly is suspended in the liquid medium in a suitable vessel, preferably a 1-litre beaker. The volume of liquid is such that the wire mesh at its highest point is at least 15mm below the surface of the liquid, and at its lower point is at least 25mm above the bottom of the beaker. At no time should the top of the basket-rack assembly become submerged. There is a thermostatic arrangement for heating the liquid and maintaining the temperature at 37±2°.

If 1 or 2 tablets fail to disintegrate, repeat the test on 12 additional tablets; not less than 16 of the total of 18 tablets tested disintegrate.

If the tablets adhere to the disc and the preparation under examination fails to comply, repeat the test omitting the disc. The preparation complies with the test if all the tablets in the repeat test disintegrate.

7.0)      Dimension of Tablet:

Length, breadth and thickness are determined by vernier in mm

8.0)      Dissolution:

Apparatus: Paddle

Medium: 900ml of phosphate buffer pH 7.5 prepared by dissolving 13.61gm of potassium phosphate in about 800ml of water, adjusted to pH 7.5 with 2M sodium hydroxide, and diluted with water to 1000ml,

Time: 30 minutes

Speed: 75 rpm

Limit: NLT 80% of the stated amount of Telmisartan.

Withdraw a suitable volume of the medium and filter. Reject the first few ml of filtrate and dilute a suitable volume of the filtrate with dissolution medium. Measure the absorbance of the resulting solution at the maximum at about 296nm. Calculate the content of temlisartan in the medium from the absorbance obtained from a solution prepared by dissolving 44mg of telmisartan reference standard in 1ml of 0.1 M sodium hydroxide, and dilute to 100ml with methanol. Further dilute this solution with dissolution medium to obtain a solution with final concentration of 0.001 per cent telmisartan.

9.0)      Leak test:

The apparatus is used to test for the integrity of packed strips, blisters and Alu-Alu Blister pack containing tablets. Ensure apparatus bath is filled with purified water upto mark indicated and add 0.5% crystal violet solution in water. Samples are placed into the desiccators and the lid is placed in position. The pump starts to produce a vacuum 15inHg inside the desiccators and the vacuum is held for 1 minute. The sample remains at the required vacuum level for given time interval buzzer will sound after time is over and will cut off the vacuum pump. As the package is immersed in a colored dye solution the venting of the desiccators will allow any holes to be penetrated by the dye and the contents of the flexible packaging will also be stained with the same coloring material.

Examine all the strips for any leakage by opening the pockets manually. If anyone pocket shows evidence of leakage, reject the sample, stop the Blister / Strip machine and immediately take corrective action.

10.0)    Related substance: Determined by liquid chromatography.

Solvent mixture: 80 volumes of buffer solution prepared by diluting 5.0ml of triethylamine to 2000ml with water and 20 volumes of methanol.

Test solution: Weigh and powder 20 tablets. Disperse a quantity of powder containing 100mg of telmisartan in 100.0ml of solvent mixture with the aid of ultrasound of 45 minutes and filter.

Reference solution: A 0.0005 per cent w/v solution of telmisartan reference standard in the solvent mixture.

Chromatographic system:

• A stainless steel column 15cmX4.6 mm, packed with octadecylsilane bonded to porous silica (5µm)( such as Inertsil ODS-3)
• Mobile phase: A. Dissolve 0.5 gm of potassium dihydrogen phosphate in 1000ml of water; add 2ml of triethylamine, adjusted to pH 3.2 with O.P.A.
1. Acetonitrile
• A gradient programme using the conditions given below, flow rate: 1.8ml per minute,
• Spectrophotometer set at 298nm,
• Injection volume: 20µl

Inject the reference solution and the test is not valid unless the theoretical plates is not less than 3000, tailing factor is not more than 2.0 and relative standard deviation for replicate injections is not more than 5.0 percent.

