1.0) Description: Visual
2.0) Average filled volume: Not less than labeled claim.
Take 10 bottles and measure the volumes of separately each all bottle with calibrated or certified volumetric flask.
3.0) Uniformity of Volume: Randomly pick up sample and check its Average volume.
The average net volume of the contents of the containers is not less than the labeled amount, and the net volume of the contents of any single containers is not less than 91 per cent and not more than 109 per cent of the labeled amount where the labeled amount is 50ml or less, or not less than 95.5 per cent and not more than 104.5 per cent of the labeled amount where the labeled amount is more than 650ml but not more than 200ml, or not less than 97 per cent but not more than 103 per cent of the labeled amount where the labeled amount is more than 200ml but not more than 300ml.
If this requirement is not met, determined the net volume of the contents of 10 additional containers. The average net volume of the contents of the 20 containers is not less than the labeled amount, and the net volume of the content of not more than 1 of 20 containers is less than 91 per cent or more than 109 per cent of the labeled amount where the labeled amount is 50ml or less, or not less than 95.5 per cent and not more than 104.5 per cent of the labeled amount where the labeled amount is more than 50ml but not more than 200ml, or not less than 97 per cent but not more than 103 per cent of the labeled amount where the labeled amount is more than 200ml but not more than 300ml. None of individual weights deviated by more than twice that of respective minimum and maximum percentage limits.
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.
Detemine by thin-layer chromatography, coating the plate with silica gel G.
Solvent mixture: 1volume of dichloromethane and 1 volumes of methanol.
Mobile phase: A mixture of 1 volume of 13.5 M ammonia 24 volumes of ethanol and 75 volumes of toluene.
Test solution: Disperse a quantity of the oral solution containing 50 mg of Hydroxyzine HCl with 5 ml of solvent mixture and dilute to 50 ml with the solvent mixture, centrifuge and use the supernatant liquid.
Reference solution (a): A 1.0 per cent w/v solution of Hydroxyzine HCl reference standard in the solvent mixture.
Reference solution (b): A solution containing 0.5 per cent w/v each of Hydroxyzine HCl reference standard and meclozine HCl reference standard in the solvent mixture.
Apply to the plate 30 µl of the test solution and 2 µl of reference solution (a) and (b). Allow the mobile phase to rise 15 cm. Dry the plate in air, spray with potassium iodobismuthate solution, heat at 110° for 5 minutes and allow to cool. The principal spot in the chromatogram obtained with the test solution corresponds to that in the chromatogram obtained with reference solution (a). The test is not valid unless the chromatogram obtained with reference solution (b) shows two clearly separated spots.
5.0) pH: 2.7 to 3.0
6.0) Leak test:
The apparatus is used to test for the integrity of packed strips, blisters and Alu-Alu Blister pack containing tablets and syrup bottles. 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 bottles for any leakage by opening the bottles manually. If anyone bottle shows evidence of leakage, reject the sample, stop the machine and immediately take corrective action.
7.0) Related substances: Determined by liquid chromatography.
Test solution: Disperse a quantity of the oral solution containing 50 mg of Hydroxyzine HCl with 10 ml of mobile phase and dilute to 50 ml with the mobile phase.
Reference solution (a): Dilute 2 ml of the test solution to 100 ml with the mobile phase. Further dilute 1 ml of this solution to 10 ml with mobile phase. Reference solution (b): Dilute 1ml of reference solution (a) to 10ml with mobile phase A.
Reference solution (b): A 0.01 per cent w/v solution of Hydroxyzine HCl reference standard in the mobile phase.
Reference solution (c): Dilute 1 ml of the test solution to 10 ml with the mobile phase, further dilute 1 ml of this solution to 20 ml with the mobile phase.
Chromatographic system:
- A stainless steel column 15 cm X 4.6 mm, packed with octadecylsilane bonded to porous silica (5 µm).
- Mobile phase: a mixture of 14 volumes of triethylamine, 300 volumes of acetonitrile and 686 volumes of a 0.075 per cent w/v solution of sodium methanesulphonate, adjusting pH 2.7 with sulphuric acid,
- Flow rate: 1 ml per minute.
- Spectrophotometer set at 230 nm,
- Injection volume: about 20 µl
The retention time of Hydroxyzine is about 9 minutes.
Inject reference solution (b). The test is not valid unless the peak –to-valley ratio is not less than 10, where Hp is the height above the baseline of the peak immediately before the peak due to Hydroxyzine and Hv is the height above the baseline of the lowest point of the curve separating this peak from the peak due to Hydroxyzine.
Inject reference solution (a), (c) and the test solution. Run the chromatogram 3 times the retention time of the principal peak. In the chromatogram obtained with the test solution, the area of any secondary peak is not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.2 per cent). The sum of the areas of all the secondary peaks is not more than 2.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.5 per cent). Ignore any peak with an area less than the area of the principal peak in the chromatogram obtained with reference solution (c) (0.5 per cent).
8.0) Assay: Determined by liquid chromatography.
Test solution: Disperse a quantity of the oral solution containing 50 mg of Hydroxyzine HCl with 10 ml of water for 20 minutes, add 125 ml of methanol and shake for a further 30 minutes and dilute to 250 ml with 30 per cent v/v solution of acetonitrile, filter. Dilute 5 ml of this solution to 10 ml with a 30 per cent v/v solution of acetonitrile.
Reference solution (a): A 0.01 per cent w/v solution of Hydroxyzine HCl reference standard in 30 per cent of acetonitrile.
Reference solution (b): A 0.01 per cent w/v solution of Hydroxyzine hydrochloride reference standard in the mobile phase.
Chromatographic system:
- A stainless steel column 15 cm X 4.6 mm, packed with octadecylsilane bonded to porous silica (5 µm).
- Mobile phase: a mixture of 14 volumes of triethylamine, 300 volumes of acetonitrile and 686 volumes of a 0.075 per cent w/v solution of sodium methanesulphonate, adjusting pH 2.7 with sulphuric acid,
- Flow rate: 1 ml per minute.
- Spectrophotometer set at 230 nm,
- Injection volume: about 20 µl
Inject reference solution (b). The test is not valid unless the peak-to-valley ratio is not less than 10, where Hp is the height above the baseline of the peak immediately before the peak due to Hydroxyzine and Hv is the height above the baseline of the lower point of the curve separating this peak from the peak due to Hydroxyzine. Inject the reference solution (a) and the test solution.
Determine the weight per ml of the oral solution and calculate the content of Hydroxyzine HCl.
Acceptance criteria: 95.0%-105.0%
9.0) 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
CFU: Colony Forming Unit
mg: Milligram
HCl: Hydrochloric Acid
ml: Millilitre
w/v: Weight/Volume
inHg: Inch of Mercury
