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 peak in the chromatogram obtained with the test solution corresponds to the peak 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 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 1.0 per cent w/v solution of sodium lauryl sulphate in cito-phosphate buffer solution prepared by dissolving 4.1363 g of disodium hydrogen phosphate and 0.475g of citric acid monohydrate in 200ml water, add 0.125ml of othophosphoric acid and dilute with water to 1000ml. Adjust the pH to 6.8 with 2 M sodium hydroxide or orthophosphoric acid as required.
Time: 45 minutes
Speed: 75 rpm
Limit: NLT 75% of the stated amount of Cilnidipine.
Withdraw a suitable volume of medium and filter. Reject the first few ml of the filtrate and dilute a suitable volume of the filtrate with dissolution medium. Measure the absorbance of the filtered solution at the maximum at about 243nm. Calculate the content of cilnidipine in the medium from the absorbance obtained from a solution of known concentration of cilnidipine reference standard prepared by dissolving weighed quantity of cilnidipine reference standard in methanol and diluting further with 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) Related substances: Determine by liquid chromatography.
Test solution: Weigh a quantity of the powdered tablets containing 50mg of cilnidipine, disperse in 20ml methanol with the aid of ultrasound for 20 minutes with intermediate shaking and dilute to 50.0ml with mobile phase A, centrifuge and filter.
Reference solution: A 0.0002 per cent w/v solution of cilnidipine reference standard prepared by dissolving weighed quantity of cilnidipine reference standard completely in methanol and diluting further with the mobile phase A.
Chromatographic system:
- A stainless steel column 25cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µm), (such as phenomenex-kinetex)
- Mobile phase A: A mixture of 35 volumes of a buffer solution prepared by dissolving 2.0g of ammonium dihydrogen phosphate in 1000ml of water, adjusted to pH 3.0 with dilute O.P.A. and 65 volumes of methanol.
- A mixture of 40 volumes of a buffer solution prepared by dissolving 2.0 g of ammonium dihydrogen phosphate in 1000ml of water, adjusted to pH 3.0 with dilute phosphoric acid and 60 volumes of acetonitrile.
- Flow rate: 1ml per minute.
- A gradient programme using the conditions given below
- Spectrophotometer set at 245nm,
- Injection volume: about 10µl
Inject the reference solution. The test is not valid unless the column efficiency is not less than 3000 theoretical plates, the tailing factor is not more than 20 and relative standard deviation for replicate injections is not more than 5.0 per cent.
Inject the reference solution and the test solution. In the chromatogram obtained with the test solution, the area of any secondary peak is not more than 2.5 times the area of the principal peak in the chromatogram obtained with reference solution (0.5 per cent) and the sum of area of all the secondary peaks is not more than 5 times the area of the principal peak of Cilnidipine in the chromatogram obtained with reference solution (1.0 per cent).
| Time
(in min) |
Mobile phase A
( per cent v/v) |
Mobile phase B
(per cent v/v) |
| 0 | 45 | 55 |
| 12 | 45 | 55 |
| 20 | 35 | 65 |
| 28 | 35 | 65 |
| 45 | 35 | 65 |
| 55 | 45 | 55 |
| 60 | 45 | 55 |
11.0) Uniformity of content:
Test solution: Disperse one tablet in 50ml solvent mixture with the aid of ultrasound for 15 minutes with intermediate shaking and dilute to volume to obtain a solution containing 0005 per cent w/v of cilnidipine in solvent mixture.
Reference solution: A 0.005 per cent w/v solution of cilnidipine reference standard in the solvent mixture.
Chromatographic system:
- A stainless steel column 15cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µm) ( such as YMC ODS-AM),
- Mobile phase: a mixture of 25 volumes of a buffer solution prepared by dissolving 20 g of ammonium dihydrogen phosphate in 1000ml of water, adjusted to pH 30 with dilute O.P.A. and 75 volumes of methanol
- Flow rate: 1ml per minute,
- Spectrophotometer set at 245nm,
- Injection volume: 10µl
- Column temperature: 40°
Calculate the content of Cilnidipine in the tablet.
12.0) Assay: Determined by liquid chromatography.
Solvent mixture: 40 volumes of acetonitrile, 40 volume of methanol and 20 volumes of a buffer solution prepared by dissolving 2.0 gm of ammonium dihydrogen phosphate, in 1000ml
of water, adjusted to pH 3.0 with 10 per cent w/v solution of othophosphoric acid.
Test solution: Weigh and powder 20 tablets. Weigh accurately a quantity of the powder containing about 100mg Cilnidipine, disperse in 50ml solvent mixture with the aid of ultrasound for 15 minutes and dilute to 100ml with solvent mixture and filter. Dilute 5ml of the filtration to 100ml with the solvent mixture.
Reference solution: A 0.005 per cent w/v solution of cilnidipine reference standard in the solvent mixture.
Chromatographic system:
- A stainless steel column 15cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µm) ( such as YMC ODS-AM),
- Mobile phase: a mixture of 25 volumes of a buffer solution prepared by dissolving 20 g of ammonium dihydrogen phosphate in 1000ml of water, adjusted to pH 30 with dilute O.P.A. and 75 volumes of methanol
- Flow rate: 1ml per minute,
- Spectrophotometer set at 245nm,
- Injection volume: 10µl
- Column temperature: 40°
Inject the reference solution. The test is not valid unless the column efficiency is not less than 2000 theoretical plates and 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 Cilnidipine in the tablets.
Alternative Method: By UV Spectrophotometer
Test Solution: Weigh and powder 20 tablets. Weight sample equivalent to 25mg of Cilnidipine 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 in same solvent.
Reference Solution: Weigh 25mg of reference standard of Cilnidipine in 100ml of volumetric flask. Add 20ml methanol into it and sonicate to dissolve. Dilute 2ml of this solution to 50ml with methanol.
Check Absorbance of test as well as reference standard at about 240nm in UV Spectrophotometer.
Calculate the content of Cilnidipine in the tablets.
Formula:
Abs. of Test STD Wt.(mg) 2 100 50 Potency
—————–X————–X——-X—————X——–X———–X Average wt.
Abs. of STD 100 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
mg: Miligram
ml: Milileter
STD: Standard
inHg: Inch of Mercury
rpm: Rounds per minute
CFU: Colony forming unit
HCl: Hydrochloric acid
w/v: Weight/Volume
Abs. Absorbance
O.P.A.: Orthophosphoric acid
