1.0 Description: White color, round shaped, uncoated tablet having one side mid break line and other side plain.
2.0 Average Weight: Check weight of 20 tablets at randomly and calculate the average weight by formula.
Average weight (mg) = wt of 20 tablets (gm) x 1000
20
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.
Deviation (%) = Weight of each tablet – Average weight x 100
Average weight
| Average weight of tablets | Percentage deviation |
| More than 80 mg but Less than 250 mg | 7.5% |
| 250 mg 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 15 mm below the surface of the liquid, and at its lower point is at least 25 mm 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:
Diameter and thickness are determined by vernier calliper 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 6.5 g. For tablets with a unit weight of more than 650 mg, 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.
% Friability = W1 – W2 X 100
W1
W1= Initial weight W2= Final weight
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.
If obviously cracked, chipped or broken tablets are present in the sample after tumbling, the sample fails the test.
9.0) Dissolution:
Apparatus: Paddle
Medium: 900 ml of 0.1 M hydrochloric acid.
Speed: 50 rpm
Time: 45 minutes
Withdraw a suitable volume of the medium and filter. Dilute the filtrate, if necessary with the dissolution medium. Measure the absorbance of the resulting solution at the maximum at about 280 nm. Calculate the content of Amisulpride in the medium from the absorbance obtained from a solution of known concentration of Amisulpride reference standard, prepared by dissolving in minimum quantity of methanol and diluted with the dissolution medium to get similar concentration of the test solution.
Formula:
Absorbance of test
———————— X STD Dilution X Test Dilution X Potency of STD X 100
Absorbance of STD
Limit: N.L.T. 75% of the labeled amount of Amisulpride is dissolved.
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:
Determined by liquid chromatography.
Solvent mixture: 30 volumes of water and 70 volumes of methanol.
Test solution: Weigh and powder 20 tablets. Disperse a quantity of powder containing 1gm of amisulpride with 40 ml of water. Add about 125 ml of methanol and sonicate for 30 minutes with intermittent shaking and dilute to 250.0 ml with solvent mixture and allow settling for 10 minutes. Dilute the solution with the solvent mixture to obtain a concentration of 0.1 per cent w/v of amisulpride, filter.
Reference solution: A 0.001 per cent w/v solution of amisulpride reference standard in the solvent mixture.
Chromatographic system:
- A stainless steel column 25 cm X 4.6 mm, packed with octylsilane bonded to porous silica (5µm),
- Mobile Phase: 0.07 per cent w/v solution of 1-octane sulphonic acid sodium in 0.25 per cent v/v of sulphuric acid,
- methanol,
- A gradient programme using the condition given in table:
- Flow rate: 1.5 ml per minute,
- Spectrophotometer set at 225 nm,
- Injection volume: 10 µl
| Time
(in min.) |
Mobile phase
(per cent w/v) |
Mobile phase
(per cent v/v) |
| 0 | 70 | 30 |
| 18 | 64 | 36 |
| 35 | 48 | 52 |
| 45 | 48 | 52 |
| 46 | 70 | 30 |
| 56 | 70 | 30 |
Inject the reference solution. The test is not valid unless the column efficiency is not less than 5000 theoretical plates and the tailing factor is not more than 2.0.
Inject the reference solution and the test solution. In the chromatogram obtained with the test solution, the area of any secondary peak is not more than the 0.3 times the area of the principal peak in the chromatogram obtained with the reference solution (0.3 per cent) and the sum of areas of all the secondary peaks is not more than the area of the principal peak in the chromatogram obtained with the reference solution (1.0 per cent).
12.0) Assay:
Determined by liquid chromatography.
Solvent mixture: 30 volumes of water and 70 volumes of methanol.
Test solution: Weigh and powder 20 tablets. Disperse a quantity of powder containing 1000 mg of Amisulpride with 40 ml of water. Add about 125 ml of methanol and sonicate for 30 minutes with intermittent shaking and dilute to 250.0 ml with the solvent mixture and allow settling for 10 minutes. Dilute with solvent mixture to obtain a solution having a known concentration similar to reference solution.
Reference solution: A 0.01 per cent w/v solution of amisulpride reference standard in the solvent mixture.
Chromatographic system:
- A stainless steel column 15 cm X 4.6 mm, packed with octysilane bonded to porous silica (5µm),
- Mobile Phase: A. a mixture of 90 volumes of buffer solution containing 0.07 per cent w/v solution of 1-octane sulphonic acid sodium in 0.25 per cent v/v of diluted sulphuric acid and 10 volumes of methanol.
B Mixture of 10 volumes of buffer solution and 90 volumes of methanol.
- A gradient programmed using the conditions given below;
- Flow rate: 1.0 ml per minute,
- Spectrophotometer set at 280 nm,
- Injection volume: 10 µl
| Time
(in min) |
Mobile phase A
(per cent w/v) |
Mobile phase
( per cent v/v) |
| 0 | 70 | 30 |
| 6 | 70 | 30 |
| 10 | 55 | 45 |
| 15 | 70 | 30 |
| 20 | 70 | 30 |
Inject the reference solution. The test is not valid unless the column efficiency is not less than 3000 theoretical plates and 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 reference solution and the test solution.
Calculate the content of Amisulpride in the tablet.
Formula:
Area of Test STD Wt. (mg) 5 250 Potency
—————–X—————–X——–X—————X———–X Average weight
Area of STD 100 50 Test Wt. (mg) 100
Alternative Method: By UV Spectrophotometer
Test Solution: Weigh and powder 20 tablets. Weight sample equivalent to 50 mg of Amisulpride in 100 ml volumetric flask add l0 ml 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 1 ml of this solution to 50ml in same solvent.
Reference Solution: Weigh 50 mg of reference standard of Amisulpride in 100 ml of volumetric flask. Add 10 ml 0.1 M HCl into it and sonicate to dissolve. Make up to mark with 0.1 M HCl. Dilute 1 ml of this solution to 50ml with same solvent.
Check Absorbance of test as well as reference standard at 239 nm in UV Spectrophotometer.
Calculate the content of Amisulpride.
Formula for calculation:
Absorbance of TEST STD wt. (mg) 1 100 50 Potency
—————————-X——————–X———X————–X———X———–X Avg. Wt.
Absorbance 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: Milligram
ml: Milliliter
STD: Standard
inHg: Inch of Mercury
rpm: Rotations per minute
CFU: Colony forming unit
w/v: Weight/volume
