Clarithromycin (Micronized) Raw Material Testing Procedure specification & analysis prescribes the requirements for Clarithromycin (Micronized), which is one of the components of tablet. It is applicable in Material Department, Product Development and Quality Assurance Department to confirm its physical and chemical specifications.
1.0 PURPOSE
This raw material specification & analysis prescribes the requirements for Clarithromycin (Micronized), which is one of the components of tablet. .
2.0 SCOPE
It is applicable in Material Department, Product Development and Quality Assurance Department to confirm its physical and chemical specifications.
3.0 REFERENCES
USP/Inhouse
4.0 DEFINITIONS
Follow Company Quality Manual
5.0 SPECIFICATIONS
USP/Inhouse
TESTS SPECIFICATIONS
PHYSICAL ANALYSIS
- Physical Form Crystalline powder
- Colour Should be white to almost white
- pH Should be 7.5—10 at 25°C +- 2°
- Moisture contents Not more than 2%
- Water Contents(by karl Fischer) Not more then 25.
- Optical Rotation -89° to –95°
- Bulk Density 0.300 – 0.500 g/ml
- Tapped Density 0.350 – 0.600 g/ml
CHEMICAL ANALYSIS
- Identification of Clarithromycin Fine examination by IR spectrum: Should comply the standard spectrum
- Identification of clorithromycin: The chloroform layer is coloured purple
- Contents of Clarithromycin: Should be 96—104% calculated with reference to dried substance
6.0 SAMPLING
Refer to the Incoming SOPs for sampling
7.0 REJECTIONS:
If the Clarithromycin(fine) does not satisfy the specifications mentioned in 5.0 then it will be rejected. In addition to the specifications, Clarithromycin(fine) is also rejected due to the following reasons:
7.1 If the receiving raw material is cross contaminated due to any reason.
7.2 The material does not bear 75% of its stated shelf life at the time of receipt.
8.0 PACKAGING
Clarithromycin (Micronized) is received in plastic container to protect it from light.
9.0 STORAGE: USP
Preserve in tight container.
10.0 HANDLING
10.1 Use gloves & mask during weighing and dispensing operation of Clarithromycin(fine)
10.2 Keep the container of Clarithromycin (Micronized) well closed immediately after use.
10.3 Place the container of Clarithromycin (Micronized) back to its specified area.
11.0 ANALYSIS
11.1 (A) Suitable Machinery/Equipment/Apparatus
PHYSICAL CHEMICAL
- Beaker
- Test tubes
- Glass Rod
- 250 ml Titration Flask
- Moisture Analyzer
- Pipette 50 ml (Bulb Type)
- Graduated Pipette 10 ml
- PH Meter
- Burette 50 ml
- Measuring Cylinder
- Analytical Balance
- Magnetic Stirrer
- Polarimeter FTIR,
- Mortar & Pestle
11.1 (B) List Of Reagent/Chemical
Chemicals
- Methanol 30 ml
- Potassium bromide IR grade 200 mg
- Acetic Acid Glacial 200 ml
Reagents
- 0.1 N Per Chloric Acid 100 ml
- Crystal violet 10 ml
PHYSICAL ANALYSIS /Inhouse
Test of Physical Form:
Check the sample and confirm its physical form; it should be crystalline powder.
11.2.2 Test of Colour:
Confirm the colour of the material by comparing with standard from colour chart; it should be white to almost white.
11.2.3 Test of Loss on Drying:
Weigh accurately 10 g of sample on moisture balance. Adjust the temperature at 100°C, start drying the sample. At the end balance show percentage loss of moisture; moisture contents should not be more than 2.0%.
11.2.4 Water Contents:
Weigh accurately 50mg of sample and titrate for Karl Fischer water determination it should be not more than 2%.
11.2.5 Test of pH:
Dissolve 3.5g in 500ml of suspension (mixture of water and methanol 19:1) and measure the pH, it should be between 7.5—10 at 25°C +- 2°.
11.2.6 Optical Rotation:
Prepare 1% W/V solution of clarithromycin in chloroform at 20°C on anhydrous basis. It should be on –89.0° to –95.0°.
11.2.7 Bulk Density:
Take sample in the measuring cylinder, the surface level of the sample in the cylinder should be even, note the volume without tapping, it should be between 0.300 – 0.500 g/ml.
11.2.8 Tapped Density:
Take sample in the measuring cylinder, the surface level of the sample in the cylinder should be even, note the volume with tapping, it should be between 0.350 – 0.600 gm/ml.
11.3 Record the result of Physical Analysis on quality report.
11.4 CHEMICAL ANALYSIS: USP/Inhouse
11.4.1 Examination of Clarithromycin Fine by IR spectrum:
Take dried sample to 5mg of Clarithromycin Fine and thoroughly mix with 95mg of dried standard of potassium bromide in pastel mortar.
Fill Macro cups with provided funnel like instrument and draw the spectrum it should comply with the standard spectrum.
11.4.2 Identification Test of Clarithromycin :
Dissolve 10mg of sample in 6ml of acetone and add 6ml of hydrochloric acid an orange colour is produced, which changes to red and then to a deep purplish red. Add 6ml of chloroform the chloroform layer is coloured purple.
11.4.3 Contents of Clarithromycin Fine:
Sample Preparation:
Dissolve about 500 mg of Clarithromycin, accurately weighed, in 100 ml of glacial acetic acid and 0.2 ml of add crystal violet TS, and titrate with o.1 N per-chloric acid VS (the colour change at the endpoint is from blue to blue-green). Perform a blank determination, and make any necessary correction. Each ml of 0.1 N per-chloric acid is equivalent of 74.797 mg of Clarithromycin.
Limit: The contents of Clarithromycin should be between 96-104%. (Calculated with reference to dried substance).
11.5 Record the result of Chemical Analysis on quality report.
Note. Incase of any non- conformance observed during Inspection and testing , Please Follow Quality System Procedure for Control of Non-Conforming Product. (CCL-CQP-010)
11.6 Total No. of Worker/OFFICER and Time
Officer = 2 Worker = 3 Total Time consumed = 1:00 Hours