QualityGuidances

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 peaks in the chromatogram obtained with the test solution corresponds to the principal peaks 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:

            Apparatus: Paddle

Medium: 900ml of phosphate buffer pH 6.8

            Speed: 100rpm

Time: 45 minutes

Limit: NLT 75% of the stated amount of Diclofenac sodium and Paracetamol.

Withdraw a suitable volume of the medium and filter.

Determine by liquid chromatography.

Test solution: Use the filtrate, dilute if necessary with the mobile phase.

Reference solution: A solution containing 0.0032 per cent w/v of paracetamol reference standard and 0.0005 per cent w/v of diclofenac sodium reference standard in the mobile phase.

            Chromatographic system:

• A stainless steel column 15cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µm).
• Mobile phase: a mixture of 25 volumes of water, 75 volumes of methanol and 1.0 volumes of G.A.A.
• Flow rate: 1.3ml per minute.
• Spectrophotometer set at 280nm,
• Injection volume: about 20µl

Inject the reference solution and the test solution.

Calculate the content of paracetamol and diclofenac sodium in the 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)    4-Aminophenol:

Solvent mixture A: Dissolve 4.6 g of tetrabutylammonium hydroxide (40 per cent) in 1000ml of methanol.

Solvent mixture B: A 0.05 M disodium hydrogen orthophosphate dedecahydrate solution.

Solvent mixture C: A 0.05 M sodium dihydrogen orthophosphate dehydrate solution.

Test solution: Weigh and powder 20 tablets. Weigh and transfer a quantity of powder containing 25mg of paracetamol to 25ml volumetric flask. Add 6.3ml of solvent mixture A, sonicate for 10 minutes and dilute to volume with a mixture of equal volumes of solvent mixture A and solvent mixture B.

Reference solution: A solution containing 0.00015 per cent w/v solution, each of 4-aminophenol reference standard and paracetamol reference standard in the mobile phase.

            Chromatographic system:

• A stainless steel column 25cm X4.6mm, packed with octylsilane bonded to porous silica (5µm).
• Mobile phase: a mixture of 325 volumes of solvent mixture A, 355 volumes of solvent mixture B and 340 volumes of solvent mixture C.
• Flow rate: 1.5ml per minute.
• Spectrophotometer set at 245nm,
• Injection volume: about 20µl

The relative retention times are 0.75 for the peaks due to 4-aminophenol and 1.0 for paracetamol.

Inject the reference solution. The test is not valid unless the resolution between the two principal peaks is not less than 2.0.

Inject the reference solution and the test solution. In the chromatogram obtained with the test solution, the area of any peak due to 4-aminophenol is not more than the area of the corresponding peak in the chromatogram obtained with reference solution (0.15 per cent).

11.0)    Assay: Determined by liquid chromatography.

Test solution: Weigh and powder 20 tablets. Weigh and transfer a quantity of the powder containing about 325 mg of paracetamol to a 50ml volumetric flask, add 30ml of mobile phase and disperse with the aid of ultrasound for about 10 minutes, cool and dilute to 50ml with the mobile phase, filter. Dilute 1ml of the filtrate to 50ml with the mobile phase.

Reference solution: A solution containing each of 0.013 per cent of paracetamol reference standard and 0.002 per cent of diclofenac sodium  reference standard in the mobile phase.

            Chromatographic system:

• A stainless steel column 15cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µm).
• Mobile phase: a mixture of 25 volumes of water, 75 volumes of methanol and 1.0 volumes of G.A.A.
• Flow rate: 1.3ml per minute.
• Spectrophotometer set at 280nm,
• Injection volume: about 20µl

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 reference solution and the test solution.

Calculate the content of Paracetamol and Diclofenac sodium in the tablets.

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

G.A.A.: glacial acetic acid

Abs. Absorbance

w/v: Weight/Volume