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Method of Analysis for Calcium Carbonate


Learn how to analyze the Calcium Carbonate in pharmaceuticals including Substance Insoluble in Acetic acid, LOD and assay.
1. Description
Fine, white, microcrystalline powder
2. Solubility
Practically insoluble in water and in ethanol (95%); slightly soluble in water containing carbon dioxide, or any ammonium salt. It is soluble with effervescence in dilute acids.
3. Identification
A. Test for Calcium
Reaction A: A white crystalline precipitates are produced.
Reaction B: A white precipitate is obtained that is only sparingly soluble in dilute acetic acid but is soluble in hydrochloric acid.
Reagent required
2M acetic acid
Glacial acetic acid
Potassium Ferro cyanide Solution
Ammonium chloride
Ammonium oxalate
Procedure
Dissolve 5.0 g in 80 ml of 2M acetic acid. When effervescence ceases, boil the solution for 2 minutes, allow to cool, dilute to 100 ml with 2M acetic acid and filter, if necessary, through a sintered-glass filter reserving any residue for the test for Substances insoluble in acetic acid; 0.2 ml of the filtrate (solution A) gives reactions A and B of calcium salts.
Reaction A: Take 0.2ml of sample solution to this add 1 ml of glacial acetic acid. Add 0.5 ml of potassium Ferro cyanide solution, the solution remains clear. Add about 50mg of ammonium chloride; a white, crystalline precipitate is formed.
Reaction B: To 0.2ml of the sample solution add 0.2 ml of a 2% w/v solution of ammonium oxalate; a white precipitate is obtained that is only sparingly soluble in dilute acetic acid but is soluble in hydrochloric acid.
B. Test for Carbonate
A white precipitate is formed that dissolves on addition of an excess of dilute hydrochloric acid.
Reagent required
2M acetic acid
0.1 M barium hydroxide
Procedure
Suspend 0.1 g of the substance being examined in a test - tube in 2 ml of water or use 2 ml of the prescribed solution. Add 2 ml of 2M acetic acid, close the tube immediately using a stopper fitted with a glass tube bent at two right - angles, heat gently and collect the gas in 5 ml of 0.1 M barium hydroxide, a white precipitate is formed that dissolves on addition of an excess of dilute hydrochloric acid.
4. Substance Insoluble in Acetic acid
Limit: The residue weights not more than 10 mg
Procedure
Wash any residue obtained in Identification test A with four quantities, each of 5 ml, of hot water and dry at 100o for 1 hour; the residue weighs not more than 10 mg (0.2%).
5. Arsenic
Limit: Not more than 4 ppm
Reagents Required:
Brominated Hydrochloric acid
Stannous chloride
Arsenic standard solution (10 ppm As)
1M potassium iodide
Zinc
Procedure
Test Solution Preparation: Dissolve 2.5 g in 15 ml of brominated hydrochloric acid and 45 ml of water and remove the excess of bromine with a few drops of stannous chloride solution .
Standard Solution Preparation: Take 1.0 ml of arsenic standard solution (10 ppm As) and dilute it to 50 ml with water.
Add 5 ml of 1M potassium iodide and 10 g of zinc granules. Immediately assemble the apparatus and immerse the flask in a water-bath at a temperature such that a uniform evolution of gas is maintained. After 40 minutes any stain produced on the mercuric chloride paper is not more intense than that obtained by treating in the same manner the standard solution.
6. Heavy metals
Limit: Not more than 20 ppm
Reagent required 
Dilute Hydrochloric acid
Dilute Acetic acid
Lead standard solution (20 ppm Pb)
Dilute Ammonia solution
Hydrogen sulphide
Procedure
Test Solution Preparation: To 1 g of sample add 5 ml of water, and 8 ml of dilute hydrochloric acid, the latter being added slowly, shake and evaporate to dryness on a water-bath. Dissolve the residue in 20 ml of water, filter, add to the filtrate 3 ml of dilute acetic acid and water to make 25 ml
Standard solution: Into a 50-ml Nessler cylinder pipette 1.0 ml of lead standard solution (20 ppm Pb) and dilute with water to 25 ml. Adjust with dilute acetic acid or dilute ammonia solution to a pH between 3.0 and 4.0, dilute with water to about 35 ml and mix
To each of the cylinders containing the standard solution and test solution respectively add 10 ml of freshly prepared hydrogen sulphide solution, mix, dilute to 50 ml with water, allow to stand for 5 minutes and view downwards over a white surface; the colour produced with the test solution is not more intense than that produced with the standard solution.
7. Barium
Limit: The solution remains clear for not less than 15 minutes
Reagent required 
2M Acetic acid
Calcium Sulphate Soluion
Procedure
Dissolve 0.6 g in 10 ml of 2M acetic acid by boiling, cool and add 10 ml of calcium sulphate solution; the solution remains clear for not less than 15 minutes
8. Iron
Limit: Not more than 200 ppm
Reagents Required:
Iron free Hydrochloric acid
Iron Standard solution (20 ppm Fe)
20%w/v iron free citric acid solution
Thioglycollic acid
Iron free ammonia solution
Procedure
Test Solution Preparation: Dissolve 0.2 g in 5 ml water and 0.5 ml of Iron-free hydrochloric acid, boil and dilute to 40 ml with water in Nesseler’s cylinder.
