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:
Extract a quantity of the powdered tablets containing 0.5gm of Paracetamol with 20ml of acetone, filter, evaporate the filtrate to dryness and dry at 105°. The residue complies with the following tests.
- Determined by Infrared absorption spectrometry. Compare the spectrum with that obtained with Paracetamol reference standard or with the reference spectrum of Paracetamol.
- Boil 0.1 gm in 1 ml of hydrochloric acid for 3 minutes, add 10ml of water and cool; no precipitate is produced. Add 0.05ml of 0.0167M potassium dichromate; a violet color develops which does not turn red.
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) 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: 900ml of phosphate buffer pH 5.8
Speed: 50 rpm
Time: 30 min
Limit: NLT 85% of the labeled amount of Paracetamol is dissolved.
Withdraw a suitable volume of the medium and filter and dilute a suitable volume of the filtrate with the same solvent. Measure the absorbance of the resulting solution at the maximum at about 243nm. Similarly measure the absorbance of a solution of known concentration of Paracetamol reference solution. Calculate the content of Paracetamol.
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.
Test solution: Disperse a quantity of powdered tablets containing about 0.2gm of Paracetamol in 10.0ml of the mobile phase, filter.
Reference solution (a): Dilute 1ml of the test solution to 20ml with the mobile phase. Dilute 1 ml of this solution to 20ml with the mobile phase.
Reference Solution (b): A solution containing 0.002 percent w/v each of 4-aminophenol and Paracetamol reference solution in the mobile phase.
Reference solution(c): A 0.00002 percent w/v solution of 4-chlorocetanilide in the mobile phase.
Chromatography system:
- A stainless steel column 25cm X 4.6mm, packed with octysilane bonded to porous silica (5µl)
- Column temperature: 35°
- Mobile phase: a mixture of 25 volumes of methanol containing 1.15gm of tetrabutylammonium hydroxide solution (40%w/v) with 37.5 volumes of 0.05M disodium hydrogen orthophosphate and 37.5 volumes of 0.05 M sodium dihydrogen orthophosphate.
- Flow rate: 1.5ml per minute
- Spectrophotometer set at 245nm
- Injection volume: 20µl
Inject reference solution (b). The test is not valid unless the resolution between the two principal peaks is not less than 4.0.
Inject reference solution (a) and the test solution, (b) and (c). Run the chromatogram 12 times the retention time of the principal peak. In the chromatogram obtained with the test solution the area of peak corresponding to 4-aminophenol is not more than the area of the corresponding peak in reference solution (b) (0.1%), the area of peak corresponding to 4-chloroacetanilide is not more than the area of the principal peak in reference solution (c) (10ppm) and the area of any other secondary peak is not more than the area of the principal peak obtained with reference solution (a) (0.25%)
12.0) Assay:
Weigh and powder 20 tablets. Weigh a quantity of the powder containing about 0.15gm of Paracetamol, add 50ml of 0.1 M sodium hydroxide, dilute with 100ml of water, shake for 15 minutes and add sufficient water to produce 200ml. Mix filter and dilute 10ml of the filtrate to 100ml with water. To 10ml of resulting solution add 10ml of 0.1 M sodium hydroxide, dilute to 100ml with water and mix. Measure the absorbance of the resulting solution at the maximum at about 257nm. Calculate the content of Paracetamol taking 715 as the specific absorbance at 257nm.
Acceptance criteria: 95.0%-105.0%
Formula:
Absorbance of test 1000 200 100 100
———————-X————–X——————-X————X————X Average weight
715 100 Test Wt.(mg) 10 10
