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% |
- Identification Test:
Shake a quantity of the powdered tablets containing 0.25g of sertraline Hydrochloride with 10ml of ethanol for 10 minutes, filter and evaporate the filtrate to dryness. On the residue, determine by infrared absorption spectrophotometry. Compare the spectrum with that obtained with Sertraline Hydrochloride reference standard or with the reference spectrum of Sertraline Hydrochloride.
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:
Diameter and thickness are determined by vernier in mm
8.0) Dissolution:
Apparatus: Paddle
Medium: 900ml of sodium acetate buffer solution pH 4.5,
Speed: 75rpm
Time: 30 minutes
Withdraw a suitable volume of the medium and filter.
Determine by liquid chromatography.
Test solution: Use the filtrate as given above
Reference solution: A solution of Sertraline HCl reference standard of the concentration similar to the test solution in the dissolution medium.
Chromatographic system:
- A stainless steel column 15cm X 4.6mm, packed with octadecylsilane bonded to porous silica (4µm),
- Mobile phase: a mixture of 15 volumes of methanol, 40 volumes of a solution containing 0.286 per cent v/v glacial acetic acid and 0.348 per cent v/v triethylamine and 45 volumes of acetonitrile,
- Flow rate: 1.8 ml per minute.
- Injection volume: about 20µl
- Spectrophotometer set at 265nm,
Inject the reference solution and the test solution.
Calculate the content of Sertraline.
Limit: NLT 80% of the stated amount of sertraline.
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:
Determine by liquid chromatography.
Solvent mixture: 30 volumes of acetonitrile and 70 volumes of water.
Test solution: Disperse a quantity of whole tablets containing 500mg of sertraline HCl with 150ml of the solvent mixture with the aid of ultrasound and dilute to 200ml with the solvent mixture and filter. Reference solution (a): Dilute 1.0 ml of the test solution to 500.0ml with the solvent mixture.
Reference solution (b): A 0.001 per cent w/v solution of ®-mandelic acid (sertraline impurity E) in the solvent mixture.
Reference solution (c): A 0.25 per cent w/v solution of Sertraline HCl Impurity reference standard in solvent mixture.
Reference solution (d): Dilute 1.0ml of reference solution (a) to 2.0 ml with the solvent mixture.
Chromatographic system:
- A stainless steel column 25cm X 4.6mm, packed with octadecylsilane bonded to porous silica (5µm),
- Mobile phase A: a 0.272 per cent w/v solution of potassium dihydrogen orthophosphate, adjusted to pH 3.0 with O.P.A.
B acetonitrile,
- A gradient programme using the conditions given below,
- Spectrophotometer set at 210nm,
- Flow rate: 1mlper minute,
- Injection volume: 20µl
| Time
(in min.) |
Mobile phase A
(per cent v/v) |
Mobile phase B
(per cent v/v) |
| 0 | 70 | 30 |
| 30 | 70 | 30 |
| 40 | 60 | 40 |
| 41 | 70 | 30 |
| 51 | 70 | 30 |
Inject reference solution (c). For peak identification of sertraline HCl impurity.
Inject reference solution (a), (b), (d) and the test solution. In the chromatogram obtained with the test solution, the area of any peak corresponding to sertraline impurity C (1 RS, 4 RS)-4-(4-chlorophenyl)-N-methyl-1,2,3,4-tetrahydronapthalen-1-amine) is not more than 4 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.8 per cent). The area of any peak corresponding to (R)-mandelic acid is not more than the area of any corresponding peak in the chromatogram obtained with reference solution (b) (0.4 per cent). The area of any other secondary peak is not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.2 per cent). The sum of areas of all the secondary peaks other than sertraline impurity C is not more than 7.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (1.5 per cent). Ignore any peak with an area less than that of the principal peak in the chromatogram obtained with reference solution (d) (0.1 per cent).
11.0) Enatiomeric purity:
Determined by liquid chromatography.
Test solution: Disperse a quantity of whole tablets containing 400mg of Sertraline HCl with 140ml of a mixture of 1 volume of acetonitrile and 2 volumes of watwer with the aid of ultasound and dilute to 200.0ml with a mixture of 1 volume of acetonitrile and 2 volumes of water, filter.
