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% |
4.0) Identification Test:
In the assay, the principal peaks in the chromatogram obtained with the test solution corresponds to the peaks in the chromatogram obtained with reference solution (c) of Losaratn potassium and hydrochlorothiazide.
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 water,
Speed: 100 rpm
Time: 30 minutes
Limit: NLT 75% of the labeled amount of Losartan Potassium and Hydrochlorothiazide is dissolved.
Withdraw a suitable volume of the medium and filter.
Determine by liquid chromatography,
Test solution: Use the filtrate obtained above.
Reference solution (a): A 0.05 per cent w/v solution of Losartan Potassium reference standard in dissolution medium.
Reference solution (b): Dissolve about 25mg of hydrochlorothiazide reference standard in 10ml of acetonitrile and dilute to 100ml with dissolution medium.
Reference solution (c): Dilute 10ml of reference solution (a) and 5ml of reference solution (b) to 100ml with dissolution medium.
Chromatographic system:
- A stainless steel column 30cm X3.9mm, packed with octadecylsilane bonded to porous silica (10µm).
- Mobile phase: a mixture of 60 volumes of buffer solution prepared by dissolving 0.78g of sodium dihydrogen orthophosphate in 500ml of water, adjusted to pH 2.5 with O.P.A. and 40 volumes of acetonitrile.
- Flow rate: 1ml per minute.
- Spectrophotometer set at 220nm,
- Injection volume: about 20µl
Inject reference solution (c). The test is not valid unless the tailing factor of the both the principal peaks 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 Losartan potassium and Hydrochlorothiazide in the dissolution 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 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) Uniformity of content:
Determine by liquid chromatography,
For hydrochlorothiazide:
Test solution: Disperse 1 whole tablet in 100ml of the mobile phase. Dilute 5ml of this solution to 50ml with the mobile phase.
Reference solution: A 0.025 per cent w/v solution of hydrochlorothiazide reference standard in the mobile phase. Dilute 5ml of this solution to 10ml with the mobile phase.
Chromatographic system:
- A stainless steel column 30cm X3.9mm, packed with octadecylsilane bonded to porous silica (10µm).
- Mobile phase: a mixture of 60 volumes of buffer solution prepared by dissolving 0.78g of sodium dihydrogen orthophosphate in 500ml of water, adjusted to pH 2.5 with O.P.A. and 40 volumes of acetonitrile.
- Flow rate: 1ml per minute.
- Spectrophotometer set at 220nm,
- Injection volume: about 20µl
Inject the reference solution. The test is not valid unless 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.
Calculate the content of Hydrochlorothiazide.
Inject the reference solution and the test solution.
11.0) Assay: Determined by liquid chromatography.
Test solution: Weigh and powder 20 tablets. Disperse a quantity of powder containing about 50mg of Losartan potassium and 12.5 mg of hydrochlorothiazide in 100ml of the mobile phase, filter. Dilute 5ml of the filtrate to 50ml with the mobile phase.
Reference solution (a): A 0.05 per cent w/v solution of Losartan potassium reference standard in the mobile phase.
Reference solution (b): A 0.025 per cent w/v solution of hydrochlorothiazide reference standard in the mobile phase.
Reference solution (c): Dilute 10ml of reference solution (a) and 5ml of reference solution (b) to 100ml with mobile phase.
Chromatographic system:
- A stainless steel column 30cm X3.9mm, packed with octadecylsilane bonded to porous silica (10µm).
- Mobile phase: a mixture of 60 volumes of buffer solution prepared by dissolving 0.78g of sodium dihydrogen orthophosphate in 500ml of water, adjusted to pH 2.5 with O.P.A. and 40 volumes of acetonitrile.
- Flow rate: 1ml per minute.
- Spectrophotometer set at 220nm,
- Injection volume: about 20µl
Inject reference solution (c). The test is not valid unless the tailing factor is not more than 2.0 and relative standard deviation for replicate injections is not more than 2.0 per cent.
Inject the reference solution (c) and test solution.
Calculate the content of Losartan Potassium and hydrochlorothiazide in the tablets.
Acceptance criteria: 90.0%-110.0%
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:
mg: Miligram
ml: Milileter
inHg: Inch of Mercury
rpm: Rounds per minute
CFU: Colony forming unit
w/v: Weight/volume
