- 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.
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 peaks in the chromatogram obtained with the test solution correspond to the peaks 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: 100 rpm
Time: 60 minutes
Limit: NLT 75% of the labeled amount of Escitalopram and Clonazepam is dissolved.
Withdraw a suitable volume of the medium and filter, rejecting first few ml of the filtrate.
Determine by liquid chromatography.
Test solution: The filtrate obtained as given above, diluted if necessary with the dissolution medium.
Reference solution: Dissolve an accurately weighed quantity of escitalopram oxalate reference standard and clonazepam reference standard in the dissolution medium and dilute with the dissolution medium to obtain a solution having a known concentration similar to the expected concentration of the test solution.
Chromatographic system:
- A stainless steel column 25cm X4.6mm, packed with octylsilane chemically bonded to porous silica (5µm),
- Mobile Phase: a mixture of 550 volumes of a buffer solution prepared by dissolving 6.8 g of potassium dihydrogen orthophosphate and 8.7g of dipotassium hydrogen orthophosphate in 1000ml of water, add 3ml of triethylamine and adjusted to pH 6 with O.P.A., 315 volumes of methanol, and 135 volumes of acetonitrile,
- Flow rate: 1.2ml per minute,
- Spectrophotometer set at 210nm,
- Injection volume: 100µl
Inject the reference solution and test solution.
Calculate the contents of escitalopram and clonazepam .
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 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.
10.0) Related substances:
Solvent mixture: 400 volumes of water, 300 volumes of methanol and 300 volumes of acetonitrile.
Test solution: Weigh and powder 20 tablets. Shake a quantity of the powder containing about 40mg of Escitalopram with 50ml of solvent mixture, ultrasound for 20 minutes, add sufficient solvent mixture to produce 100ml mix and filter.
Reference solution (a): Dissolve 10mg of clonazepam reference standard in 50ml of solvent mixture, ultrasound to dissolve and add sufficient solvent mixture to produce 100ml.
Reference solution (b): Dissolve 25.7mg of escitalopram oxalate reference standard in 40ml of solvent mixture, add 5.0ml reference solution (a) ultrasound and add sufficient solvent mixture to produce 50ml.
Chromatographic system:
- A stainless steel column 25cm X4.6mm, packed with octylsilane chemically bonded to porous silica (5µm),
- Mobile Phase: a mixture of 550 volumes of a buffer solution prepared by dissolving 6.8 g of potassium dihydrogen orthophosphate and 8.7g of dipotassium hydrogen orthophosphate in 1000ml of water, add 3ml of triethylamine and adjusted to pH 6 with O.P.A., 315 volumes of methanol, and 135 volumes of acetonitrile,
- Flow rate: 1.2ml per minute,
- Spectrophotometer set at 254nm,
- 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 secondary peaks is not more than 2.0 per cent, Calculate by area normalisation.
11.0) Uniformity of content:
(For tablets containing 10mg or less)
Determined by liquid chromatography,
Solvent mixture: 400 volumes of water, 300 volumes of methanol and 300 volumes of acetonitrile.
Test solution: Disperse one tablet with 20ml of solvent mixture for 30 minutes, add sufficient solvent mixture to produce 25ml, mix and filter.
Reference solution (a): Dissolve 10mg of clonazepam reference standard in 50ml of solvent mixture, ultrasound to dissolve and add sufficient solvent mixture to produce 100ml.
Reference solution (b): Dissolve 25.7mg of escitalopram oxalate reference standard in 40ml of solvent mixture, add 5.0ml reference solution (a) ultrasound and add sufficient solvent mixture to produce 50ml.
Chromatographic system:
- A stainless steel column 25cm X4.6mm, packed with octylsilane chemically bonded to porous silica (5µm),
- Mobile Phase: a mixture of 550 volumes of a buffer solution prepared by dissolving 6.8 g of potassium dihydrogen orthophosphate and 8.7g of dipotassium hydrogen orthophosphate in 1000ml of water, add 3ml of triethylamine and adjusted to pH 6 with O.P.A., 315 volumes of methanol, and 135 volumes of acetonitrile,
- Flow rate: 1.2ml per minute
- Spectrophotometer set at 254nm,
- Injection volume: 20µl
Inject the reference solution (b) and test solution.
Calculate the contents of Escitalopram and Clonazepam.
12.0) Assay: Determined by liquid chromatography.
Solvent mixture: 400 volumes of water, 300 volumes of methanol and 300 volumes of acetonitrile.
Test solution: Weigh and powder 20 tablets. Shake a quantity of the powder containing about 40mg of Escitalopram with 50ml of solvent mixture, ultrasound for 20 minutes, add sufficient solvent mixture to produce 100ml mix and filter.
Reference solution (a): Dissolve 10mg of clonazepam reference standard in 50ml of solvent mixture, ultrasound to dissolve and add sufficient solvent mixture to produce 100ml.
Reference solution (b): Dissolve 25.7mg of escitalopram oxalate reference standard in 40ml of solvent mixture, add 5.0ml reference solution (a) ultrasound and add sufficient solvent mixture to produce 50ml.
Chromatographic system:
- A stainless steel column 25cm X4.6mm, packed with octylsilane chemically bonded to porous silica (5µm),
- Mobile Phase: a mixture of 550 volumes of a buffer solution prepared by dissolving 6.8 g of potassium dihydrogen orthophosphate and 8.7g of dipotassium hydrogen orthophosphate in 1000ml of water, add 3ml of triethylamine and adjusted to pH 6 with O.P.A., 315 volumes of methanol, and 135 volumes of acetonitrile,
- Flow rate: 1.2ml per minute,
- Spectrophotometer set at 254nm,
- Injection volume: 20µl
The retention time of peaks due to escitalopram is about 10 minutes and clonazepam is about 14 minutes.
Inject reference solution (b). The test is not valid unless the relative standard deviation for replicate injections is not more than 2.0 per cent, and tailing factor is not more than 2.5, the column efficiency is not less than 5000 theoretical plates for escitalopram peak.
Inject the reference solution (b) and test solution.
Calculate the contents of Escitalopram and Clonazepam in the tablets.
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
O.P.A.: Orthophosphoric acid
w/v: Weight/volume
