STP FOR METFORMIN HYDROCHLORIDE PROLONGED RELEASE TABLETS

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:

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)      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 6.5 g. 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.

8.0)      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: 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.

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 substance:

Determined by liquid chromatography.

Solvent mixture: A 2.5 per cent of v/v solution of acetonitrile in water.

Test solution: Disperse a quantity of the powdered tablets containing about 0.5gm of Metformin HCl in 100ml of the solvent mixture. Take 10ml of this solution and centrifuge at 3500rpm for 15 minutes. Dilute 5ml of this supernatant to 100ml with the solvent mixture.

Reference solution (a): A 0.0005 per cent w/v solution of dicyandiamide in the solvent mixture.

Reference solution (b): A 0.0025 per cent w/v solution of metformin HCl reference standard in the solvent mixture.

Reference solution (c): Dilute 1ml of each of reference solution (a) and reference solution (b), to 100ml with the solvent mixture.

Chromatographic system:

• A stainless steel column 25cmX4.6 mm, packed with octadecylsilane bonded to porous silica (5µm)
• Mobile phase: a mixture of 90 volumes of buffer solution prepared by dissolving 1gm each of sodium heptanes sulphonate and sodium chloride to 1800ml of water, adjusted to pH 3.85 with 0.06M O.P.A. and dilute to 2000ml with water and 10 volumes of acetonitrile.
• Flow rate: 1ml per minute,
• Spectrophotometer set at 218nm,
• Injection volume: 20µl

Inject reference solution (c). The test is not valid unless the tailing factor of the peak due to metformin hydrochloride is not more than 2.0. The resolution between the peaks due to dicyandiamide and metformin HCl is not less than 2.0. The relative standard deviation for replicate injections is not more than 2.0 per cent for metformin HCl and not more than 10 per cent for dicyandiamide.

Inject reference solution (c) and the test solution. In the chromatogram obtained with the test solution the area of peak corresponding to dicyandimide is not more than the area of the peak due to dicyandimide in the chromatogram obtained with reference solution (c) (0.02 per cent) and the area of any other secondary peak is not more than the area of peak due to metformin HCl in the chromatogram obtained with reference solution (c) (0.1 per cent).

11.0)    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 ml of the filtrate to 100 ml with water. Further dilute 10 ml to 100 ml 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:

Area of test          1000                  100                        100             100

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

798                   100              Weight of test               10               10

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

HCl: Hydrochloride

O.P.A.: Orthophosphoric acid