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 assay, the principal peaks in the chromatogram obtained with the test solution correspond 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) Dimension of Tablet:
Length, breadth and thickness are determined by vernier in mm
7.0) 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.
8.0) Dissolution:
- For Metformin HCl
Apparatus: Basket
Medium: 900ml of a 0.68 per cent w/v solution of potassium dihydrogen phosphate, adjust to pH 6.8 by addition of 1M sodium hydroxide.
Time: 1st hour, 4th hour, 8th hour
Speed: 100 rpm
Limit: For 1st Hour: 25%-45%
For 4th Hour 45%-75%
For 8th Hour NLT 80%
Withdraw a suitable volume of the medium and filter, dilute suitably with water and measure the absorbance of the resulting solution at the maximum at about 233nm. Calculate the content of Metformin HCl, in the medium taking 806 as the specific absorbance at 233nm.
- For Glimepiride
Apparatus: Paddle
Medium: 900ml of a buffer solution prepared by dissolving 0.58gm of monobasic potassium phosphate and 8.86 gm of anhydrous dibasic sodium phosphate in 1000ml of water and adjust to pH 7.8 with OPA or 1M sodium hydroxide, add 10gm of sodium lauryl sulphate and mix.
Time: 90 minutes
Speed: 100 rpm
Limit: NLT 75% of the stated amount of Glimepiride.
Withdraw a suitable volume of the medium and filter. Dilute further, with the dissolution medium.
Determined by liquid chromatography.
Solvent mixture: A mixture of 90 volumes of acetonitrile and 10 volumes of water.
Test solution: Dilute the filtrate if necessary, with the dissolution medium.
Reference solution: Weigh accuratel 10mg of glimepiride reference solution in 100ml volumetric flask and dilute with solvent mixture and sonicate. Dilute further with dissolution medium to obtain a solution containing 0.001 per cent w/v solution of glimepiride.
Chromatographic system:
- A stainless steel column 15cmX4.6 mm, packed with octadecylsilane bonded to porous silica (5µm)
- Mobile phase: a mixture of 35 volumes of buffer solution prepared by dissolving 0.5gm each of sodium dihydrogen phosphate in 500ml of water, adjusted to pH 2.1 to 2.7 with O.P.A., and 65 volumes of acetonitrile
- Flow rate: 1ml per minute,
- Spectrophotometer set at 228nm,
- Injection volume: 50µl
Inject the reference solution and the test solution.
Calculate the content of Glimepiride.
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) Uniformity of content: Complies with the test stated under tablets.
For Glimepiride: Determine by liquid chromatography, as described under assay with the following modifications.
Test solution: Disperse 1 tablet in 20.0ml of solvent mixture with the aid of ultrasound and dilute to 25.0ml with the same solvent. Dilute further, if necessary with the solvent mixture.
Reference solution: Weigh accurately 10mg glimepiride reference standard in 10.0ml volumetric flask, shake to dissolve and dilute to volume with solvent mixture. Further dilute 1.0ml of this solution to 25.0ml with the same solvent. Dilute further, if necessary with the solvent mixture.
Inject the reference solution and test solution.
Calculate the content of glimepiride in the tablet.
11.0) Assay:
- For Metformin HCl: By UV spectroscopy
Test Solution: Weigh and powder 20 tablets. Disperse a quantity of the powder containing 50mg Metformin HCl in 70ml of water with the aid of ultrasound and dilute to 100.0ml with water. Dilute 1.0ml of this solution to 50.0ml with water.
Reference solution: A 0.001 per cent w/v solution of metformin HCl reference standard in water.
Measure the absorbance of the reference solution and the test solution at 232nm using water as blank. Calculate the content of metformin HCl in tablets.
- For Glimepiride: Determine b liquid chromatography.
Solvent mixture: A mixture of 90 volumes of acetonitrile and 10 volumes of water.
Test solution: Weigh and powder 20 tablets. Disperse a quantity of powder containing 1mg of glimepiride in 20ml of solvent mixture with aid of ultrasound and dilute to 25.0ml with the same solvent.
Reference solution: Weigh accuratel 10mg glimepiride reference standard in 10.0ml volumetric flask and dilute with solvent mixture. Transfer 1.0ml of this solution in a 25.0ml volumetric flask and dilute with solvent mixture.
Chromatographic system:
- A stainless steel column 15cmX4.6 mm, packed with octadecylsilane bonded to porous silica (5µm)
- Mobile phase: a mixture of 35 volumes of buffer solution prepared by dissolving 0.5gm each of sodium dihydrogen phosphate in 500ml of water, adjusted to pH 2.1 to 2.7 with O.P.A., and 65 volumes of acetonitrile
- Flow rate: 1ml per minute,
- Spectrophotometer set at 228nm,
- Injection volume: 20µl
Inject the reference solution and the test solution.
Calculate the content of Glimepiride in tablets.
Formula for calculation: For Metformin HCl
Abs. of test weight of STD 1 100 50 Potency
—————- X—————–X——-X——————X———X———X Average weight
Abs. of STD 100 50 Weight of test 1 100
Formula for calculation: For Glimepiride
Area of test weight of STD 1 25 Potency
—————- X—————–X——X——————X———X Average weight
Area of STD 10 25 Weight of test 100
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:
Wt.: Weight
mg: Miligram
ml: Milileter
STD: Standard
inHg: Inch of Mercury
rpm: Rounds per minute
CFU: Colony forming unit
Abs.: Absorbance
OPA: Orthophosphoric acid
HCl: Hydrochloride
