## STP FOR METFORMIN HYDROCHLORIDE TABLETS

1.0)   Description: Visual

2.0) Average Weight: Check weight of 20 tablets at randomly and calculate the average weight by formula :                                                             weight  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:

1. Shake a quantity of the powdered tablets containing 20mg of Metformin Hydrochloride with 20ml of ethanol, filter, evaporate the filtration to dryness on a water bath and dry the residue at 105° for 1 hour.

On residue, determine by infrared absorption spectroscopy. Compare the spectrum with that obtained with metformin hydrochloride reference standard or with the reference spectrum of metformin hydrochloride.

1. Triturate a quantity of the powdered tablets containing 50mg of metformin hydrochloride with 10ml of water and filter. To 5ml of the filtrate, add 1.5ml of 5 M sodium hydroxide, 1ml of 1-napthol solution and, dropwise with shaking, 0.5ml of sodium hypochlorite solution (3 per cent); an orange red color is produced which darkens on keeping.
2. The filtrate obtained in test B gives reaction (A) of chlorides.

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.  If obviously cracked, chipped or broken tablets are present in the sample                            after tumbling, the sample fails the test.

9.0)      Dissolution:

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: 45 minutes

Speed: 100 rpm

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.

Limit: NLT 75% of the stated amount of Metformin HCl.

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 substance:

Determined by liquid chromatography.

Test solution: Shake a quantity of the powdered tablets containing 0.5gm of metformin hydrochloride with 100ml of water and filter.

Reference solution (a): Dilute 0.1ml of the test solution to 100ml with water.

Reference solution (b): A 0.0001 per cent w/v solution of dicyandiamide in water.

Chromatographic system:

• A stainless steel column 30cmX4 mm, packed with octadecylsilane bonded to porous silica (10µm)
• Mobile phase: a solution containing 0.087 per cent w/v of sodium pentanesulphonate and 0.12 per cent w/v of sodium chloride, adjust to pH 3.5 using 1 per cent v/v solution of O.P.A.
• Flow rate: 1ml per minute,
• Spectrophotometer set at 218nm,
• Injection volume: 20µl

Inject reference solution (a), (b) and the test solution. Run the chromatogram 3 times the retention time of the principal peak. In the chromatogram obtained with the test solution, the area of any peak corresponding to dicyandiamide is not more than the area of the peak in the chromatogram obtained with reference solution (b) (0.02 per cent). The area of any other secondary peak is not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.1 per cent).

12.0)    Assay:

Determined by UV spectroscopy.

Weigh and powder 20 tablets. Weigh a quantity of the powder containing about 0.1gm of Metformin HCl, shake with 70ml of water for 15 minutes, dilute to 100.0ml with water and filter. Dilute 10.0ml of the filtrate to 100.0ml with water. Further dilute 10.0ml to 100.0ml with water and measure the absorbance of the resulting solution at the maximum at about 232nm. Calculate the content of Metformin HCl taking 798 as the specific absorbance at 232nm.

Formula for calculation:

Abs. of test          1000           100                    100          100

—————- X————-X——————-X———X———-XAverage weight

798                   100           Weight of test      10            10

Acceptance criteria: 95.0%-105.0%

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: Hydrochloride

OPA: Orthophosphoric acid

Abs.: Absorbance