- 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% |
- Identification Test:
- Transfer a quantity of the finely powdered tablets containing 250mg of levetiracetam to a 50ml volumetric flask, add 35ml of the acetone, sonicate for 15 minutes and dilute to 50ml with acetone, filter 10ml solution through a membrane filter and evaporate the filtrate to dryness for crystallization, scratching the sides of the vessel, on the residue, determine by infrared absorption sepectrophotometry. Compare the spectrum with that obtained with 0.1 per cent w/v solution of levetiracetam reference standard in acetone, treated in the same manner, beginning with 10ml solution.
- 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:
Apparatus: Paddle
Medium: 900ml of water
Speed: 50 rpm
Time: 30 minutes
Limit: NLT 85% of the labeled amount of Levetiracetam is dissolved.
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: A solution containing 0.04 per cent w/v of Levetiracetam reference standard in the solvent mixture and sonicate. Dilute further, if necessary.
Chromatographic system:
- A stainless steel column 25cm X4.6mm, packed with octadecylsilane bonded to porous silica (4µm).
- Mobile phase: a mixture of 92 volumes of a buffer solution prepared by dissolving 1.4g of monobasic potassium phosphate and 0.6 g of sodium 1-haptanesulphonate in 1000ml of water and adjusted to pH 2.8 with orthophosphoric acid and 8 volumes of acetonitrile,
- Flow rate: 2ml per minute.
- Spectrophotometer set at 220nm,
- Injection volume: about 10µl
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: Weigh and powder 20 tablets. Disperse a quantity of the powder containing 120mg of levetiracetam in the mobile phase, diluting to 100ml with mobile phase and filter.
Note: Sonicate if necessary, and centrifuge the solution before passing through a suitable filter.
Reference solution (a): A solution containing 0.00036 per cent w/v each of Levetiracetam reference standard and Levetiracetam impurity B reference standard in mobile phase.
Reference solution (b): A solution containing 0.00036 per cent w/v of Levetiracetam reference standard in the mobile phase.
Chromatographic system:
- A stainless steel column 25cm X4.6mm, packed with octadecylsilane bonded to porous silica (4µm).
- Mobile phase: a mixture of 95 volumes of a buffer solution prepared by dissolving 6.8g of monobasic potassium phosphate and 0.85 g of sodium 1-haptanesulphonate in 1000ml of water and adjusted to pH 2.8 with orthophosphoric acid and 5 volumes of acetonitrile,
- Flow rate: 1ml per minute.
- Spectrophotometer set at 200nm,
- Injection volume: about 10µl
| Name | Relative retention time | Correction factor |
| Levetiracetam impurity B1 | 0.54 | – |
| Levetiracetam | 1.0 | – |
| Levetiracetam impurity A1,2 | 1.7 | – |
| Levetiracetam acid3 | 2.1 | 1.27 |
Inject reference solution (a) and (b). The test is not valid unless the resolution between levetiracetam impurity B and levetiracetam is not less than 2.0 obtained with reference solution (a), the tailing factor for levetiracetam peak is not more than 2.0 and the relative standard deviation for replicate injections is not more than 10.0 per cent obtained with reference solution (b).
Inject reference solution (b) and the test solution. In the chromatogram obtained with the test solution, the area of any peak corresponding to levetiracetam acid is not more than area of the principal peak in the chromatogram obtained with reference solution (b) (0.3 per cent). The area of any other secondary peak is not more than 0.33 the area of the principal peak in the chromatogram obtained with reference solution (b) (0.1 per cent). The sum of areas of all the secondary peaks is not more than 2 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.6 per cent).
11.0) Assay: Determined by liquid chromatography.
Solvent mixture: 20 volumes of acetonitrile and 80 volumes of water.
Test solution: Weigh and powder 20 tablets. Transfer a quantity of the powder containing about 40mg of Levetiracetam in 100ml volumetric flask and add aboutb 80ml of solvent mixture and disperse with aid the aid of ultrasound for about 10 minutes, cool and dilute to volume with solvent mixture and filter.
Reference solution: A solution containing 0.04 per cent w/v of levetiracetam reference standard in the solvent mixture.
Chromatographic system:
- A stainless steel column 25cm X4.6mm, packed with octadecylsilane bonded to porous silica (4µm).
- Mobile phase: a mixture of 92 volumes of a buffer solution prepared by dissolving 1.4g of monobasic potassium phosphate and 0.6 g of sodium 1-haptanesulphonate in 1000ml of water and adjusted to pH 2.8 with orthophosphoric acid and 8 volumes of acetonitrile,
- Flow rate: 2ml per minute.
- Spectrophotometer set at 220nm,
- Injection volume: about 10µl
Inject 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 test solution.
Calculate the content of Levetiracetam in the tablets.
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:
mg: Miligram
ml: Milileter
inHg: Inch of Mercury
rpm: Rounds per minute
CFU: Colony forming unit
