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.
Limit: NMT 30 seconds
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:
Apparatus: Paddle
Medium: 0.1 M HCl; 500ml
Speed: 50rpm
Time: 10 minutes
Limit: NLT 85% of the stated amount of ondansetron
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 310nm. Calculate the content of Ondansetron in the medium from the absorbance obtained from a solution of known concentration of ondansetron hydrochloride 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 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 substances: Determine by liquid chromatography.
Test Solution: Weigh and powder 20 tablets. Disperse a quantity of the powder containing 40mg ondansetron with 100ml of the mobile phase. Centrifuge a portion of this solution at 3000rpm for 10 minutes. Use the supernatant.
Reference solution (a). A 0.0004 per cent w/v solution of 1,2,3,9-tetrahydro-9-methyl-3-methlene-4H-carbazol-4-one reference standard in acetonitrile.
Reference solution (b). A 0.004 per cent w/v solution of 2-methylimidazole in acetonitrile.
Reference solution (c). A 0.004 per cent w/v solution of ondansetron reference standard in acetonitrile.
Reference solution (d). Dilute 5ml of reference solution to 100 ml with the mobile phase.
Reference solution (e). Dilute 10.0ml of reference solution (d) to 100ml with the mobile phase.
Reference solution (f). Transfer 5.0ml of each reference solution (a), (b) and (c) to a 100ml volumetric flask, dilute to volume with the mobile phase.
Chromatographic system:
- A stainless steel column 25cm X 4.6 mm, packed with porous silica chemically bonded to nitrile groups(5µm),
- Mobile phase: a mixture of 20 volumes of acetonitrile and 80 volumes of buffer solution prepared by dissolving 2.7gm of monobasic potassium phosphate in 1000ml of water, adjusting to pH 5.4 with 1M sodium hydroxide,
- Flow rate: 1.5ml per minute,
- Spectrophotometer set at 216nm,
- Injection volume: 20µl
The relative retention time with reference to ondansetron for 2-methylimidazole is about 0.16 and for ondansetron impurity D is about 0.45.
Inject reference solution (e) & (f). The test is not valid unless the resolution between the ondansetron and adjacent peak is not less than 1.5, the theoretical plates is not less than 8000 for ondansetron and tailing factor is not more than 2. In the chromatogram obtained with reference solution(f). In the chromatogram obtained with reference solution (e), the signal to noise ratio for the ondansetron peak is not less than 15.
Inject reference solution (d) and the test solution. In the chromatogram obtained with the test solution the area of any secondary peak due to 2-methyl imidazole is not more than 0.15per cent, multiply with correction factor 1.89, the area of peak due to ondansetron impurity D is not more than 0.12 per cent, multiply with correction factor 0.77. The area of any other secondary peak is not more than 0.1 per cent and the sum of all the secondary peaks is not more than 0.5 per cent.
12.0) Uniformity of content: Determined by liquid chromatography, using the chromatographic conditions and the reference solution described in the assay.
Test solution: Disperse one tablet in the 0.01 M HCl and filter, dilute if necessary, to 100.0ml with 0.01 M HCl and filter.
Calcultae the content of ondansetron in the tablet.
13.0) Assay: Determined by liquid chromatography.
Reference solution (a). A 0.004 per cent w/v solution of ondansetron reference standard in 0.01 M hydrochloric acid.
Reference solution(b). A 0.014 per cent w/v solution of 3[Dimethylamino methyl]-1,2,3,9-tetrahdro-9-methyl-H-carbazol-4-one-RS (ondansetron impurity A reference standard) in 0.01 M HCl.
Reference solution(c). Transfer 8.0ml each of reference solution (a) and (b) to 50ml volumetric flask and dilute to volume with 0.01 M HCl.
Test solution: Weigh and powder 20 tablets. Disperse a quantity of powder containing about 40mg of ondansetron with about 60ml of 0.01 M hydrochloric with the aid of ultrasound for about 10 minutes and dilute 100.0ml. Filter through polypropylene membrane of 0.45 µm pore size. Discard first few ml of the filtrate. Dilute 1.0ml of the solution to 10.0ml with 0.01 M HCl.
Chromatographic system:
- A stainless steel column 25cm X4.6mm, packed with nitrile group bonded to porous silica (5µm)
- Mobile Phase: a mixture of 52 volumes of 0.272 per cent w/v solution of monobasic potassium phosphate, adjusted to pH 5.4 with 1M sodium hydroxide and 48 volumes of acetonitrile,
- Flow rate: 1.5ml per minute,
- Spectrophotometer set at 216nm,
- Injection volume: 10µl
The relative retention time with reference to ondansetron for ondansertron impurity A is about 1.1.
Inject reference solution (c). The test is not valid unless the resolution between the peaks due to ondansetron and ondansetron impurity A is not less than 1.5 and tailing factor is not more than 2.0 for ondansetron peak.
Inject reference solution(a) and the test solution.
Calculate the content of Ondansetron the tablet.
Alternative Method: By UV Spectrophotometer
Reference Solution: Weigh 30mg of reference standard of Ondansetron HCl in 50ml of volumetric flask. Add 10ml of 0.1 M HCl into it and sonicate to dissolve. Dilute 1ml of this solution to 50ml with same solvent.
Test Solution: Weigh and powder 20 tablets. Weight sample equivalent to 5mg of Ondansetron in 100ml volumetric flask add 10ml 1.0 M HCl into it and sonicate to dissolve the test sample. Make up to mark with 0.1M HCl. Filter and dilute5ml of this solution to 25ml in same solvent.
Check Absorbance of test as well as reference standard at 310nm in UV Spectrophotometer.
Calculate the content of Ondansetron.
Formula for calculation:
Absorbance of TEST STD wt. (mg) 1 100 25 Potency
—————————-X——————–X———X————–X———X———–X Avg. Wt.
Absorbance of STD 50 50 Test wt (mg) 5 100
Acceptance criteria: 90.0%-110.0%
