STP FOR FLUOXETINE 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 the contents of the tablets containing 10mg of fluoxetine with 10ml of methanol, centrifuge for 10 minutes and filter. Evaporate the filtrate to dryness with the aid of a current of air and mind heat. The residue complies with the following test.

Determine b infrared absorption spectrophotometry. Compare the spectrum with that obtained with fluoxetine HCl Reference standard or with the reference spectrum of fluoxetine HCl.

1. In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak 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 0.1 M HCl.

Time: 45 minutes

Speed: 50 rpm

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

Withdraw a suitable volume of the medium and filter.

Determine by liquid chromatography.

Diethylamine phosphate suspension: To 250ml of acetonitrile add 1ml of diethylamine, mix, and adjust the pH to 3.5 with O.P.A.

Note: Keep the suspension well-mixed.

Test solution: To 50ml of the filtrate obtained as given above, add 2ml of the diethylamine phosphate suspension and mix well.

Reference solution: Dissolve 0.022g of Fluoxetine HCl reference standard in sufficient 0.1 M HCl to produce 100ml and mix. Dilute 10ml of the solution to 100ml with 0.1 M HCl. To 5ml of the resulting solution, add 2ml of the diethylamine phosphate suspension and mix well.

Chromatographic system:

• A stainless steel column 15cmx4.6mm, packed with particles of silica the surface of which has been modified with chemically bonded cyano group (5µm),
• Mobile phase: a mixture of 0.4 volume of diethylamine, 40 volumes of acetonitrile and 60 volumes of water, adjusted to pH 3.5 with O.P.A.
• Flow rate: 2ml per minute
• Spectrophotometer set at 226nm,
• Injection volume: 50µl

Inject the reference solution. The test is not valid unless the relative standard deviation for replicate injections is not more than 2.0 per cent.

Inject the reference solution and the test solution.

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: Weigh and powder 20 tablets. Weigh a quantity of the powder containing 20mg of fluoxetine, disperse in 10ml of the mobile phase, mix and centrifuge.

Reference solution: A solution of Fluoxetine HCl reference standard containing the equivalent of 0.001 per cent w/v of Fluoxetine in the mobile phase.

Chromatographic system:

• A stainless steel column 15cmx4.6mm, packed with particles of silica the surface of which has been modified with chemically bonded cyano group (5µm),
• Mobile phase: a mixture of 35 volumes of acetonitrile and 65 volumes of a solution of triethlamine, prepared b adding to 10ml of triethlamine 980ml of water, mixing, adjusting the pH 6.0 with O.P.A. (about 4.5ml) and diluting 1000ml with water.
• Flow rate: 1ml per minute
• Spectrophotometer set at 215nm,
• Injection volume: 10µl

Inject the reference solution. The test is not valid unless the column efficiency is not less than 1100 theoretical plates and the tailing factor is not more than 2.0.

Inject the reference solution and the test solution. In the chromatogram obtained with the test solution, the area of any secondary peak is not more than the area of the peak in the chromatogram obtained with the reference solution (0.5 percent) and the sum of areas of all the secondary peaks is not more than twice the area of the peak in the chromatogram obtained with the reference solution (1.0 percent). Ignore any peaks with an area 0.1 times the area of the principal peak in the chromatogram obtained with the reference solution (0.05 percent).

10.0)    Assay: Determined by liquid chromatography.

Test solution: Weigh and powder 20 tablets. Weigh a quantity of the powder containing 20mg of Fluoxetine, disperse in 200ml of the mobile phase, mix and filter.

Reference solution: A 0.011 percent w/v solution of Fluoxetine HCl reference standard in the mobile phase.

Chromatographic system:

• A stainless steel column 25cmx4.0mm, packed with octadecylsilane bonded to porous silica (5µm)
• Mobile phase: a mixture of 33 volumes of a solution containing 0.3 per cent w/v G.A.A. and 0.64 per cent w/v of sodium pentanesulphonate, adjusted to pH 5.0 with 5M sodium hdroxide and 67 volumes of methanol,
• Flow rate: 1ml per minute
• Spectrophotometer set at 227nm,
• Injection volume: 10µl

Inject the reference solution. The test is not valid unless the relative standard deviation of replicate injections is not more than 2.0 per cent.

Inject the reference solution and the test solution.

Calculate the content of Fluoxetine in the tablets.

Alternative Method: By UV Spectrophotometer

Test Solution: Weigh and powder 20 tablets. Weight sample equivalent to 50mg of Fluoxetine 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 5ml of this solution to 25ml in 0.1 M HCl.

Reference Solution: Weigh 50mg of reference standard of Fluoxetine HCl 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 5ml of this solution to 25ml with 0.1 M HCl.

Check Absorbance of test as well as reference standard at about 264nm in UV Spectrophotometer.

Calculate the content of Fluoxetine in the tablets.

Formula:

Abs. of Test      STD Wt.(mg)   5             100               25      Potency

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

Abs. of STD        100              25      Test Wt.(mg)       5        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

G.A.A: Glacial acetic acid

HCl: Hydrochloric acid

O.P.A.: orthophosphoric acid