- Description: Visual.
- 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 the 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 in each of the basket and if the tablet has a soluble external coating, immerse the basket in water at room temperature for 5 minutes. Then operate the apparatus using simulated gastric fluid temperature maintained at 37±2° as the immersion fluid. After 2 hour of operation in simulated gastric fluid, lift the basket from the fluid, and observe the tablets. The tablets show no evidence of disintegration, cracking, or softening. Operate the apparatus, using simulated intestinal fluid temperature maintained at 37±2° as the immersion fluid, for the time specified in the monograph. Lift the basket from the fluid and observe the tablets. All of the tablets disintegrate 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: 0.1 M hydrochloric acid; 900ml
Speed: 50 rpm
Time: 45 min
Withdraw a suitable volume of the medium and filter
Determined by liquid chromatography
Solvent mixture: A mixture of equal volumes of acetonitrile and water.
Test solution: Use the filtrate obtained above.
Reference Solution: Dissolve a quantity of Olmesartan medoxomil reference standard in acetonitrile and dilute with the dissolution medium to obtain a solution of known concentration similar to the expected concentration of the test solution.
Chromatographic system:
- A stainless steel column 15cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µm), (such as Inertsil ODS3V)
- Mobile Phase: A mixture of 60 volumes of buffer solution prepared by dissolving 6.8 gm KH2PO4 in 1000ml of water, adjusted to pH 3.5 with orthophorphoric acid and 40 volume of acetonitrile.
- Flow rate: 1ml per minute,
- Spectrophotometer set at 215nm,
- Injection volume: 10µl
Inject the reference solution and the test solution.
Calculate the content of Olmesartan medoxomil in the medium.
Limit: NLT 75% of the stated amount of Olmesartan medoxomil.
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 substances: Determined by liquid chromatography.
NOTE: Use freshly prepared test solution.
Solvent mixture: Equal volumes of acetonitrile and buffer solution prepared by dissolving 3.4gm of potassium dihydrogen orthophosphate in 1000ml of water, add 1ml of triethylamine, adjusted to pH 2.5 with orthophosphoric acid.
Test Solution: Weigh and powder 20 tablets. Disperse a quantity of powder containing 100mg of olmesartan medoxomil in 100ml of solvent mixture, with the aid of ultrasound for 20 minutes, and dilute to 200ml with the solvent mixture and filter.
Reference solution: A 0.00025 percent w/v solution of olmesartan medoxomil reference solution in the solvent mixture.
Chromatographic system:
- A stainless steel column 25cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µm) (such as intersil ODS 3V)
- Mobile Phase: A mixture of 65 volumes of buffer solution prepared by dissolving 3.4gm of potassium dihydrogen orthophosphate in 1000ml of water, add 1ml of triethylamine. Adjusted to pH 2.5 with orthophosphoric acid and 35 volumes of acetonitrile.
- Flow rate: 1ml per minute,
- Spectrophotometer set at 215nm,
- Injection volume: 20µl
The relative retention time of olmesartan with respect to olmesartan medoxomil is 0.25 and the correction factor is 0.83.
Inject the reference solution. The test is not valid unless the column efficiency is not less than 1500 theoretical plates, the tailing factor is not more than 2.0.
Inject the reference solution and the test solution. In the chromatogram obtained with test solution, the area of peak due to olmesartan is not more than 6 times the area of the principal peak in the chromatogram obtained with reference solution (3.0 per cent). The area of any other secondary peak is not more than the area of the principal peak in the chromatogram obtained with the reference solution (0.5 per cent) and the sum of the areas of all the secondary peaks other than olmesartan peak is not more than four times the area of the principal peak in the chromatogram obtained with the reference solution (2.0 per cent). Ignore any peak with an area less than 0.1 times the area of the principal peak in the chromatogram obtained with the reference solution (0.05 per cent).
11.0) Assay: Determined by liquid chromatography.
Solvent mixture: Equal volumes of acetonitrile and buffer solution prepared by dissolving 3.4gm of potassium dihydrogen orthophosphate in 1000ml of water, add 1ml of triethylamine adjusted to pH 2.5 with O.P.A.
Test solution: Weigh and powder 20 tablets. Disperse a quantity of powder containing 200mg of Olmesartan Medoxomil in 150ml of solvent mixture, with the sid of ultrasound for 20 minutes, and dilute to 250.0ml with the solvent mixture. Dilute 5.0ml of this solution to 100.0ml with the solvent mixture.
Reference solution: A 0.004 per cent w/v solution of Olmesartan medoxomil reference standard in the same solvent.
Chromatographic system:
- A stainless steel column 15cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µm), (such as Inertsil ODS 3V)
- Mobile Phase: A mixture of 55 volumes of buffer solution prepared by dissolving 3.4 gm of potassium dihydrogen orthophosphate in 1000ml of water, add 1ml of triethylamine. Adjusted to pH 2.5 with O.P.A. and 45 volumes of acetonitrile
- Flow rate: 1ml per minute,
- Spectrophotometer set at 215nm,
- Injection volume: 10µl
Inject the reference solution. The test is not valid unless the column efficiency is not less than 1500theoretical 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 the reference solution and the test solution.
Calculate the content of Olmesartan medoxomil in the tablets.
Acceptance criteria: 90.0%-110.0%
Formula for calculation:
Area of Test STD Wt.(mg) 5 250 100 Potency
—————–X————–X———X—————–X——X———–X Average weight
Area of STD 100 50 Test Wt.(mg) 5 100
12.0) 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
