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:
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(c).
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: 900ml of a solution prepared by dissolving 7.21 gm of sodium lauryl sulpahte in 1000ml of water,
Time: 45 minutes
Speed: 50 rpm
Limit: NLT 75% of the stated amount of Atorvastatin and Fenofibrate.
Withdraw a suitable volume of the medium and filter.
Determine by liquid chromatography.
Test solution: Use the filtrate, dilute if necessary, with the dissolution medium.
Reference solution: Weigh a suitable quantity of atorvastatin calcium reference standard and fenofibrate reference standard and transfer to a 50.0ml volumetric flask. Dissolve with about 30ml of methanol and dilute to volume with methanol. Dilute suitable volume with the dissolution medium to obtain a solution having a known concentration similar to the concentration of the test solution.
Chromatographic system:
- A stainless steel column 25cmX4.6mm packed with octadecylsilane bonded to porous silica (5µm), (such as hypersil BDS C18)
- Mobile phase: a mixture of 35 volumes of buffer solution prepared by dissolving 6.8g of potassium dihydrogen orthophosphate in 1000ml of water, and adjusting the pH to 2.5 with O.P.A, 35 volumes of acetonitrile and 30 volumes of methanol.
- Flow rate: 1.5ml per minute,
- Spectrophotometer set at 280nm,
- Injection volume: 20µl
Inject the reference solution and test solution.
Calculate the content of Atorvastatin and fenofibrate in the medium.
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 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.
10.0) Related substance: Determined by liquid chromatography.
Test solution: Weigh and powder 20 tablets. Disperse a quantity of the powder containing 160mg of fenofibrate with 60ml of methanol, sonicate for 15 minutes, dilute to 250.0ml with the same solvent centrifuge at 2500 rpm for about 10 minutes, and filter. Dilute 10ml of the filtrate to 25ml with the mobile phase.
Reference solution (a): A 0.18 per cent w/v solution of atorvasatatin calcium reference standard in methanol. Dilute 5ml of this solution to 50 ml with methanol.
Reference solution (b): A 0.064 per cent w/v solution of fenofibrate reference standard in methanol.
Reference solution (c): Dilute 5ml reference solution (a) and 10.0ml of reference solution (b) to 25 ml with mobile phase.
Chromatographic system:
- A stainless steel column 25cmX4.6mm packed with octadecylsilane bonded to porous silica (5µm), (such as hypersil BDS C18)
- Mobile phase: a mixture of 35 volumes of a buffer solution prepared by dissolving 6.8g of potassium dihydrogen orthophosphate in 1000ml of water, adjusted to pH 2.5 with O.P.A., 35 volumes of acetonitrile and 30 volumes of methanol.
- Flow rate: 1.5ml per minute,
- Spectrophotometer set at 280nm,
- Injection volume: 50µl
Inject the test solution. The area of any secondary peak is not more than 1.0 per cent and the sum of the area of all the secondary peaks is not more than 2.0 per cent, calculated by area normalization.
11.0) Uniformity of content:
(For tablets containing 10mg or less)
Determine by liquid chromatography
Test solution: Disperse one tablet in 30ml of methanol, sonicate for 15 minutes, dilute to 50ml with same solvent, centrifuge at 2500 rpm for about 10 minutes, and filter. Dilute 5ml of this solution tom 25ml with the mobile phase.
Reference solution: A 0.08 per cent w/v solution of atorvastatin reference standard in methanol. Dilute 5ml of this solution to 100ml with the mobile phase.
Chromatographic system:
- A stainless steel column 25cmX4.6mm packed with octadecylsilane bonded to porous silica (5µm), (such as hypersil BDS C18)
- Mobile phase: a mixture of 35 volumes of a buffer solution prepared by dissolving 6.8g of potassium dihydrogen orthophosphate in 1000ml of water, adjusted to pH 2.5 with O.P.A., 35 volumes of acetonitrile and 30 volumes of methanol.
- Flow rate: 1.5ml per minute,
- Spectrophotometer set at 280nm,
- Injection volume: 20µl
Calculate the content of Atorvastatin in the tablet.
12.0) Assay: Determined by liquid chromatography.
Test solution: Weigh and powder 20 tablets. Disperse a quantity of the powder containing 160mg of fenofibrate with 60ml of methanol, sonicate for 15 minutes, dilute to 250.0ml with the same solvent centrifuge at 2500 rpm for about 10 minutes, and filter. Dilute 10ml of the filtrate to 25ml with the mobile phase.
Reference solution (a): A 0.18 per cent w/v solution of atorvasatatin calcium reference standard in methanol. Dilute 5ml of this solution to 50 ml with methanol.
Reference solution (b): A 0.064 per cent w/v solution of fenofibrate reference standard in methanol.
Reference solution (c): Dilute 5ml reference solution (a) and 10.0ml of reference solution (b) to 25 ml with mobile phase.
Chromatographic system:
- A stainless steel column 25cmX4.6mm packed with octadecylsilane bonded to porous silica (5µm), (such as hypersil BDS C18)
- Mobile phase: a mixture of 35 volumes of a buffer solution prepared by dissolving 6.8g of potassium dihydrogen orthophosphate in 1000ml of water, adjusted to pH 2.5 with O.P.A., 35 volumes of acetonitrile and 30 volumes of methanol.
- Flow rate: 1.5ml per minute,
- Spectrophotometer set at 280nm,
- Injection volume: 20µl
Inject reference solution(c). The test is not valid unless the resolution between atorvastatin and fenofibrate peaks is not less than 27, the column efficiency is not less than 7000 theoretical plates, the tailing factor is not more than 2.0 and the relative standard deviation of replicate injections is not more than 2.0 per cent for atorvastatin peak.
Inject the reference solution (c) and test solution.
Calculate the content of Atorvastatin and fenofibrate in tablets.
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
mg: Miligram
ml: Milileter
STD: Standard
inHg: Inch of Mercury
rpm: Rounds per minute
CFU: Colony forming unit
O.P.A.: Orthophopsphoric acid
w/v: Weight/Volume