Inject the reference solution and the test solution, In the chromatography obtained with the test solution the area of any secondary peak is not more than the area of the principal peak in the chromatogram obtained with the reference solution (0.5 per cent), the sum of the areas of all the secondary peak is not more than 4times the areas of the principal peak in the chromatogram obtained with reference solution (2.0 per cent). Ignore any peak with an area less than 0.1 times the area of the principal peak in the chromatogram obtained with the reference solution (0.05 per cent).

 Time (in min.) Mobile phase A (Percent v/v) Mobile phase B (percent v/v) 0 78 22 6 80 20 7 70 30 15 60 40 25 60 40 26 40 60 35 20 80 40 78 22

11.0)    Assay: Determined by liquid chromatography.

Solvent mixture: 80 volumes of buffer solution prepared by diluting 5.0 ml of triethylamine to 2000ml with water and 20 volumes of methanol.

Test solution: Weigh and powder 20 tablets. Disperse a quantity of powder containing 40mg of telmisartan in 100ml of the solvent mixture and sonicate for 45 minutes. Dilute 5.0ml of this solution to 50.0ml with the solvent mixture.

Reference solution: A 0.004 per cent w/v solution of telmisartan reference standard in the solvent mixture.

Chromatographic system:

• A stainless steel column 15cmX4.6 mm, packed with octadecylsilane bonded to porous silica (5µm) ( such as Inertsil ODS-3)
• Mobile phase: a mixture of 60 volumes of buffer solution prepared by dissolving .72gm of potassium dihydrogen phosphate in 1000ml of water; add 2ml of triethylamine and adjust the pH to 2.4 with O.P.A. and 40 volumes of acetonitrile.
• Flow rate: 1ml per minute,
• Spectrophotometer set at 298nm,
• Injection volume: 20µl

Inject reference solution. The test is not valid unless the theoretical plates is not less than 3000, the tailing factor is not more than 2.0 and relative standard deviation for replicate injections is not more than 2.0 per cent. Inject the reference solution and the test solution.

Calculate the content of telmisartan in the tablets.

Formula for calculation:

Area of test        STD wt.         5          100                  50      Potency

—————-–X————-X——-X—————-X——-X———-XAverage weight

Area of STD       100              50     Weight of test      5        100

Alternative Method: By UV Spectrophotometer

Test Solution: Weigh and powder 20 tablets. Weight sample equivalent to 40mg of Telmisartan in 100ml volumetric flask add some 0.1 M NaOH into it and sonicate to dissolve the test sample. Make up to mark with 0.1M NaOH.  Filter and dilute 1ml of this solution to 50ml in same solvent.

Reference Solution: Weigh 40mg of reference standard of telmisartan in 100ml of volumetric flask. Add 20ml of 0.1 M NaOH into it and sonicate to dissolve. Dilute 1ml of this solution to 50ml with same solvent.

Check Absorbance of test as well as reference standard at 296nm in UV Spectrophotometer.

Calculate the content of Telmisartan.

Formula for calculation:

Absorbance of TEST       STD wt. (mg)        1            100                50        Potency

—————————-X——————–X———X————–X———X———–X Avg. Wt.

Absorbance of STD            100                    50       Test wt (mg)      1            100

Acceptance criteria: 90.0%-110.0%

12.0)    MICROBIOLOGICAL PURITY

Perform the test according to requirements of IP,

Total aerobic Microbial count (TAMC): NMT 103 CFU/g

Total combined yeasts/Moulds count (TYMC): NMT 102 CFU/g

Pathogens: in 1gm drug.

Escherichia Coli – Should be absent

Pseudomonas aeroginosa – Should be absent

Salmonella – Should be absent

Staphylococcus aureus– Should be absent

Abbreviations:

Wt.: Weight

mg: Miligram

ml: Milileter

STD: Standard

inHg: Inch of Mercury

rpm: Rounds per minute

CFU: Colony forming unit

NaOH: Sodium hydroxide

OPA: Orthophosphoric acid