1.0) Description: Visual

2.0) 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%

4.0)      Identification Test:

In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak 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 0.01 M HCl

Time:  30 minutes

Speed: 50 rpm

Limit: NLT 65% for 10 minutes and NLT 85% of the stated amount of Fexofenadine HCl.

Withdraw a suitable volume of the medium and filter.

Determine by liquid chromatography.

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

Reference solution (a): Dissolve a weighed quantity of fexofenadine HCl reference standard in the dissolution medium to obtain a solution having a known concentration similar to that expected for the solution under test.

Note: A small amount of methanol, not exceeding 0.5 per cent of the total volume, can be used to dissolve fexofenadine HCl.

Reference solution (b): A 0.044 per cent w/v solution of benzene acetic acid,-4-[1-oxy-4(4-(hydroxydiphenyl-methyl)-1-piperidinyl]butyl)-α,α-dimethyl reference standard( fexofenadine impurity A reference standard) in water. To 1.0ml of this solution ass 40ml of reference solution (a).

Note: A small amount of acetic acid, not exceeding 5 per cent of the total volume, can be used to dissolve fexofenadine impurity A.

Chromatographic system:

• A stainless steel column 10cmX4.6 mm, packed with octadecylsilane bonded to porous silica (5µm)
• Mobile phase: a mixture of 30 volumes of a buffer solution prepared by dissolving 1.0g of monobasic sodium phosphate, 0.5 g of sodium perchlorate, and 0.3ml of O.P.A. in 300ml of water and 70 volumes of acetonitrile,
• Flow rate: 1ml per minute,
• Spectrophotometer set at 220nm,
• Injection volume: 20µl

Inject reference solution (b). The resolution between fexofenadine and fexofenadine impurity A is not less than 2.0.

Inject reference solution (a). The test is not valid unless the relative standard deviation for replicate injections is not more than 2.0 per cent.

Inject the reference solution and the test solution (a).

10.0)    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.

11.0)    Related substance: Determined by liquid chromatography.

Solvent mixture: 75 volumes of acetonitrile and 25 volumes of a 0.17 per cent v/v solution of glacial acetic acid

Test solution: Weigh and powder 20 tablets. Weigh a quantity of the powder containing 120mg of fexofenadine HCl, disperse in 20ml of 0.17 per cent v/v solution of glacial acetic acid, with vigorous shaking for 30 minutes and dilute to 100.0ml with acetonitrile, shake vigorously for 60 minutes, filter.

Reference solution (a): A solution containing 0.025 per cent w/v of fexofenadine HCl reference standard and 0.05 per cent w/v of fexofenadine impurity A reference standard in the solvent mixture. Dilute 3ml and 4.5ml, respectively, of the solutions to 50.0ml with the mobile phase.

Reference solution (b): A 0.025 per cent w/v solution of fexofenadine HCl reference standard in the solvent mixture. Dilute 4ml of the solution to 100.0ml with the mobile phase. Dilute 6ml of this solution to 100.0ml with the mobile phase.

Chromatographic system:

• A stainless steel column 25cmX4.6 mm, packed with phenyl groups chemically bonded to porous silica (5µm)
• Column temperature: 35°
• Mobile phase: a mixture of 64 volumes of a buffer solution prepared by diluting 7.5ml acetonitrile and 7.5ml of triethylamine to 1000ml with 0.17 per cent v/v glacial acetic acid in water, adjust the pH to 5.2 with O.P.A. and 36 volumes of acetonitrile
• Flow rate: 1.5ml per minute,
• Spectrophotometer set at 220nm,
• Injection volume: 20µl

Inject the reference solution (b). The test is not valid unless the relative standard deviation for replicate injections is not more than 6.0 per cent.

Inject reference solution (a). The relative retention time with respect to fexofenadine for fexofenadine impurity A is about 1.6. The resolution between fexofenadine and fexofenadine impurity A is not less than 7, the tailing factor is not more than2.0 and the relative standard deviation for replicate injections is not more than 2.0 per cent and not more than 3.0 per cent for fexofenadine and fexofenadine impurity A, repectively.

Inject the reference solution (a) and the test solution. In the chromatogram obtained with the test solution the area of the peak due to fexofenadine impurity A is not more than the area of the corresponding peak in the chromatogram obtained with reference solution (a) (0.4 per cent), the area of any individual impurity is not more than 0.2 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.25 per cent), the area of the peak due to decarboxilated degradanet[(+)-4-[1-hydroxy-4-[4-hydroxydiphenylmethyl)-1-piperidinyl]-bultyl]-isopropylbenzene having a relative retention time of 6.7 is not more than 0.12 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.15 per cent) and the sum of all the impurities is not more than 0.5 per cent. Ignore any peak with an area less than 0.04 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent).

12.0)    Assay: Determined by UV spectroscopy.

Solvent mixture: 75 volumes of acetonitrile and 25 volumes of a 0.17 per cent v/v solution of glacial acetic acid.

Test solution: Weigh and powder 20 tablets. Weigh a quantity of the powder containing 150mg of fexofenadine HCl, disperse in 20ml of a 0.17 per cent v/v solution of glacial acetic acid, with vigorous shaking for 30 minutes and dilute to 100.0ml with acetonitrile, shake vigorously for 60 minutes and filter. Dilute 1.0ml of this solution to 100.0ml with mobile phase.

Reference solution: A 0.025 per cent w/v solution of fexofenadine HCl reference standard in the solvent mixture. Dilute 3ml of the solution to 50.0ml with the mobile phase.

Chromatographic system:

• A stainless steel column 25cmX4.6 mm, packed with phenyl groups chemically bonded to porous silica (5µm)
• Column temperature: 35°
• Mobile phase: a mixture of 64 volumes of a buffer solution prepared by diluting 7.5ml acetonitrile and 7.5ml of triethylamine to 1000ml with 0.17 per cent v/v G.A.A. in water, adjust the pH to 5.2 with O.P.A. and 36 volumes of acetonitrile
• Flow rate: 1.5ml per minute,
• Spectrophotometer set at 220nm,
• Injection volume: 20µl

Inject the reference solution. The test is not valid unless the tailing factor is not more than 2.0 and the 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 Fexofenadine HCl in the tablets.

Formula for calculation:

Area of test        STD wt.      1             100                    3          Potency

—————- X————-X—-X——————X———X———-X Average weight

Area of STD        100          100      Weight of test       50          100

Acceptance criteria: 95.0%-105.0%

13.0)    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

HCl: Hydrochloride

O.P.A.: Orthophosphoric acid

G.A.A.: Glacial acetic acid

w/v: Weight/Volume