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 peaks in the chromatogram obtained with the test solution corresponds to the principal peaks in the chromatogram obtained with reference solution.
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. 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 for most tablets.
9.0) Dissolution:
Apparatus: Paddle
Medium: 500ml of 0.01 M HCl
Speed: 75 rpm
Time: 45min.
Limit: NLT 80% of the stated amount of Amlodipine.
Withdraw a suitable volume of the medium and filter, rejecting the first few ml of the filtrate.
Test solution: Use filtrate, dilute if necessary, with the dissolution medium.
Reference solution (a): A solution of amlodipine beslate reference solution containing 0.02 per cent w/v of amlodipine in methanol.
Reference solution (b): A solution of 0.08 per cent w/v of temlisartan reference standard in methanol.
Reference standard (c): Dilute reference solution (a) and (b) with dissolution medium to obtain a solution having a known concentration similar to the test solution.
Chromatographic system:
- A stainless steel column 15m X4.6mm, packed with encapped octadecylsilane bonded to porous silica (5µ),
- Mobile Phase: a mixture of 60 volumes of a buffer slution prepared by dissolving 2.72gm potassium dihydrogen orthophosphate in 1000ml of water and adjusted to pH 2.4 with O.P.A. and 40 volumes of acetonitrile
- Flow rate: 1ml per minute,
- Spectrophotometer set at 237nm,
- Injection volume: 10µl
Inject reference solution (c). The test is not valid unless the column efficiency for both the analyte peak is not less than 1500 theoretical plates, the tailing factor is not more than 2.0 and the relative standard deviation for replicate injections is not more than 2.0 per cent.
Inject reference solution (c) and the test solution.
Calculate the content of Amlodipine and Telmisartan.
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.
Solvent mixture: 10 volumes of 0.1 M HCl and 90 volumes of methanol.
Test solution: Weigh and powder 20 tablets into fine powder. Transfer the powder containing 25mg of amlodipine into 100.0ml volumetric flask and dissolve in about 70.0ml solvent mixture and sonicate for 45 minutes. After sonication bring the solution into room temperature and dilute to volume up to the mark with solvent mixture.
Reference solution (a): A 0.004 per cent w/v solution of telmisartan reference standard in solvent mixture.
Reference solution (b): A solution of amlodipine beslate reference standard containing 0.00125 per cent w/v of amlodipine in solvent mixture.
Reference solution (c): Transfer 5ml of reference solution (a) and 2ml of reference solution (b) in 100.0ml volumetric flask and dilute to volume upto tha mark with solvent mixture and mix.
Chromatographic system:
- A stainless steel column 15cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µ),
- Mobile Phase: A. a mixture of 85 volumes of a buffer solution prepared by dissolving 1.36g of potassium dihydrogen orthophosphate in 1000.0ml of water and adjusted to pH 3.2 with O.P.A. and 15 volumes of acetonitrile
- a mixture of 15 volumes of a buffer solution prepared by dissolving 1.36 g of potassium dihydrogen orthophosphate in 1000.0ml of water and adjusted to pH 3.2 with O.P.A. and 85 volumesn of acetonitrile.
- A gradient programme using the conditions given below.
- Flow rate: 1.5 per minute,
- Spectrophotometer set at 237 nm,
- Injection volume: 25µl
Inject reference solution (c). The test is not valid unless the column efficiency for both the peak is not less than 1500 theoretical plates, the tailing factor is not more than 2.0 and the relative standard deviation for replicate injections is not more than 5.0 per cent.
The relative retention time with reference to amlodipine for impurity D(3-ethyl 5-methyl 2-[(2-aminoethoxy) methyl]-4-(2-chlorophenyl)-6-methylpyridine-3, 5-dicarboxylate) is 0.5. Multiply the peak area of impurity D by correction factor 2.58.
| Time
( in min ) |
Mobile phase A
( per cent v/v ) |
Mobile phase B
( per cent v/v) |
| 0 | 85 | 15 |
| 7 | 85 | 15 |
| 15 | 90 | 10 |
| 20 | 75 | 25 |
| 35 | 60 | 40 |
| 40 | 55 | 45 |
| 45 | 45 | 55 |
| 50 | 35 | 65 |
| 55 | 85 | 15 |
| 60 | 85 | 15 |
Inject reference solution (c) and the test solution. In the chromatogram obtained with the test solution, the area of an peak due to impurity D of amlodipine is not more than 10 times the area of the amlodipine principal peak in reference solution (c) (1.0 per cent). The area of an secondar peak due to amlodipine and telmisartan is not more than 5 times the area of the amlodipine principal peak in reference solution (c) (0.5 per cent) and the sum of the areas of all the secondary peak xcluding impurity D is not more than 20 times the area of the principal peak of amlodipine in the chromatogram obtained with reference solution (c) (2.0 per cent). Ignore any peaks with an area less than 0.5 times the principal peak as the chromatogram obtained with reference solution(c) (0.05 per cent).
12.0) Uniformity of content: Determined by liquid chromatography.
Use chromatographic conditions, reference solution, solvent mixture and system suitability as under assay.
Test solution: Transfer 1 tablet into 100ml volumetric flask add about 5.0ml of mobile phase and sonicate to disperse whole tablet completely, add about 70.0ml of solvent mixture and sonicate for 90 minutes. Afetr sonication bring the solution into room temperature and dilute up to the mark with solvent mixture, mix and filter. Dilute 5.0ml of this solution to 25.0ml with solvent mixture and mix.
Inject reference solution (c) and test solution.
Calculate the content of Amlodipine in tablet.
13.0) Assay: Determined by liquid chromatography.
Solvent mixture: 10 volumes of 0.01 M HCl and 90 volumes of methanol.
Test solution: Weigh and powder 20 tablets. Disperse a quantity of powder containing 5mg of amlodipine in 50.0ml volumetric flak, add about 5ml of mobile phase and sonicate add 30.0ml of solvent mixture and sonicate. After sonication dilute up to the mark with solvent mixture and mix. Dilute 5.0ml of this solution to 50.0ml with solvent mixture and mix.
Reference solution (a): A 0.008 per cent w/v solution of telmisartan reference standard in solvent mixture.
Reference solution (b): A solution of amlodipine besylate reference standard containing 0.02 per cent w/v solution of amlodipine reference standard in solvent mixture.
Reference soution (c): Dilute reference solution (a) and (b) with the solvent mixture to obtain a solution having a known concentration similar to the test solution.
Chromatographic system:
- A stainless steel column 25cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µ),
- Mobile Phase: a mixture of 60 volums of a buffer solution prepared by dissolving 2.72g potassium dihydrogen orthophosphate in 1000ml water and adjusted to pH 3.0 with O.P.A. and 40 volumes of Acetonitrile.
- Flow rate: 1ml per minute
- Spectrophotometer set at 237 nm,
- Injection volume: 20µl
Inject the reference solution(c). The test is not valid unless the column sfficiency for both the analyte peak is not less than 2000 theoretical plates, the tailing factor is not more than 2.0 and the relative standard deviation for replicate injections is not more than 2.0 per cent.
Inject reference solution(c) and the test solution.
Calculate the content of Amlodipine and Telmisartan in tablet.
Acceptance criteria: 90.0%-110.0%
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
Abbreviations:
Wt.: Weight
mg: Miligram
ml: Milileter
STD: Standard
inHg: Inch of Mercury
rpm: Rounds per minute
CFU: Colony forming unit
O.P.A.: Orthophosphoric acid
w/v: Weight/volume
HCl: Hydrochloric acid
