## STP FOR DULOXETINE GASTRO-RESISTANT 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.

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%

4.0)      Identification Test:

In the assay, 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 in each of the basket and if the tablet has a soluble external coating, immerse the basket in water at room temperature for 5 minutes. Then operate the apparatus using simulated gastric fluid temperature maintained at 37±2° as the immersion fluid. After 2 hour of operation in simulated gastric fluid, lift the basket from the fluid, and observe the tablets. The tablets show no evidence of disintegration, cracking, or softening. Operate the apparatus, using simulated intestinal fluid temperature maintained at 37±2° as the immersion fluid, for the time specified in the monograph. Lift the basket from the fluid and observe the tablets. All of the tablets disintegrate 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:

1. Dissolution in Acid medium:

Medium: 0.1 M hydrochloric acid; 750ml

Speed: 100 rpm

Time: 120 min

Limit: NMT 10% of the stated amount of Duloxetine.

Withdraw a suitable volume of the medium, centrifuge at 3500 rpm for 15 minutes, use the supernatant liquid and measure the absorbance of the same, and suitably diluted with the dissolution medium, at the maximum at about 289nm. Calculate the content of Duloxetine in the medium from the absorbance obtained from a solution of known concentration of duloxetine HCl reference standard in 10ml methanol prepared with the aid of ultrasound and diluted to similar concentration using dissolution medium.

Calculate the content of Duloxetine in medium.

1. Dissolution in Buffer medium:

Medium: phosphate buffer pH 6.8; 1000ml

Speed: 100 rpm

Time: 60 min

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

Withdraw a suitable volume of the medium, centrifuge at 3500 rpm for 15 minutes, use the supernatant liquid and measure the absorbance of the same, and suitably diluted with the dissolution medium, at the maximum at about 289nm. Calculate the content of Duloxetine in the medium from the absorbance obtained from a solution of known concentration of duloxetine HCl reference standard in 10ml methanol prepared with the aid of ultrasound and diluted to similar concentration using dissolution medium.

Calculate the content of Duloxetine in medium.

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 up to 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)    Assay: Determined by liquid chromatography.

Test solution: Weigh and powder 20 tablets. Weigh a quantity of the powder containing 60mg of duloxetine, add 70ml of the mobile phase, mix with the aid of ultrasound and dilute to 100ml with the mobile phase. Dilute 5ml of this solution to 50 with the mobile phase.

Reference solution: A 0.0065 percent w/v solution of duloxetine HCl reference standard in mobile phase.

Chromatographic system:

• A stainless steel column 25cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µ),
• Mobile Phase: a mixture of 40 volumes of buffer solution prepared by dissolving 3.8 g of ammonium acetate in 1000ml water, adjusted to pH 5.7 with 10 percent w/v perchloric acid and 60 volumes of methanol,
• Flow rate: 1ml per minute,
• Spectrophotometer set at 240nm,
• Injection volume: 20µl

Inject reference solution. The test is not valid unless the column efficiency is not less than 2500 theoretical plates, the tailing factor is not more than 2.0 and the relative standard deviation for replicate injections is not more than 2.0 percent.

Inject reference solution and the test solution.

Calculate the content of Duloxetine in the tablet.

Alternative Method: By UV Spectrophotometer

Test Solution: Weigh and powder 20 tablets. Weight sample equivalent to 25mg of Duloxetine 100ml volumetric flask add 20ml methanol into it and sonicate to dissolve the test sample. Make up to mark with methanol. Filter and dilute 2ml of this solution to 25ml in 0.1 M HCl.

Reference Solution: Weigh 25mg of reference standard of Duloxetine HCl in 100ml of volumetric flask. Add 20ml methanol into it and sonicate to dissolve. Make up to mark with methanol. Dilute 2ml of this solution to 25ml with 0.1 M HCl.

Check Absorbance of test as well as reference standard at about 290nm in UV Spectrophotometer.

Calculate the content of Duloxetine in the tablets.

Formula:

Abs. of Test      STD Wt.(mg)  2            100               25      Potency

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

Abs. of STD        100              25     Test Wt.(mg)      2          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

Abs. Absorbance

w/v: Weight/Volume

HCl: Hydrochloric acid