Reference solution (a): A 0.003 per cent w/v solution of Sertraline HCl cis-isomer reference standard in methanol (10.0 per cent).
Reference solution (b): A solution containing 0.0002 per cent w/v each of Sertraline HCl reference standard and Sertraline HCL cis-isomer Reference standard (1 RS, 4 RS)-4-(4-chlorophenyl)-N-methyl-1,2,3,4-tetrahydronapthalen-1-amine Reference standard) in methanol (10.0 per cent).
Chromatographic system:
- A stainless steel column 15cm X 4.6mm, packed with silica gel OD for chiral separation (such as Chrom tech chiral- AGP),
- Mobile phase: a mixture of 10 volumes of propan-2-ol and 90 volumes of a 0.23 per cent w/v solution of ammonium dihydrogen orthophosphate,
- Flow rate: 0.7 ml per minute.
- Injection volume: 40µl
- Spectrophotometer set at 210nm,
Inject reference solution (b). The test is not valid unless the resolution between the two principal peaks is not less than 2.5.
Inject reference solution (a) and the test solution. In the chromatogram obtained with the test solution, the area of any peak corresponsing to Sertraline cis-isomer is not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (1.5 per cent).
12.0) Assay: Determined by liquid chromatography.
Solvent mixture: A solution prepared by dissolving 6.8g of potassium dihydrogen orthophosphate and 0.9 g of sodium hydroxide in 1000ml of water and adjusting the pH to 6.8 with phosphoric acid or sodium hydroxide.
Test solution: Weigh and powder 20 tablets. Weigh a quantity of the powdered tablets containing about 80mg of atorvastatin, add 3ml to 5ml of water and disperse in sufficient methanol to produce a solution contyaining 0.016 per cent w/v of atorvasatin. Disperse with the aid of ultrasound, if required, and filter. Dilute the filtrate with sufficient of the solvent mixture to produce a solution containing 0.008 per cent w/v of atorvastatin.
Reference solution: Weigh a suitable quantity of atorvastatin calcium reference standard and dissolve in sufficient methanol to produce a solution containing 0.08 per cent of atorvastatin. To 5ml of this solution, add 20ml of methanol and dilute to 50ml with the solvent mixture to produce a solution containing 0.008 per cent w/v of atorvastatin.
Chromatographic system:
- A stainless steel column 25cm X 4.6mm, packed with octadecylsilane bonded to porous silica (5µm),
- Mobile phase: a mixture of 50 volumes of a buffer solution prepared by dissolving 1.54g of ammonium acetate in 1000ml of water and adjusting the pH to 4.0 with G.A.A. and 50 volumes of a mixture of 92.5 volumes of acetonitrile and 7.5 volumes of tetrahydrofurtan,
- Flow rate: 2 ml per minute.
- Injection volume: about 20µl
- Spectrophotometer set at 246nm,
Inject the reference solution. The test is not valid unless the column efficiency is not less than 2000 theoretical plates, the tailing factor is not more than 1.5 and the relative standard deviation for replicate injections is not more than 1.0 per cent.
Inject the reference solution and the test solution.
Calculate the content of Atorvastatin in the tablets.
Alternative Method: By UV Spectrophotometer
Test Solution: Weigh and powder 20 tablets. Weight sample equivalent to 25mg of Atorvastatin 100ml volumetric flask add 20ml methanol into it and sonicate to dissolve the test sample. Make up to mark with methanol. Filter and dilute 2ml of this solution to 50ml with methanol.
Reference Solution: Weigh 25mg of reference standard of Atorvastatin Calcium in 100ml of volumetric flask. Add 20ml methanol into it and sonicate to dissolve. Make up to mark with methanol. Dilute 1ml of this solution to 50ml with methanol.
Check Absorbance of test as well as reference standard at about 242nm in UV Spectrophotometer.
Calculate the content of Atorvastatin in the tablets.
Formula:
Area of Test STD Wt. (mg) 1 100 50 Potency
—————–X——————-X——X—————X——X———–X Average wt.
Area of STD 50 50 Test Wt. (mg) 2 100
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 rpm: Rounds per minute
mg: Miligram CFU: Colony forming unit
ml: Milileter G.A.A.: Glacial acetic acid
STD: Standard
inHg: Inch of Mercury
