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)      Friability:

The test is applicable to compressed tablets and is intended to determine the physical strength of tablets. For tablets with an average weight of 0.65 gm or less take a sample of whole tablets corresponding to about 6.5gm and for tablets with an average weight of more than 0.65gm take a sample of 10 tablets.

Dedust the tablets carefully and weigh accurately the required number of tablets. Place the tablets in the drum and rotate it 100 times (25 rpm for 4 minutes). Remove the tablets, remove any loose dust from them and weigh them accurately. The test is run only once unless the results are difficult to interpret or if the weight loss is greater than the target value, in which case, the test is repeated twice and the mean of the three tests is determined.

Formula: initial wt. – after friability wt. x100 / initial wt.

A maximum loss of weight (From a single test or from the mean of three tests) not greater than 1.0 percent is acceptable for most tablets.

9.0)      Dissolution:

Medium: 900ml of 0.1 M Hydrochloric acid

Time: 45 minutes

Speed: 50 rpm

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

Withdraw a suitable volume of the medium and filter.

Determine by liquid chromatography.

Test solution: Use the filtrate.

Reference solution: Dissolve a quantity of olpatadine HCl reference standard in the dissolution medium to obtain a solution of concentration similar to the expected concentration of the test solution.

Chromatographic system:

• A stainless steel column 25cmX4.6 mm, packed with octadecylsilane bonded to porous silica (5µm)
• Mobile phase: a mixture of 72 volumes of a buffer solution prepared by dissolving 6.8gm of potassium dihydrogen orthophosphate in 1000ml of water, adjusted to pH 4.5 with O.P.A. or triethylamine and 28 volumes of acetonitrile.
• Flow rate: 1ml per minute,
• Spectrophotometer set at 210nm,
• Injection volume: 20µl

Inject the reference solution and the test solution.

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.

Test solution: Disperse a quantity of the powder containing 25mg of Olpatadine HCl with 60ml of mobile phase, ultrasound for 10 minutes, and dilute to 100.0ml with the mobile phase. Centrifuge at about 2500 rpm for 10 minutes, and dilute 5.0ml of this solution to 25.0ml with the mobile phase.

Reference solution: Dissolve a quantity of olpatadine HCl reference standard in the dissolution medium to obtain a solution of concentration similar to the expected concentration of the test solution.

Chromatographic system:

• A stainless steel column 25cmX4.6 mm, packed with octadecylsilane bonded to porous silica (5µm)
• Mobile phase: a mixture of 72 volumes of a buffer solution prepared by dissolving 6.8gm of potassium dihydrogen orthophosphate in 1000ml of water, adjusted to pH 4.5 with O.P.A. or triethylamine and 28 volumes of acetonitrile.
• Flow rate: 1ml per minute,
• Spectrophotometer set at 210nm,
• Injection volume: 20µl

Inject the test solution. The area of any secondary peak is not more than 1.0 per cent and the sum of area of all the secondary peaks is not more than 2.0 per cent, calculated by area normalization.

12.0)    Assay: Determined by liquid chromatography.

Test solution: Weigh and powder 20 tablets. Disperse a quantity of the powder containing 25mg od olpatadine HCl with 60ml of mobile phase, ultrasound for 10 minutes, and dilute to 100.0ml with the mobile phase. Centrifuge at about 2500rpm for 10 minutes and dilute 5ml of this solution to 25ml with mobile phase.

Reference solution: Dissolve 25mg of olpatadine HCl reference standard in 15ml of mobile phase and dilute to 50.0ml with mobile phase. Dilute 5.0ml of this solution to 50.0ml with the mobile phase.

Chromatographic system:

• A stainless steel column 25cmX4.6 mm, packed with octadecylsilane bonded to porous silica (5µm)
• Mobile phase: a mixture of 72 volumes of a buffer solution prepared by dissolving 6.8gm of potassium dihydrogen orthophosphate in 1000ml of water, adjusted to pH 4.5 with O.P.A. or triethylamine and 28 volumes of acetonitrile.
• Flow rate: 1ml per minute,
• Spectrophotometer set at 210nm,
• Injection volume: 20µl

Inject the reference solution. The test is not valid unless the column efficiency is not less than 4000 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 per cent.

Inject the reference solution and test solution.

Calculate the content of Olpatadine HCl in tablet.

Formula for calculation:

Area of Test        STD wt.           5                100                 25           Potency

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

Area of STD        50                  25     Weight of test       5                   100

Acceptance criteria: 90.0%-110.0%

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

NaOH: Sodium hydroxide

O.P.A.: Orthophosphoric acid

HCl: Hydrochloric acid