## STP FOR FINASTERIDE 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:

In the test for dissolution, the principal peak in the chromatogram obtained with the test solution corresponds to that 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:

Medium: 900ml of water

Time: 45 minutes

Speed: 50 rpm

Limit: NLT 80% of the stated amount of Finasteride.

Withdraw a suitable volume of the medium and filter.

Determine by liquid chromatography.

Test solution: The filtrate obtained as given above.

Reference solution: Dissolve a weighed quantity of finasteride reference standard in a mixture of 3 volumes of water and 7 volumes of acetonitrile and dilute with the same mixture to obtain a solution having a known concentration similar to the expected concentration of the test solution.

Chromatographic system:

• A stainless steel column 5.0cmX4.6mm packed with octadecylsilane bonded to porous silica (3µm),
• Mobile phase: a mixture of 42 volumes of water and 58 volumes of acetonitrile.
• Flow rate: 1.5ml per minute,
• Spectrophotometer set at 220nm,
• Injection volume: 200µl

Inject the reference solution. The test is not valid unless the tailing factor of the principal peak is not more than 2.0. Inject the reference solution and the test solution.    Calculate the content of Finasteride in tablets.

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: 50 volumes of acetonitrile and 50 volumes of water.

Test solution: Dissolve a quantity of powdered tablets containing 100mg of finasteride in 30ml of the solvent mixture and dilute to 50.0ml with the solvent mixture, centrifuge and filter the supernatant liquid.

Reference solution: Dilute 1.0ml of the test solution to 100.0ml with the solvent mixture.

Chromatographic system:

• A stainless steel column 25cmX4.0mm packed with octadecylsilane bonded to porous silica (5µm), (such as spherisorb ODS2),
• Mobile phase: a mixture of 10 volumes of acetonitrile, 10 volumes of tetrahydrofuran and 80 volumes of water,
• Flow rate: 1.5ml per minute,
• Spectrophotometer set at 210nm,
• Injection volume: 20µl
 Name Relative retention time Correction factor Finasteride impurity A1 0.9 2.4 Finasteride(Retention time about 28 minutes) 1.0 – Finasteride impurity B2 1.2 – Finasteride impurity C3 1.3 0.72

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.

Inject the reference solution and the test solution. Run the chromatogram twice the retention time of the principal peak. In the chromatogram obtained with the test solution the area of any peak corresponding to finasteride impurities A,B and C is not more than 0.3 times the area of the principal peak in the chromatogram obtained with the reference solution (0.3 per cent). The area of any other secondary peak is not more than 0.1 times the area of the principal peak in the chromatogram obtained with the reference solution (0.1 per cent) and the sum of the area of all other secondary peaks is not more than 0.6 times the area of the principal peak in the chromatogram obtained with the reference solution (0.6 per cent). Ignore any peak with an area less than 0.5 times the area of the principal peak in the chromatogram obtained with the reference solution (0.05 per cent).

11.0)    Uniformity of content:

(For tablets containing less than 10mg)

Determine by liquid chromatography

Test solution: Transfer one tablet to a suitable volumetric flask, add 5ml of a mixture of 3 volumes of water and 7 volumes of acetonitrile, disperse with the aid of ultrasound for 20 minutes. Dilute, as necessary with the solvent mixture with intermittent shaking to produce a solution containing 0.01 per cent w/v of finasteride, mix and filter.

Reference solution: A 0.01 per cent w/v solution of finasteride reference standard in a mixture of 3 volumes of water and 7 volumes of acetonitrile.

Chromatographic system:

• A stainless steel column 10cmX4.6mm packed with octadecylsilane bonded to porous silica (5µm),(such as hypersil ODS)
• Mobile phase: a mixture of equal volumes of acetonitrile and 0.0025 M of O.P.A.
• Flow rate: 1.5ml per minute,
• Spectrophotometer set at 240nm,
• Injection volume: 20µl

Calculate the content of Finasteride in tablets.

12.0)    Assay: Determined by liquid chromatography.

Test solution: Weigh and powder 20 tablets. Disperse a quantity of powder containing 50mg of Finasteride with 25ml of water. Add 350ml of a mixture of 3 volumes of water and 7 volumes of acetonitrile, mix with the aid of ultrasound for 30 minutes, dilute to 500ml with acetonitrile, centrifuge and filter the supernatant liquid.

Reference solution: A 0.01 per cent w/v solution of finasteride reference standard in a mixture of 3 volumes of water and 7 volumes of acetonitrile.

Chromatographic system:

• A stainless steel column 10cmX4.6mm packed with octadecylsilane bonded to porous silica (5µm),(such as hypersil ODS)
• Mobile phase: a mixture of equal volumes of acetonitrile and 0.0025 M of O.P.A.
• Flow rate: 1.5ml per minute,
• Spectrophotometer set at 240nm,
• Injection volume: 20µl

Inject reference solution. The test is not valid unless the tailing factor of the principal peak is less than 2.0 and the relative standard deviation for replicate injection is not more than 2.0

Inject the reference solution and the test solution.

Calculate the content of Finasteride in tablets.

Formula:

Area of Test      STD Wt.(mg)            500                   Potency

—————–X——————-X———————X———–X Average wt.

Area of STD        100                    Test Wt.(mg)           100

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

O.P.A: Orthophosphoric acid

w/v: Weight/Volume