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.
Tablets were weighed individually and the percentage of deviation of its weight from the average weight was determined for each tablet. Formula for calculate the percentage of deviation = (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 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:
Apparatus: Paddle
Medium: 0.1 M hydrochloric acid; 900ml
Speed: 50 rpm
Time: 30 min
Withdraw a suitable volume of the medium and filter, discarding the first few ml of filtrate.
Determined by liquid chromatography
Solvent mixture: A mixture of equal volumes of acetonitrile and water.
Test solution: Dilute the filtrate if necessary, with the dissolution medium.
Reference Solution: Weigh about 5mg of ornidazole reference standard and 22 mg of ofloxacin reference standard into a 100ml of volumetric flask, add about 60ml of solvent mixture and sonicate to dissolve, make the volume up to the mark with solvent mixture and mix. Dilute 5.0ml of this solution to 50ml with the dissolution medium.
Chromatographic system:
- A stainless steel column 15cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µm), (such as Inertsil ODS-2)
- Mobile Phase: A mixture of 87 volumes of buffer solution prepared by dissolving 3.07g ammonium acetate and 5.38g sodium perchlorate in 1000ml of water, adjusted to pH 2.2 with O.P.A.
- Flow rate: 1ml per minute,
- Spectrophotometer set at 300nm,
- Injection volume: 10µl
Inject the reference solution. The test is not valid unless the column efficiency for both the analytes is not less than 2000 theoratical plates, the tailing factor is not more than 2.0 for ofloxacin peak and is not more than 2.5 for ornidazole peak and the relative standard deviation for replicate injections is not more than 5.0 per cent.
Inject the reference solution and the test solution. Run the chromatogram three times the etention time of ofloxacin peak. In the chromatogram obtained with test solution the area of any secondary peak due to ornidazole at relative retention
Calculate the content of ofloxacin and ornidazole released.
Limit: NLT 80% of the stated amount of ofloxacin and ornidazole.
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 substances: Determined by liquid chromatography.
Solvent mixture: A mixture of equal volumes of acetonitrile and water.
Test Solution: Disperse a quantity of the powdered tablets containing 200mg of ofloxacin into a 100ml volumetric flask add about 10ml 0.1M HCl and sonicate for 15 minutes with shaking and add 30ml of solvent mixture and sonicate for 60 minutes, after sonication cool to room temperature and make the volume up to the mark with solvent mixture and mix. Filter through 0.45nm filter. Dilute 5.0ml of this solution to 25.0 ml with solvent mixture.
Reference solution: Weigh and transfer about 50mg of ornidazole reference standard and 20 mg of ofloxacin reference standard into a 100ml volumetric flask. Add about 5.0ml 0.1 M HCl and 50ml of solvent mixture and sonicate to dissolve, make the volume upto the mark with solvent mixture and mix. Dilute 5ml of this solution to 50ml with the solvent mixture and mix. Further dilute 5.0ml this solution to 25.0ml with solvent mixture.
Chromatographic system:
- A stainless steel column 15cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µm)
- Mobile Phase: A mixture of 87 volumes of a buffer solution prepared by dissolving 3.07g m ammonium acetate and 5.38gm sodium perchlorate in 1000ml of water, adjusted to pH 4.0 with orthophosphoric acid and 13 volumes of acetonitrile
- Flow rate: 1ml per minute,
- Spectrophotometer set at 300nm,
- Injection volume: 10µl
Inject the reference solution. The test is not valid unless the column efficiency for both the analytes is not less than 2000 theoratical plates, the tailing factor is not less than 2.0 for ofloxacin peak and is not more than 2.5 for ornidazole peak and the relative standard deviation for replicate injections is not more than 5.0 per cent.
Inject the reference solution and the test solution. Run the chromatogram three time of ofloxacin peak. In the chromatogram obtained with test solution the area of any secondary peak due to ornidazole at relative retention time about 0.23 and 0.75 is not more than 0.5 times the area of the ornidazole peak in the chromatogram obtained with reference solution (0.5 per cent
) and sum of the areas of all the secondary peaks due to ornidazle is not more than the area of the ornidazole peak in the chromatogram obtained with reference solution (1.0 per cent). In the chromatogram obtained with the test solution, the area of any secondary peak is not more than the area of ofloxacin peak in the chromatogram obtained with reference solution (1.0 percent) and the sum of areas of all the secondary peaks is not more than twice the area for the ofloxacin peak in the chromatogram obtained with reference solution (2.0 percent). Ignore any peak with an area 0.05 times the area of the ofloxacin peak in the chromatogram obtained with reference solution (0.05percent).
11.0) Assay: Determined by liquid chromatography.
Solvent mixture: A mixture of equal volumes of acetonitrile and water.
Test solution: Weigh and powder 20 tablets. Transfer powder containing 200mg of ofloxacin into 100ml of volumetric flask. Add about 10ml of 0.1 M HCl and sonicate for 15 minutes with occasional shaking and add 30ml of solvent mixture and sonicate for 60 minutes, after sonication cool to room temperature and make the volume up to the mark with solvent mixture and mix. Filter through 0.45 mmfilter. Dilute 2.0ml of this solution to 200.0ml with solvent mixture.
Reference solution: Weigh and transfer accurately about 25mg of ofloxacin reference standard and 62.5mg of ornidazole reference standard into a 250ml volumetric flask. Add about 5.0ml of 0.1M HCl and 50.0ml of solvent mixture, sonicate to dissolve. Make the volume up to mark with solvent mixture and mix. Dilute 5.0ml of this solution to 25.0ml with solvent mixture.
Chromatographic system:
- A stainless steel column 15cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µm), (such as Inertsil ODS-2)
- Mobile Phase: A mixture of 87 volumes of a buffer solution prepared by dissolving 3.07g m ammonium acetate and 5.38gm sodium perchlorate in 1000ml of water, adjusted to pH 4.0 with orthophosphoric acid and 13 volumes of acetonitrile
- Flow rate: 1ml per minute,
- Spectrophotometer set at 300nm,
- Injection volume: 10µl
- Column temperature: 40°
Inject the reference solution. The test is not valid unless the column efficiency for both the principal peak is not less than 2000, 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 the reference solution and the test solution.
Calculate the content of ofloxacin and ornidazole in the tablets.
Formula for calculation:
Area of Test STD Wt.(mg) 5 100 200 Potency
—————–X————–X———X—————–X——X———–X Average weight
Area of STD 250 25 Test Wt.(mg) 2 100
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
HCl: Hydrochloric acid
O.P.A: Orthophosphoric acid
