## STP FOR DIACEREIN CAPSULES

• Description: Visual
• Average Weight: Check weight of 20 Capsules at randomly and calculate the average weight by formula :  wt of 20 tablets (gm) x 1000 / 20. found avg. wt in mg
• Average Fill: Check weight of 20 Capsules at randomly. And calculate the average weight by above formula and subtract empty weight of capsule from average weight.
• Uniformity of weight:

Weigh 20 capsules 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.

Capsules were weighed individually and the percentage of deviation of its weight from the average weight was determined for each capsule. Formula for calculate the percentage of deviation = (experimental weight – theoretical weight)    x 100%

Theoretical weight

 Average weight of capsules Percentage deviation 300 mg or less 10.0 % More than 300 mg 7.5%
• Identification Test:

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.

6.0)      Disintegration Time

Unless otherwise stated in the individual monograph, introduce one capsule 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 capsules fail to disintegrate, repeat the test on 12 additional capsules; not less than 16 of the total of 18 capsules tested disintegrate.

If the capsules 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 capsules in the repeat test disintegrate.

7.0)      Dimension of Capsule:

Length and diameter are determined by vernier in mm

8.0)      Dissolution:

Apparatus: Paddle

Medium: 900ml of citrate buffer pH 6.0 prepared by dissolving 1.816g of citric acid and 11.91 g of trisodium citrate in 1000ml of water adjusted to pH 6.0 with 0.1 M sodium hydroxide or 0.1 M HCl.

Time: 45 minutes

Speed: 75 rpm

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

Withdraw a suitable volume of the medium and filter. Measure the absorbance of the filtrate, suitably dilutes if necessary with dissolution medium at 340nm.Calculate the content of diacerein in the medium from the absorbance obtained from a solution prepared by dissolving 25mg of diacerein reference standard in 10.0ml of acetonitrile and dilute to 100ml with dissolution medium. Dilute 5ml of this solution to 50ml with the dissolution 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 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.

Note: store and inject the solutions at 4°.

Solvent mixture (a): 60 volumes of acetonitrile and 20 volumes of water.

Solvent mixture (b): 20 volumes volumes of tetrahydrofuran, 60 volumes of acetonitrile and 20 volumes of water.

Test solution: Disperse the contents of capsules containing about 25mg of Diacerein in 10ml of tetrahydrofuran, sonicate and dilute to 50ml with solvent mixture (a), filter.

Reference solution (a): Dissolve about 25mg of the diacerein reference standard in 10ml of tetrahydrofuran, sonicate and dilute to 50ml with solvent mixture (a).

Reference solution (b): Dilute 5ml of reference solution (a) to 50ml with solvent mixture (b). Further dilute 5ml of this solution to 50ml with the same solvent.

Chromatographic system:

• A stainless steel column 25cmx4.6mm, packed with octadecylsilane bonded to porous silica (3.5µm) (such as waters X-terra RP 18).
• Mobile phase: a mixture of 62 volumes of a buffer solution prepared by diluting 2ml of orthophosphoric acid in 1000ml of water and 38 volumes of acetonitrile.
• Flow rate: 1ml per minute
• Spectrophotometer set at 254nm,
• Injection volume: 10µl

Inject the reference solution (b). The test is not valid unless the relative standard deviation for replicate injections is not more than 5.0 per cent.

Inject reference solution (b) 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 principal peak in the chromatogram obtained with reference solution (b) (1.0 per cent) and the sum of areas of all the secondary peaks is not more than 2.0 times the area of the principal peak in the chromatogram obtained with reference solution (b) (2.0 per cent).

11.0)    Assay: Determined by liquid chromatography.

Solvent mixture: 50 volumes of buffer pH 3.0 prepared by diluting 1.4ml of triethylamine in 100ml of water, adjusted to ph 3.0 with O.P.A. and 50 volumes of acetonitrile.

Test solution: Disperse the contents of capsules containing about 50mg of Diacerein in 200ml of solvent mixture, sonicate for 10 minutes and dilute to 250ml with the solvent mixture, filter. Further dilute 5ml of this solution to 20ml with the solvent mixture.

Reference solution: A 0.005 per cent w/v solution of diacerein reference standard in the solvent mixture.

Chromatographic system:

• A stainless steel column 15cmx4.6mm, packed with octadecylsilane bonded to porous silica (3.5µm)
• Mobile phase: a mixture of 75 volumes of a buffer solution prepared by diluting 1.4ml of triethylamine in 100ml of water adjusted to pH 7.0 with O.P.A. 25 volumes of acetonitrile.
• Flow rate: 1ml per minute
• Spectrophotometer set at 254nm,
• Injection volume: 20µl

Inject the reference solution. The test is not valid unless the theoretical plate is not less than 2000, tailing factor is not more than 2.0 and 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 Diacerein in the capsules.

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: Hydrochloric acid

w/v: Weight/volume