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:
Method A
Apparatus: Paddle
Medium: 0.1 M hydrochloric acid; 750ml
Speed: 75 rpm
Time: 120 minutes
Limit: NMT 15% of the stated amount of Esomeprazole.
At the end of 120 minutes, drain the acid solution slowly without losing any tablet fragments. Transfer the entire content to a 100ml volumetric flask (in the case of 20mg tablets) or a 200ml volumetric flask (in case of 40mg tablets), add about 80ml of methanol (in case of 20mg tablets) or 160ml (in case of 40mg tablets) and disperse the tablets with the aid of ultrasound for 15 minutes. Dilute to volume with methanol. Mix well with the aid of ultrasound to disperse the tablets further for 5 minutes and centrifuge at 4000 rpm for 10 minutes. Dilute 5ml of the supernatant liquid to 25ml with the mobile phase.
Using the resulting solution as the test solution, carry out the determination as described in the assay. Calculate the content of Esomeprazole in the supernatant liquid. Calculate the percentage of esomeprazole released in the acid medium by subtracting the content of Esomeprazole in the test solution from the total content determined in the assay.
Method B
Apparatus: Paddle
Medium: phosphate buffer pH 6.8; 900ml
Speed: 75 rpm
Time: 60 min
Limit: NLT 75% of the stated amount of Esomeprazole.
Transfer another 6 tablets and run the apparatus for 120 minutes in 0.1 M HCl. Decant the medium without losing the tablet and add phosphate buffer pH 6.8 and run the apparatus for 60 minutes. Using the supernatant liquid as the test solution, carry out the determination as described in the assay. Calculate the content of Esomeprazole 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) Assay: Determined by liquid chromatography.
Test solution: Weigh and powder 20 tablets. Weigh a quantity of the powder containing 0.24g of esomeprazole, add about 150ml of methanol and mix with the aid of ultrasound for 15 minutes. Mix and add sufficient methanol to produce 250ml. Mix with the aid of ultrasound for a further 5 minutes and centrifuge. Dilute 5ml of the clear supernatant liquid to 25ml with the mobile phase.
Reference solution: Weigh 0.055g of Esomperazole magnesium reference standard dissolved in 50ml of methanol, add sufficient mobile phase to produce 250ml and mix well.
Chromatographic system:
- A stainless steel column 25cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µ),
- Mobile Phase: a mixture of equal volumes of methanol and a buffer solution prepared by dissolving 6.8g of potassium dihydrogen phosphate and about 1g of sodium hydroxide in 1000ml of water, and adjusting pH to 7.0 with O.P.A.
- Flow rate: 1.5ml per minute,
- Spectrophotometer set at 300nm,
- Injection volume: 50µl
Inject reference solution. The test is not valid unless the column efficiency is not less than 5000 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 ESomeprazole in the tablet.
Alternative Method: By UV Spectrophotometer
Test Solution: Weigh and powder 20 tablets. Weight sample equivalent to 40mg of Esomeprazole 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 40mg of reference standard of Esomeprazole magnesium 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 280nm in UV Spectrophotometer.
Calculate the content of Esomeprazole 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
