STP FOR LEVAMISOLE TABLETS

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.

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%
• Identification Test:

In the test for related substances, the principal spot in the chromatogram obtained with test solution (b) corresponds to that in the chromatogram obtained with reference solution (a).

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. Tablets with a unit weight equal to or less than 650 mg, take a sample of whole tablets corresponding as near as possible to 6.5g. For tablets with a unit weight of more than 650mg, take a sample of 10 whole tablets. The tablets should be carefully dedusted prior to testing. Accurately weigh the tablet sample, and place the tablets in the drum. Rotate the drum 100 times and remove the tablets. Remove any loose dust from the tablets as before, and accurately weigh.

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 0.01 N HCl

Speed: 50 rpm

Time:  45 minutes

Limit: NLT 85% of the labeled amount of Levamisol is dissolved.

Withdraw a suitable volume of the medium and filter. Measure the absorbance of the filtered solution, suitably diluted with the medium if necessary, at the maximum at about 214nm. Calculate the content of levamisol in the medium from the absorbance obtained by repeating the determination using a solution of levamisol reference standard in the same medium.

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 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.

11.0)    Related substances:

Determined by thin-layer chromatography.

Mobile phase: A mixture of 60 volumes of toluene, 40 volumes of acetone and 1 volume of strong ammonia solution.

Test solution (a): Shake a quantity of the powdered tablets containing 100mg of levamisol with 5ml of methanol for 2 minutes and filter.

Test solution (b): Dilute 1ml of the test solution (a) to 10ml with methanol.

Reference solution (a): A 0.24 per cent w/v solution of Levamisol HCl reference standard in methanol.

Reference solution (b): Dilute 1ml of reference solution (a) to 20ml with methanol.

Apply to the plate 10µl opf each solution. After development, dry the plate at 105° for 15 minutes and examine under ultraviolet light at 254nm as well as after exposure to iodine vapour. Any secondary spot the chromatogram obtained with test solution (a) is not more intense than the spot in the chromatogram obtained with reference solution (b).

12.0)    Assay:

Weigh and powder 20 tablets. Weigh a quantity of the powder containing about 300mg of levamisol, add 30ml of water and shake for 10 minutes. Filter, wash the filter with 20ml of water and add the washings to the filtrate. To the combined filtrate add dilute ammonia solution to make it alkaline and extract with three quantities each of 25ml, 15ml and 15ml, of chloroform, filter through cotton wool covered with a layer of anhydrous sodium sulphate. Combine the chloroform extracts and evaporate to dryness. Dissolve the residue in 50ml of anhydrous glacial acetic acid. Titrate with 0.1 M perchloric acid, using crystal violet solution as indicator. Carry out blank titration.

1ml of 0.1 M perchloric acid is equivalent to 0.02043 g of Levamisol.

Alternative Method: By UV Spectrophotometer

Test Solution: Weigh and powder 20 tablets. Weight sample equivalent to 25mg of Levamisole 100ml volumetric flask add 20ml 0.1 M HCl into it and sonicate to dissolve the test sample. Make up to mark with 0.1 M HCl. Filter and dilute 1ml of this solution to 50ml in 0.1 M HCl.

Reference Solution: Weigh 25mg of reference standard of Levamisole HCl in 100ml of volumetric flask. Add 20ml 0.1 M HCl into it and sonicate to dissolve. Make up to mark with 0.1 M HCl. Dilute 1ml of this solution to 50ml with 0.1 M HCl.

Check Absorbance of test as well as reference standard at about 215nm in UV Spectrophotometer.

Calculate the content of Levamisole 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        100               50       Test Wt.(mg)        1         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

Abs. Absorbance

HCl: hydrochloric acid