## STP FOR CLARITHROMYCIN ORAL SUSPENSION

1.0) Description: Light orange color powder filled in 30ml HDPE bottle which on reconstitution gives orange colour liquid.

2.0) Average Net weight of powder:

Select a sample of 10 filled containers and remove any labeling that might be altered in weight while removing the contents of the containers. Clean and dry the outer surfaces of the containers and weigh each container. If necessary, cut open the container and wash each empty container with a suitable solvent, taking care to ensure that the closure and other parts of the container are retained. Dry and again weigh each empty container together with its parts which may have been removed. The difference between two weights is the net weight of the contents of the container. Calculate the average net weight of the contents of the 10 containers by formula          :  wt of 10 container (gm) x 1000 / 10. found avg. wt in mg

3.0) Uniformity of weight:

Select a sample of 10 filled containers and remove any labeling that might be altered in weight while removing the contents of the containers. Clean and dry the outer surfaces of the containers and weigh each container. If necessary, cut open the container and wash each empty container with a suitable solvent, taking care to ensure that the closure and other parts of the container are retained. Dry and again weigh each empty container together with its parts which may have been removed. The difference between two weights is the net weight of the contents of the container.

The average net weigh of the contents of the 10 containers is not less than the labelled amount and the net weight of the contents of ant 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 50g or less, or not less than 955 per cent and not more than 104.5 per cent of the labeled amount where the labeled amount is more than 50g but not more than 100g.

If this requirement is not met, determine the net weight of the contents of 10 additional containers. The average net weight of the contents of the 20 containers is not less than the labeled amount, and the net weight of the contents of not more than 1 of the 20 containers is less than 91 per cent or more than 109 per cent of the labeled amount where the labeled amount is 50g or less than 95.5 per cent or more than 100g. None of individual weights deviates by more than twice that of respective minimum and maximum percentage limits.

4.0) Identification Test:

The retention time of the major peak of the sample solution corresponds to that of the standard solution, as obtained in the assay.

5.0)      pH:

Use the suspension constituted as directed in the labeling.

Acceptance criteria: 4.0-5.4

6.0) Loss on drying:

Sample: 1g

Analysis: Dry under vacuum at a pressure not exceeding 5mm of mercury at 60° for 3 hours.

Acceptance criteria: N.M.T. 2.0%

7.0) 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.

8.0)      Assay: Determined by liquid chromatography.

Buffer: 0.067 M Monobasic potassium phosphate.

Mobile phase: Methanol and buffer (60:40), adjusted with phosphoric acid to a pH of 3.5. Pass through a suitable filter.

Standard stock solution: Equivalent to 2.1 mg/ml of clarithromycin from USP clarithromycin reference standard in methanol.

Standard solution: 0.415 mg/ml of clarithromycin from standard stock solution in mobile phase.

Sample stock solution: Constitute the clarithromycin for oral suspension as directed in the labeling. Transfer an aliquot of the suspension, equivalent to 1-2 g of clarithromycin, with the aid of 330ml of buffer, to a 1000ml volumetric flask containing 50ml of buffer. Shake by mechanical means for 30 minutes, and dilute with methanol to volume. Sonicate for about 30 minutes and allow to cool. Dilute with methanol to volume, add a magnetic stirring bar, and stir for 60 minutes. Allow to settle and use the clear supernatant.

Sample solution: Transfer an aliquot of the sample stock solution, nominally equivalent to 20mg of clarithromycin, to a 50ml volumetric flask, dilute with mobile phase to volume, and pass through a suitable filter.

Chromatographic system:

• A stainless steel column 15cm X4.6mm, packing L1
• Flow rate: 1ml per minute,
• Spectrophotometer set at 210nm,
• Injection volume: 50µl
• Column temperature: 50°
• System suitability requirements: Tailing factor: 1.0-1.7

Relative standard deviation: NMT 2.0%

Calculate the percentage of the labeled amount of clarithromycin in the portion of the

constituted clarithromycin for oral suspension taken.

Result:  ( rv/rs ) x (cs/cv) x100

rv: peak area response from the sample solution

rs: peak area response from standard solution

cs:  concentration of the standard dolution (mg/ml)

cv: nominal concentration of clarithromycin in the sample solution (mg/ml)

Acceptance criteria: 90.0%-115.0%

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

mg: Milligram

ml: Millilitre

STD: Standard

inHg: Inch of Mercury

rpm: Rotations per minute

CFU: Colony forming unit

w/v: Weight/Volume