Atorvastatin Calcium Raw Material Testing Procedure is taken as a raw material, and the product refined by a mixed solvent is crystallized to obtain high-purity atorvastatin calcium trihydrate. The preparation method provided by the invention is suitable for industrial production.
PURPOSE
This raw material specification and analysis prescribes the requirements for Atorvastatin Calcium, which is one of the components of “Atorvastatin Calcium” 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
Merck Index/ Martindale/ Manufacturer specification /In-House Specification
4.0 DEFINATIONS
Company Quality Manual
5.0 SPECIFICATIONS Reference Manufacturer specification.
PHYSICAL ANALYSIS
- Physical Form: Crystalline Powder
- Colour: White or Almost white
- Solubility: Soluble in methanol, Slightly soluble in water and in ethanol.
- Moisture contents: 3.5—5.5%
- Water Contents: Between
CHEMICAL ANALYSIS
- Identification of Atorvastatin Calcium examination by IR spectrum: Should comply the standard spectrum
- Identification of Calcium: White Precipitates should produce
- Content of Atorvastatin Calcium: Should be between 97.0—102.0 % (On dry basis)
SAMPLING
Refer to the Incoming SOPs for sampling.
7.0 REJECTIONS:
If the Atorvastatin Calcium does not satisfy the specifications mentioned in 5.0 then it will be rejected. In addition to the specifications, Atorvastatin Calcium 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
8.1 Atorvastatin Calcium is received in thick aluminum foil bags placed in cardboard container to protect it from moisture and light.
9.0 STORAGE Reference In-House Specification.
9.1 Should be kept in an airtight container, Protected from light and stored at a Temperature not exceeding 25°C.
10.0 HANDLING
10.1 Use gloves & mask during weighing and dispensing operation of Atorvastatin Calcium.
10.2 Keep the container of Atorvastatin Calcium well closed immediately after use.
10.3 Place the container of Atorvastatin Calcium, back to its specified area.
11.0 ANALYSIS
11.1 (A) Suitable Machinery/Equipment/Apparatus
PHYSICAL
- Moisture Balance
- Analytical Balance
- Test Tubes
- Beaker
- Glass Rod
CHEMICAL
- Graduated Pipette 1 ml
- Volumetric Flasks 100ml
- Funnels
- Analytical Balance
- Spatula
- Titration flasks 100ml
- FTIR
- UV-VIS Spectrophotometer
Chemicals
- Methanol 500 ml
- Ethanol 20 ml
- Potassium Bromide 200mg
11.2 PHYSICAL ANALYSIS Reference Manufacturer specification
11.2.1 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 or almost white.
11.2.3 Test of Solubility:
Check the solubility of the sample in Methanol, Ethanol and Water
It should be Soluble in Methanol, Slightly Soluble in water and ethanol.
11.2.4 Test of Moisture Contents:
Weigh accurately 10 g of sample on moisture balance. Adjust the temperature at 105°C, start drying the sample. At the end balance show percentage loss of water; water contents should be between 3.5—5.5%.
11.2.5 Water Contents:
Weigh accurately 50mg of sample and titrate for Karl Fischer water determination it should be between 3.5 to 5.5%.
11.2.6 Record the result of Physical Analysis on Quality Report.
11.3 CHEMICAL ANALYSIS: Reference Martindale/ In-House Specification
11.3.1 Examination of Atorvastatin Calcium by IR spectrum:
Take dried sample to 5mg of Atorvastatin Calcium 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 be complies the standard spectrum.
11.3.2 Identification test of Calcium
Weigh accurately on analytical balance 20mg of the sample, put it in test tube, add 2ml of methanol and 1 ml of Ammonium Oxalate TS; White Precipitates should produce which are insoluble in dilute Acetic Acid and Ammonia but Soluble in dilute Hydrochloric Acid.
11.3.3 Contents of Atorvastatin Calcium:
11.3.3.1 Standard Preparation
Weigh accurately on analytical balance Atorvastatin Calcium equivalent to 100 mg of Atorvastatin calcium in 100 ml volumetric flask. Add 20ml of methanol dissolve it by Sonication and make up the volume up to 100 ml with methanol. Pipette 1 ml to 100 ml volumetric flask , make up the volume up to 100 ml with methanol and filter it in 100 ml titration flask. Measure the Absorbance at 246 nm by UV-Spectrophotometer. 100 mg of Atorvastatin calium=104.67 mg of Atorvastatin Calcium (Trihydrate)
11.3.3.2 Sample Preparation
Weigh accurately on analytical balance 100 mg sample of Atorvastatin calcium in 100 ml volumetric flask. Add 20ml of methanol, dissolve it by Sonication and make up the volume up to 100 ml with methanol. Pipette 1 ml to 100 ml volumetric flask , make up the volume up to 100 ml with methanol and filter it in 100 ml titration flask. Measure the Absorbance at 246 nm by UV-Spectrophotometer.
11.3.3.3 Blank Preparation
Take 40 ml of methanol and filter it in 100 ml titration flask and Measure the absorbance of blank at 246 nm on U.V Spectrophotometer.
11.3.3.4 Observations:
a) Absorbance of the sample = A
b) Absorption of the standard = B
11.3.3.5 Calculations
A
——————— x 100 = C
B
11.3.3.6 Limit: The contents of Atorvastatin Calcium should be 97.0 to 102 % on dried
basis.
11.3.3.7 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.
12.0 TOTAL NO. OF WORKER/OFFICER AND TIME
i- Officer 2 ii- worker 2 Total Time 2.00 Hrs