Standard Solution Preparation: Take 2.0 ml of iron standard solution (20 ppm Fe) in Nesseler’s cylinder and dilute it to 40ml with water.
To each of the cylinder add 2 ml of 20 % w/v solution of iron-free citric acid and 0.1 ml of thioglycollic acid, mix make alkaline with iron-free ammonia solution, dilute to 50 ml with water and allow to stand for 5 minutes. Any colour produced in the test solution is not more intense than the standard solution.
9. Magnesium and alkali metals
Limit: The residue remains must be not more than 5mg.
Reagent required
Dilute hydrochloric acid
Dilute Ammonia solution
Ammonium Oxalate Solution
Dilute Sulphuric acid
Procedure
Dissolve 1.0 g in 10 ml of dilute hydrochloric acid, neutralize the solution by adding dilute ammonia solution, heat the solution to boiling and add 50 ml of hot ammonium oxalate solution. Cool, dilute to 100 ml with water and filter. To 50 ml of the filtrate add 1.5 ml of dilute sulphuric acid, evaporate to dryness on a water-bath, heat the residue to redness, allow to cool and weigh.
10. Chloride
Limit: Not more than 250 ppm
Reagents Required:
Nitric acid
0.1M Silver Nitrate
Standard Chloride Solution (25 ppm)
Procedure:
Test Solution Preparation: Take 1gm of sample dissolved in water by the addition of 3 ml of nitric acid in Nesseler’s cylinder. Dilute to 50 ml with water and add 1 ml of 0.1 M silver nitrate. Stir immediately with a glass rod and allow standing for 5 minutes protected from light
Standard Solution Preparation: Take 10ml of standard chloride solution (25 ppm) in a Nesseler’s cylinder. Add 3ml of nitric acid solution and dilute it to 50ml with water. Then add 1ml of 0.1M Silver nitrate. Stir immediately with a glass rod and allow standing for 5 minutes protected from light
When viewed transversely against a black background any opalescence produced in the test solution is not more intense than the standard solution.
11. Sulphate
Limit: Not more than 0.25%
Dilute Hydrochloric acid
Sulphate standard solution (10 ppm SO 4)
25.0 % w/v solution of barium chloride
Ethanolic sulphate standard solution (10 ppm SO4)
5M acetic acid
Procedure
Test Solution Preparation: Suspend 50 mg in 5 ml of water and add drop wise sufficient dilute hydrochloric acid to effect solution. Add 2 ml of dilute hydrochloric acid.
Standard Solution Preparation: Take 15 ml of sulphate standard solution (10 ppm SO4)
Take two 50ml Nesseler’s cylinder and add 1.0 ml of a 25.0 % w/v solution of barium chloride in a Nessler cylinder add 1.5 ml of ethanolic sulphate standard solution (10 ppm SO4), mix and allow to stand for 1 minute. Add 15 ml of test preparation in one cylinder and 15ml of standard solution in another cylinder then add 0.15 ml of 5M acetic acid. Add sufficient water to produce 50 ml, stir immediately with a glass rod and allow to stand for 5 minutes. When viewed transversely against a black background any opalescence produced in the test solution is not more intense than that in the standard solution.
12. Loss on Drying
Limit: Not more than 2.0%
Procedure:
Weigh 1.000 g of substance in a clean and dried preweighed LOD Bottle. Cover the stopper and gently shake to distribute material to not more than 10 MM height. Place the LOD Bottle in oven and remove cover and leave it also inside the oven. Dry the sample at 105° C for 4 hr. On opening the chamber, immediately close the LOD Bottle, transfer it to desiccator and bring it to room temperature. Weigh up to constant weight.    
Calculation:
                                               W2 – W1
              % Loss on drying = --------------- X 100
                                               W2 – W3
Where:   
                W1 = Weight of empty clean and dried LOD Bottle.
                W2 = Weight of LOD Bottle + sample.
                W3 = Weight of LOD Bottle + sample. (After drying)

13. Assay
Limit: NLT 98.0% and NMT 100.5% calculated on dried substance
Reagent required
Dilute hydrochloric acid
0.05M Disodium Edetate
Sodium hydroxide solution
Calcon mixture
Procedure               
Weigh accurately about 0.1 g and dissolve in 3 ml of dilute hydrochloric acid and 10 ml of water. Boil for 10 minutes, cool, dilute to 50 ml with water. Titrate with 0.05M Disodium Edetate to within a few ml of the expected end-point, add 8 ml of sodium hydroxide solution and 0.1 g of calcon mixture and continue the titration until the colour of the solution changes from pink to a full blue colour. Each ml of 0.05M Disodium Edetate is equivalent to 0.005004 g of CaCO3.
Calculation:
                                      V x M x F                             100
           % Assay  = ------------------------------- x----------------
                                         0.05 x W                     (100-LOD)
Where,
V  = Blank reading – Sample reading
M = Molarity of 0.05M Disodium Edetate
F  = Factor
W = Weight of sample
Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of Pharmaceutical Guidelines, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
Email: .moc.enilediugamrahp@ofni Need Help: Ask Question


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