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:
- Shake a quantity of the powdered tablets containing 0.1g of Phenytoin sodium with 20ml of water, filter, acidify with dilute HCl and extract with 10ml of chloroform. Wash the chloroform extract with water, dry with anhydrous sodium sulphate and evaporate to dryness and dry the residue at 105°. The residue complies with the following test.
Determine b infrared absorption spectrophoyometry. Compare the spectrum with that obtained with phenytoin sodium reference standard treated in the same manner or with the reference spectrum of Phenytoin.
- Triturate a quantity of the powdered tablets containing 0.5 g of Phenytoin sodium with 10ml of water and filter. Acidify with dilute HCl; a white precipitate is produced.
- The powdered tablets, when moistened with HCl and introduced on a platinum wire into a flame, impart a yellow color to the flame.
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) 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.
9.0) Related substances:
Determine by thin-layer chromatography, coating the plate with silica gel GF254.
Mobile phase: A mixture of 75 volumes of hexane and 30 volumes of dioxan.
Test solution: Shake a quantity of the powdered tablets containing 0.1 g of Phenytoin sodium with 5ml of methanol, warm on a water- bath with shaking and filter.
Reference solution: A 0.01 per cent w/v solution of benzophenone in methanol.
Apply to the plate 5µl of each solution. Allow the mobile phase to rise 12cm. Dry the plate in air and examine under ultraviolet light at 254nm. In the chromatogram obtained with the test solution any spot corresponding to benzophenone is not more intense than the spot in the chromatogram obtained with the reference solution.
10.0) Assay:
Weigh and powder 20 tablets. Weigh a quantity of the powder containing about 0.25g of Phenytoin sodium, shake with 40ml of 0.01 M sodium hydroxide for 5 minutes and add sufficient 0.01 M sodium hydroxide to produce 50ml. Centrifuge, acidify 25ml of the clear liquid with 10ml of 0.1 M HCl and extract successively with 50, 40, 25 and 25ml of ether. Wash the combined extracts with 10ml of water, evaporate to dryness and dry the residue at 105°. Dissolve in 50ml of anhydrous pyridine and titrate with 0.1 M tetrabutylammonium hydroxide, using 0.3 per cent w/v solution of thymol blue in pyridine as indicator and taking care to prevent absorption of carbon dioxide from the atmosphere. Carry out a blank titration.
1ml of 0.1 M tetrabutylammonium hydroxide is equivalent to 0.02743 g of Phenytoin sodium.
Alternative method (By liquid chromatography).
Test solution (a): Weigh a quantity of the powdered tablets containing 50mg of Phenytoin sodium add 15ml mobile phase, mix with the aid of ultrasound for 15 minutes and dilute to 100ml with mobile phase. Filter and dilute 2ml to 25ml in mobile phase.
Reference solution: Dissolve 50mg of Phenytoin sodium reference standard in mobile phase in 100ml volumetric flask. Dilute 2ml to 25ml with mobile phase.
Chromatographic system:
- A stainless steel column 15cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µm).
- Mobile phase: a mixture of 400 volumes of buffer prepared by dissolving 3.5g of KH2PO4 in 500ml water adjusted to pH 2.8 with O.P.A. and 600 volumes of methanol.
- Flow rate: 1.2ml per minute.
- Spectrophotometer set at 220nm,
- Injection volume: about 20µl
Inject the test solution and reference solution . Calculate the contemt of Phenytoin sodium in the tablets.
Formula for calculation:
Area of TEST STD wt. (mg) 2 100 25 Potency
———————X——————–X———X————–X———X———–X Avg. Wt.
Area of STD 100 25 Test wt (mg) 2 100
Acceptance criteria: 90.0%-110.0%
11.0) 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
O.P.A.: Orthophosphoric acid
w/v: Weight/volume
HCl: Hydrochloric acid
