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% |
4.0) Identification:
- Powder an appropriate number of tablets to prepare about 0.055 per cent w/v solution of risperidone in ethyl acetate, shake for 30 minutes and centrifuge for 20 minutes. Evaporate 5ml of the supernatant liquid with the aid of a stream of nitrogen to dryness; the residue complies with the following test.
Determine by infrared absorption spectrophotometry. Compare the spectrum with that obtained with risperidone reference standard or with the reference spectrum of risperidone.
- 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: 500 ml of 0.1M HCl.
Speed: 50 rpm
Time: 45 minutes.
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: Dissolve a quantity of risperidone reference standard in the dissolution medium and dilute with the same solvent to obtain a solution having a known concentration similar to the test solution.
Chromatography system:
- A stainless steel column 15 cm x 4.6 mm packed with octadecylsilane bonded to porous
silica (5µm),
- Mobile phase; a mixture of 65 volumes of water, 35 volumes of acetonitrile and 0.1 volume of trifluoroacetic acid, adjust the pH to 3.0 with ammonia solution,
- flow rate: 1.5 ml per minute,
- Spectrophotometer set at 237 nm,
- Injection volume: 50 µl.
Inject the reference solution. The test is not valid unless the relative standard deviation of replicate injections is not more than 2.0 per cent.
Inject the reference solution and the test solution.
Calculate the content of Risperidone in the medium.
Limit: NLT 80 per cent of the stated amount of risperidone.
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,
Dilute sodium hydroxide solution: To 1000ml of water in a beaker, add 0.1M Sodium hydroxide dropwise to obtain a pH of about 8.5.
Dilute hydrogen peroxide solution: Dilute 1ml of hydrogen peroxide solution (10 volumes) with water to 500ml.
Solvent mixture: 80 volumes of methanol and 20 volumes of water.
Test solution: Transfer not less than 10 tablets to a suitable volumetric flask to obtain a 0.01 per cent w/v solution of risperidone. Add an appropriate amount of water equivalent to 20 per cent of the total volume of the volumetric flask, and shake mechanically for about 30 minutes. Add a volume of methanol equivalent to 60 per cent of the total volume of the volumetric flask, and shake mechanically for about 30 minutes, dilute with methanol to volume and filter.
Reference solution: Dissolve 10mg of risperidone reference standard in 10ml of dilute sodium hydroxide solution in a 100ml volumetric flask. Store the flask at 90° for 24 hours. Cool the solution to room temperature. Add 10ml of dilute hydrogen peroxide solution to the flask, and store at 90° for additional two hours. Cool the mixture to room temperature, and dilute with methanol to volume.
Chromatographic system:
- A stainless steel column 15 cm x 4.6 mm packed with octadecylsilane bonded to porous
silica (5µm),
- Mobile phase A; a mixture of 80 volumes of water, 19.5volumes of acetonitrile and 0.1 volume of trifluoroacetic acid, adjust the pH to 3.0 with ammonium hydroxide,
- a mixture of 61 volumes of water, 39 volumes of methanol and 0.1 volumes of trifluoroacetic acid, adjust the pH to 3.0 with ammonium hydroxide,
- flow rate: 2.5 ml per minute,
- Spectrophotometer set at 275 nm,
- Injection volume: 20 µl.
| Time
(in min.) |
Mobile phase A
( per cent v/v) |
Mobile phase B
( per cent v/v) |
| 0 | 100 | 0 |
| 8 | 100 | 0 |
| 16 | 0 | 100 |
| 20 | 0 | 100 |
| 21 | 100 | 0 |
| 25 | 100 | 0 |
| Name | Relative retention time | Correction factor |
| Bicyclorisperidone1 | 0.68 | 1.23 |
| Risperidone | 1.0 | – |
| Risperidone trans-N-oxide2 | 1.65 | – |
| Risperidone cis-N-oxide3 | 1.81 | 1.05 |
| Individual unidentified impurities | – | – |
| Total impurities | – | – |
Inject the reference solution. The test is not valid unless the resolution between the peaks due to risperidone trans-N-oxide and risperidone cis-N-oxide is not less than 1.2.
Inject the test solution. The area of any peak correspomding to bicyclorisperidone, and risperidone cis-N-oxide is not more than 0.5 per cent, the area of any other secondary peak is not more than 0.3 per cent and the sum of areas of all the secondary peaks is not more than 1.0 per cent, calculated by area normalization.
11.0) Uniformity of content:
Determined by liquid chromatography,
Test solution: Transfer 1 tablet to a 100ml volumetric flask. Add 50ml of 0.1 M HCl and shake mechanically for 30 minutes, dilute to the volume with 0.1 M HCl, filter.
Reference solution: Weigh accurately and dissolve the risperidone reference standard in 0.1 M HCl to obtain a solution having a known concentration similar to the test solution.
Chromatography system:
- A stainless steel column 15 cm x 4.6 mm packed with octadecylsilane bonded to porous
silica (5µm),
- Mobile phase; a mixture of 65 volumes of water, 35 volumes of acetonitrile and 0.1 volume of trifluoroacetic acid, adjust the pH to 3.0 with ammonia solution,
- flow rate: 1.5 ml per minute,
- Spectrophotometer set at 237 nm,
- Injection volume: 20 µl.
Inject the reference solution and the test solution.
Calculate the content of risperidpone in the tablet.
12.0) Assay:
Determine by liquid chromatography.
Solvent mixture: 80 volumes of methanol and 20 volumes of water.
Test solution: Transfer not less than 10 tablets to a suitable volumetric flask to obtain a 0.01 per cent w/v solution of risperidone. Add an appropriate amount of water equivalent to 20 per cent of the total volume of the volumetric flask, and shake mechanically for about 30 minutes. Add a volume of methanol equivalent to 60 per cent of the total volume of the volumetric flask, and shake mechanically for about 30 minutes, dilute with methanol to volume and filter.
Reference solution: A 0.01 per cent w/v solution of risperidone reference standard in the
solvent mixture.
Chromatographic system:
- A stainless steel column 15 cm x 4.6 mm packed with octadecylsilane bonded to porous
silica (5µm),
- Mobile phase A; a mixture of 80 volumes of water, 19.5volumes of acetonitrile and 0.1 volume of trifluoroacetic acid, adjust the pH to 3.0 with ammonium hydroxide,
- a mixture of 61 volumes of water, 39 volumes of methanol and 0.1 volumes of trifluoroacetic acid, adjust the pH to 3.0 with ammonium hydroxide,
- flow rate: 2.5 ml per minute,
- Spectrophotometer set at 275 nm,
- Injection volume: 20 µl.
Inject the reference solution. The test is not valid unless the tailing factor is not more than 2.5 and the relative standard deviation for replicate injections is not more than 2.0 per cent.
Inject the reference solution and the test solution.
Calculate the content of risperidone in the tablets.
| Time
(in min.) |
Mobile phase A
( per cent v/v) |
Mobile phase B
( per cent v/v) |
| 0 | 100 | 0 |
| 8 | 100 | 0 |
| 16 | 0 | 100 |
| 20 | 0 | 100 |
| 21 | 100 | 0 |
| 25 | 100 | 0 |
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:
mg: Miligram
ml: Milileter
inHg: Inch of Mercury
rpm: Rounds per minute
CFU: Colony forming unit
w/v: Weight/volume
HCl: Hydrochloric acid
