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 peak in the chromatogram obtained with the test solution corresponds to the peak 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 0.1 M HCl

Speed: 50rpm

Time: 45 minutes

            Limit: NLT 80% of the labeled amount of Donepezil is dissolved.

            Withdraw a suitable volume of the medium and filter

Determine by liquid chromatography

Test solution: Dilute the filtrate, if necessary, with the dissolution medium.

Reference solution: Dissolve a weighed quantity of donepezil reference standard in the dissolution medium, dilute to obtain a                 solution having a known concentration similar to expected concentration of the test solution.

            Chromatographic system:

• A stainless steel column 25cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µ),
• Column Temperature: 40°
• Mobile Phase: a mixture of 60 volumes of buffer pH 2.2 prepared by dissolving about 6.8 g of potassium dihydrogen phosphate in 1000ml of water. Add 5ml of triethylamine and adjust the pH to 2.2 with O.P.A., filter and 40 volumes of methanol.
• Flow rate: 1.2ml per minute,
• Spectrophotometer set at 268nm,
• Injection volume: 50µl

Inject the reference solution and the test solution.

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)    Related substances: Determine by liquid chromatography.

            Solvent mixture: 25 volumes of acetonitrile and 75 volumes of water.

            Test solution: Weigh a quantity of powdered tablets containing about 50mg of donepezil HCl, add 25ml of solvent mixture,                         sonicate for 15 minutes and make up the volume to 50ml with solvent mixture and filter.     

            Reference solution (a): A 0.08 per cent w/v solution of Ivermectin reference standard in methanol.

            Reference solution (a): A 0.1 per cent w/v solution of donepezil HCl reference standard in solvent mixture.

Reference solution (b): Dilute 1ml of reference solution (a) to 100ml with solvent mixture.

            Chromatography System:

• A stainless steel column 25cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µm),
• Column temperature: 50°
• Mobile Phase: A: a buffer solution pH 6.5 prepared by adding 1ml of O.P.A in 1000ml of water, adjust the pH to 6.5 with triethylamine and filter,

1. acetonitrile

• Flow rate: 1.5ml per minute,
• A gradient programme using the conditions given below,
• Spectrophotometer set at 286nm,
• Injection volume: 20µl

Inject reference solutions (b). The test is not valid unless the column efficiency is not less than 20000 theoretical plates and the tailing factor is not more than 2.0.

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 1.5 times the area of the peak in the chromatogram obtained with reference solution (b) (1.5 per cent) and 3 times the area of the peak in the chromatogram obtained with the reference solution (b) (3.0 per cent).

11.0)    Assay: Determined by liquid chromatography.

Test solution: Transfer intact tablets and sonicate to disperse the tablets completely, add mobile phase and sonicate again for 30 minutes and cool and make up the volume with mobile phase. Allow the excipients to settle down completely and dilute finally with mobile phase to obtain a solution of final concentration of 0.01 per cent w/v and filter.

Reference solution: A 0.001 per cent w/v solution of Donepezil HCl reference standard in mobile phase.

            Chromatographic system:

• A stainless steel column 25cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µ),
• Column Temperature: 40°
• Mobile Phase: a mixture of 60 volumes of buffer pH 2.2 prepared by dissolving about 6.8 g of potassium dihydrogen phosphate in 1000ml of water. Add 5ml of triethylamine and adjust the pH to 2.2 with O.P.A., filter and 40 volumes of methanol.
• Flow rate: 1.2ml per minute,
• Spectrophotometer set at 268nm,
• Injection volume: 20µl

Inject reference solution. The test is not valid unless the column efficiency is not less than 7000 theoretical plates.The tailing factor is not more than 1.5. 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 Donepezil the tablet.

Alternative Method: By UV Spectrophotometer

Test Solution: Weigh and powder 20 tablets. Weight sample equivalent to 25mg of Donepezil 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 25ml in 0.1 M HCl.

Reference Solution: Weigh 25mg of reference standard of Donepezil 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 25ml with 0.1 M HCl.

Check Absorbance of test as well as reference standard at about 316nm in UV Spectrophotometer.

Calculate the content of Donepezil in the tablets.

  Formula:

Abs. of Test      STD Wt.(mg)  1            100               25      Potency

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

Abs. of STD        100              25     Test Wt.(mg)      1           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

O.P.A.: Orthophosphoric acid