## STP FOR FLUVOXAMINE TABLETS

• Description: Visual
• 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
• 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%
• Identification Test:
1. Shake a quantity of powdered tablets containing 50mg of Fluvoxamine maleate with 10ml of acetonitrile for 10 minutes, centrifuge and evaporate the supernatant liquid to dryness. On the residue, determined by infrared absorption spectrophotometry. Compare the spectrum obtained with Fluvoxamine maleate reference standard or with the reference spectrum of Fluvoxamine maleate.
2. Determine b thin-layer chromatography, coating the plate with silica gel; HF254.

Mobile phase: A mixture of 5 volumes of 13.5 M ammonia and 95 volumes of ethanol (95 per cent)

Test solution: Shake a quantity of the powdered tablets containing 50mg of Fluvoxamine maleate with 5ml of methanol for 10 minutes, centrifuge and use the supernatant liquid.

Reference solution: A 1.0 per cent w/v solution of Fluvoxamine maleate reference standard in methanol.

Apply to the plate 5µl of each solution. Allow the mobile phase to rise 15cm. Dry the plate in air and examine under ultraviolet light at 254nm. The two principal spots in the chromatogram obtained with the test solution correspond to that in the chromatogram obtained with the reference solution.

5.0)      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.

6.0)      Dimension of Tablet:

Length, breadth and thickness are determined by vernier in mm.

7.0)      Dissolution:

Medium: 900ml of water

Time: 20 minutes

Speed: 50 rpm

Limit: NLT 75% of the stated amount of Fluvoxaime.

Withdraw a suitable volume of the medium and centrifuge. Measure the absorbance of the clear centrifuge liquid, suitably diluted if necessary with dissolution medium at 244nm. Calculate the content of Fluvoxamine maleate, in the medium taking 270 as the specific absorbance at 244nm.

8.0)      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.

9.0)      Related substance: Determined by liquid chromatography.

Test solution: Disperse a quantity of powdered tablets containing 0.25 g of fluvoxamine maleate with 125ml of the mobile phase for 10 minutes and dilute to 250ml with the mobile phase. Centrifuge and use the supernatant liquid.

Reference solution (a): Dilute 1ml of the test solution to 100ml with the mobile phase.

Reference solution (b): Add 1ml of 1M HCl to 10ml of the test solution and heat on a water bath for 10 minutes.

Chromatographic system:

• A stainless steel column 25cmx4.6mm, packed with endcapped octylsilane bonded to porous silica (5µm),
• Column temperature: 35°
• Mobile phase: a mixture of 40 volumes of a solution containing 1.25 per cent w/v of diammonium hydrogen orthophosphate and 0.275 per cent w/v of sodium heptanesulphonate monohydrate and 60 volumes of methanol. Adjusting the pH to 3.5 with O.P.A.
• Flow rate: 2ml per minute
• Spectrophotometer set at 254nm,
• Injection volume: 20µl

Inject reference solution (b).The relative retention time with reference to Fluvoxamine maleate (retention time: about 7 to 9 minutes) for addition product is about 0.65.

Inject the reference solution (a). 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 reference solution (a) and the test solution. In the chromatogram obtained with the test solution, the area of any peak due to ‘addition product’ is not more than 3 times the area of the principal peak in the chromatogram obtained with reference solution (a) (3.0 per cent). The area of any other secondary peak is not more than 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.5 per cent). Ignore the peak due to maleic acid which elutes immediately after the solvent front and any peak with a area less than 0.05 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent).

10.0)    Assay: Determined by liquid chromatography.

Test solution: Weigh and powder 20 tablets. Disperse a quantity of the powder containing 0.25g of Fluvoxamine maleate with 125 ml of the mobile phase for 10 minutes and dilute to 250ml with the mobile phase, centrifuge. Dilute 1ml of the supernatant liquid ton 10ml with mobile phase.

Reference solution: A 0.01 percent w/v solution of Fluvoxamine maleate reference standard in the mobile phase.

Chromatographic system:

• A stainless steel column 25cmx4.6mm, packed with endcapped octylsilane bonded to porous silica (5µm),
• Column temperature: 35°
• Mobile phase: a mixture of 40 volumes of a solution containing 1.25 per cent w/v of diammonium hydrogen orthophosphate and 0.275 per cent w/v of sodium heptanesulphonate monohydrate and 60 volumes of methanol. Adjusting the pH to 3.5 with O.P.A.
• Flow rate: 2ml per minute
• Spectrophotometer set at 254nm,
• Injection volume: 20µl

Inject the reference solution and the test solution.

Calculate the content of Fluvoxamine maleate in the tablets.

Alternative Method: By UV Spectrophotometer

Test Solution: Weigh and powder 20 tablets. Weight sample equivalent to 50mg of Fluvoxamine maleate 100ml volumetric flask add 20ml 0.1 M HCl into it and sonicate to dissolve the test sample. Make up to mark with 0.1 M HCl. Filter and dilute 1ml of this solution to 50ml in 0.1 M HCl.

Reference Solution: Weigh 50mg of reference standard of Fluvoxamine maleate in 100ml of volumetric flask. Add 20ml 0.1 M HCl into it and sonicate to dissolve. Make up to mark with 0.1 M HCl. Dilute 1ml of this solution to 50ml with 0.1 M HCl.

Check Absorbance of test as well as reference standard at about 254nm in UV Spectrophotometer.

Calculate the content of Fluvoxamine maleate in the tablets.

Formula:

Abs. of Test      STD Wt.(mg)   1             100              50      Potency

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

Abs. of STD        100              50      Test Wt.(mg)       1        100

Acceptance criteria: 92.5%-105.0%

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

G.A.A: Glacial acetic acid

HCl: Hydrochloric acid

O.P.A.: orthophosphoric acid