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
|Average weight of tablets||Percentage deviation|
|More than 80mg but Less than 250mg||7.5%|
|250mg or More||5%|
4.0) Identification Test:
- Suspend a quantity of the powdered tablets containing 0.1 g of propranolol hydrochloride in 20 ml of water, filter, make the filtrate alkaline with 1 M sodium hydroxide and extract with three quantities, each of 10 ml, of ether. Wash the combined extracts with water until the washings are free from alkali, dry with anhydrous sodium sulphate, filter, and evaporate the filtrate to dryness and the residue at 50° at the pressure of 2 kPa for 1 hour.
On the residue, determine by infrared absorption spectrophotometry. Compare the spectrum with that obtained with propranolol hydrochloride reference standard treated in the same manner or with reference spectrum of propranolol.
When examined in the range 230nm to 360nm, the final solution obtained in assay shows absorption maxima at about 290 nm, 306nm, and 319 nm.
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
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 6.5g. For tablets with a unit weight of more than 650mg, 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.
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.
Medium: 900 ml of 0.1 M HCl.
Speed: 100 rpm
Time: 45 minutes.
Withdraw a suitable volume of the medium and filter. Dilute a suitable volume of the filtrate with the same solvent. Measure the absorbance of the resulting solution at the maximum at about 290 nm. Calculate the content of Propranolol HCl.
Limit: NLT 80% of the stated amount of Propranolol HCl.
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 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.
11.0) Related substances:
Determine by liquid chromatography.
Test solution: Disperse a quantity of powdered tablets containing about 100 mg of propranolol hydrochloride in 100ml of methanol and filter.
Reference solution: Dilute 1 ml of the test solution to 500 ml with mobile phase.
- A stainless steel column 20 cm x 5mm, packed with endcapped octadecylsilane bonded to silica (5µ) (such as hypersil ODS),
- Mobile phase: a mixture of 1.15 g of sodium dodecyl sulphate, 10 ml of mixture of 1 volume of sulphuric acid and 9 volumes of water, 20ml of a 1.7 per cent w/v solution of tetrabutylammonium dihydrogen orthophosphate, 370ml of water and 600 ml of acetonitrile, adjusted to pH 3.3 with 2 m sodium hydroxide,
- Flow rate: 1.8 ml per minute,
- Spectrophotometer set at 292 nm,
- Injection volume: 10µl.
Inject the reference solution and the test solution. Run the chromatogram 5 times the retention time of the principal peak. In the chromatogram obtained with the test solution, the area of any secondary peak is not more them the area of the principal peak in the chromatogram obtained with the reference solution (0.2 per cent )and the sum of the areas of all the secondary peaks is not more than four times the area of the principal peak in the chromatogram obtained with the reference solution (0.8per cent).
12.0) Uniformity of content:
(For tablets containing 10 mg or less)
Transfer one tablet to 100-ml volumetric flack, add 5ml of dilute hydrochloride acid and allow to stand, swirling occasionally, until it is disintegrated. Add about 70 ml of menthol and shake well for about 1 minute. Dilute to volume with methanol, mix and centrifuge an aliquot of the solution. Dilute a suitable volume of the clear solution with menthol to produce a solution containing 20µg of propranolol hydrochloride per ml. Measure the absorbance of the resulting solution at the maximum at about 290 nm (2.4.7), using methanol as the blank. Calculate the content of Propranolol HCl taking 206 as the specific absorbance at 290 nm.
Weigh and powder 20 tablets. Weigh a quantity of the powder containing about 20 mg Propranolol hydrochloride and shake with 20 ml of water for 10 minutes. Add 50 ml methanol, shake for a further 10 minutes, add sufficient methanol to produce 100.0 ml and filter. Dilute 10.0ml of the filtrate to 50.0 ml with methanol and measure the absorbance of
the resulting solution at the maximum at about 290 nm. Calculate the content of Propranolol HCl taking 206 as the specific absorbance at 290nm.
Acceptance criteria: 92.5%-107.5%
14.0) 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
inHg: Inch of Mercury
rpm: Rounds per minute
CFU: Colony forming unit
HCl: Hydrochloric acid