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%
|Average weight of tablets||Percentage deviation|
|More than 80mg but Less than 250mg||7.5%|
|250mg or More||5%|
4.0) Identification Test:
- Shake a quantity of powdered tablets containing about 5mg of nortriptyline with 20ml of methanol and filter. To 1ml of filtrate add 1ml of a 2.5 per cent w/v solution of sodium bicarbonate, 1ml of a 2 per cent w/v solution of sodium periodate and 1ml of a 0.3 per cent w/v solution of potassium permanganate. Allow to stand for 15 minutes for 15 minutes, acidify with 1 M sulphuric acid and extract with 10ml of 2,2,4-trimethyl-pentane.When examined in the range 230nm to 360nm, the resulting tromethylpentane solution shows an absorption maximum only at about 265nm.
- Triturate a quantity of the powdered tablets containing 0.1 gm of nortriptyline with 10ml of chloroform, filter and evaporate the filtration to a low volume. Add ether until a turbidity is produced and allow to stand. Dissolve 50mg of the precipitation in 3ml of warm water, cool and add 1 drop of a 2.5 per cent w/v solution of quinhydrone in methanol; a red colour is produced after a few minutes (distinction from amitriptyline).
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) 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.
9.0) Related substance: Determined by thin layer chromatography, coating the plate with silica gel G.
Mobile phase: A mixture of 85 volumes of cyclohexane, 15 volumes of ethyl acetate and 3 volumes of diethylamine.
Test solution: Extract a quantity of the powdered tablets containing 20mg of Nortriptyline with 5ml of a mixture of 9 volumes of ethanol (95 per cent) and 1 volume of 2 M hydrochloric acid, centrifuge and use the supernatant liquid.
Reference solution: A 0.001 per cent w/v solution of dibenzosuberone reference standard in ethanol (95 per cent) prepared in subdued light. Apply to the plate 5µl of each solution. Allow the mobile phase to rise 14cm in an unsaturated tank protected from light. Dry the plate in air, spray with a freshly prepared solution of sulphuric acid containing 4 per cent v/v of formaldehyde solution and examine immediately under ultraviolet light at 365nm. Any secondary spot in the chromatogram obtained with the test solution is not more intense than the spot in the chromatogram obtained with the reference solution.
10.0) Uniformity of content:
For tablets containing 10mg or less. Determine by liquid chromatography.
Test solution: Transfer one tablet to 100.0ml of volumetric flask, add about 5ml of water and disperse with the aid of ultrasound. Add about 50.0ml of methanol, mix with the aid of ultrasound for 30 minutes and dilute to 100.0 ml with water. Centrifuge and use the supernatant liquid. Dilute if necessary.
Reference solution: A 0.01 per cent w/v solution of nortriptyline hydrochloride reference standard in methanol (50 per cent).
Follow the procedure given in the assay. Calculate the content of Nortriptyline in tablet.
11.0) Assay: Determined by liquid chromatography.
Test solution: Shake vigorously 20 tablets with 50ml of water until the tablets disintegrate completely, add 100ml of methanol and shake for 30 minutes. Add sufficient water to produce 200ml, filter and dilute a volume of filtrate containing about 25mg of nortriptyline to 100ml with methanol (50 per cent).
Reference solution: A 0.025 per cent solution of nortriptyline HCl reference standard in methanol (50 per cent).
- A stainless steel column 20cmX4.6mm packed with octadecylsilane bonded to porous silica (10µm),
- Mobile phase: A 0.56 per cent w/v solution of sodium hexanesulphonate in a mixture of equal volumes of water and acetonitrile adjusted to pH 4.5 with glacial acetic acid.
- Flow rate: 2ml per minute,
- Spectrophotometer set at 239nm,
- Injection volume: 20µl
Inject reference solution and the test solution.
Calculate the content of Nortriptyline in the tablet.
Alternative Method: By UV Spectrophotometer
Test Solution: Weigh and powder 20 tablets. Weight sample equivalent to 50mg of Nortriptyline 100ml volumetric flask add 20ml 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 1ml of this solution to 50ml in same 0.1 M HCl.
Reference Solution: Weigh 50mg of reference standard of Nortriptyline HCl in 100ml of volumetric flask. Add 20ml 0.1 M HCl into it and sonicate to dissolve. Dilute 1ml of this solution to 50ml with same solvent.
Check Absorbance of test as well as reference standard at about 296nm in UV Spectrophotometer.
Calculate the content of Nortriptyline in the tablets.
Area of Test STD Wt.(mg) 1 100 50 Potency
—————–X————–X——-X—————X——–X———–X Average wt.
Area of STD 100 50 Test Wt.(mg) 1 100
inHg: Inch of Mercury
rpm: Rounds per minute
CFU: Colony forming unit
G.A.A: Glacial acetic acid
O.P.A: Orthophosphoric acid
HCl: Hydrochloric acid