## STP FOR EBASTINE 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.

Weigh the tablets individually and calculate the percentage of deviation for each tablet. By using formula =(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%

4.0)      Identification Test:

In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to that in the chromatogram obtained with the reference solution.

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:

Medium: 900ml of 0.5 per cent w/v solution of sodium lauryl sulphate in 0.1 M HCl.

Speed: 100 rpm

Time: 45 minutes

Limit: NLT 75% of the stated amount of Ebastine.

Withdraw a suitable volume of the medium and filter.

Determine by liquid chromatography.

Test solution: Dilute the filtrate, if necessary, with the dissolution medium.

Reference solution: Dissolve a quantity of ebastine reference standard in acetonitrile and dilute with the dissolution medium to obtain a solution having a concentration similar to that of the test solution.

Chromatographic system:

• A stainless steel column 25cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µ),
• Mobile Phase:a mixture of 25 volumes of 10.01 M potassium dihydrogen phosphate containing 1ml of triethylamine and 75 volumes of acetonitrile, adjusted to pH 7.0 with O.P.A.
• Flow rate: 1.5ml per minute,
• Spectrophotometer set at 255nm,
• Injection volume: 20µl
• Column temperature: 40°

Calculate the content of Ebastine in medium.

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 up to 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 substances: Determined by liquid chromatography.

Test solution: Disperse a quantity of powdered tablets containing 0.05g of Ebastine in 35ml of the solvent mixture with the aid of ultrasound and dilute to 50ml with the moble phase A. Centrifuge and filter.

Reference solution (a): Dilute 0.5ml of the test solution to a 100ml with the mobile phase.

Reference solution (b): A solution containing 0.002 per cent w/v each of ebastine impurity C reference standard and ebastine inmpurity D reference standard in the solvent mixture. Dilute 2.5ml of this solution to 25ml with mobile phase A.

Chromatographic system:

• A stainless steel column 25cm X4.6mm, packed with octylsilane bonded to porous silica (5µ),
• Mobile Phase A: 40 volumes of buffer solution prepared by dissolving 11.9g of O.P.A in 25ml water and dilute to 50ml with water. Dilute 25ml of this solution to 450ml with water, add 6ml diethylamine and dilute to 500ml with water, adjusted to pH 6.0 with diethylamine and 60 volumes of acetonitrile.
1. methanol,
• Flow rate: 1ml per minute,
• A gradient programme using the conditions given below,
• Spectrophotometer set at 210nm,
• Injection volume: 20µl

Inject reference solution (a) and (b). The test is not valid unless the resolution between the peaks due to ebastine impurity C and ebastine impurity D is not less than 1.5 in the chromatogram obtained with reference solution (b) and in the chromatogram obtained with solution (a), the tailing factor is not more than 2.0.

 Time ( in min.) Mobile phase A (per cent v/v) Mobile phase B (per cent v/v) 0 80 20 40 95 5 55 95 5 57 80 20 65 80 20

 Name Relative retention time Ebastine ImpurityC1 0.16 Ebastine ImpurityD2 0.17 Ebastine ImpurityA3 0.24 Ebastine ImpurityB4 0.42 Ebastine ImpurityF5 0.5 Ebastine ImpurityG6 0.7 Ebastine ( retention time about 28 minutes) 1.0 Ebastine ImpurityE7 1.35

Inject reference solution (a) and the test solution. In the chromatogram obtained with test solution, the area of any secondary peak is not more than 0.4 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.2 per cent) and the sum of the areas of all the secondary peaks is not more than 4 times the area of the principal peak in the chromatogram obtained with reference solution (a) (2.0 per cent).

11.0)    Uniformity of content:

(For tablets containing 10mg or less)

Solvent mixture: 25 volumes of a solution prepared by dissolving 0.3 g of O.P.A. in water and dilute to 500ml with water, adjusted to pH 5.0 with 1M sodium hydroxide, filter and 75 volumes of acetonitrile.

Test solution: Disperse 1 tablet in 1ml of water with intermittent shaking, add 20ml of the solvent mixture and sonicate for 5 minutes and dilute to 50ml with the solvent mixture, filter.

Reference solution: Dissolve a suitable quantity of ebastine reference standard in the solvent mixture and dilute with solvent mixture in such a manner to get similar concentration to that of test solution.

Chromatographic system:

• A stainless steel column 25cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µ),
• Mobile Phase: a mixture of 25 volumes of 0.01 M potassium dihydrogen phosphate containing 1ml of triethylamine and 75 ml of acetonitrile, adjusted to pH 7.0 with O.P.A.
• Flow rate: 1.5ml per minute,
• Spectrophotometer set at 255nm,
• Injection volume: 20µl

Calculate the content of Ebastine in the tablets.

12.0)    Assay: Determined by liquid chromatography.

Solvent mixture: 25 volumes of a solution prepared by dissolving 0.3 g of O.P.A. in water and dilute to 500ml with water, adjusted to pH 5.0 with 1M sodium hydroxide, filter and 75 volumes of acetonitrile.

Test solution: Weigh and powder 20 tablets. Disperse a quantity of the powder containing 0.05g of ebastine in 150ml of the solvent mixture with the aid of ultrasound for 5 minutes and dilute to 250ml with the solvent mixture and filter.

Reference solution: A 0.02 percent w/v solution of ebastine reference standard in solvent mixture.

Chromatographic system:

• A stainless steel column 25cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µ),
• Mobile Phase: a mixture of 25 volumes of 0.01 M potassium dihydrogen phosphate containing 1ml of triethylamine and 75 ml of acetonitrile, adjusted to pH 7.0 with O.P.A.
• Flow rate: 1.5ml per minute,
• Spectrophotometer set at 255nm,
• Injection volume: 20µl

Inject reference solution. The test is not valid unless the column efficiency is not less than 2500 theoretical plates, the tailing factor is not more than 2.0 and the relative standard deviation for replicate injections is not more than 2.0 percent.

Inject reference solution and the test solution.

Calculate the content of Ebastine in the tablet.

Alternative Method: By UV Spectrophotometer

Test Solution: Weigh and powder 20 tablets. Weight sample equivalent to 25mg of Ebastine 100ml volumetric flask add 20ml methanol into it and sonicate to dissolve the test sample. Make up to mark with methanol. Filter and dilute 2ml of this solution to 50ml in 0.1 M HCl.

Reference Solution: Weigh 25mg of reference standard of Ebastine in 50ml of volumetric flask. Add 20ml methanol into it and sonicate to dissolve. Make up to mark with methanol. Dilute 1ml of this solution to 50ml with 0.1 M HCl.

Check Absorbance of test as well as reference standard at about 257nm in UV Spectrophotometer.

Calculate the content of Ebastine in the tablets.

Formula:

Abs. of Test      STD Wt.(mg)  1            100              50      Potency

—————–X————–X——-X—————X——–X———–X Average wt.

Abs. of STD        50               50     Test Wt.(mg)      2          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

Abs. Absorbance

w/v: Weight/Volume

HCl: Hydrochloric acid

O.P.A.: orthophosphoric acid