Method of Analysis for Dibasic Calcium Phosphate Dihydrate : Pharmaceutical Guidelines

Method of Analysis for Dibasic Calcium Phosphate Dihydrate

Procedure of analysis for Dibasic Calcium Phosphate Dihydrate in pharmaceutical quality control laboratory.
1. Description
White to off-white crystalline powder.

2. Solubility
Practically insoluble in water and in ethanol (95%). It dissolves in dilute hydrochloric acid and in nitric acid.

3. Identification
A) Reaction of calcium salts
Reagent required
Ammonium oxalate 2% w/v solution
Dilute acetic acid
Hydrochloric acid
Procedure
Dissolve 0.4g sample with 100 ml water To 5 ml of above 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) Reaction of Phosphates:
Reagent required
2M Nitric acid
Ammonium molybdate solution
Procedure
Test solution: Dissolve 0.1 g in a mixture of 5 ml of 2M nitric acid and 5 ml of water.
To 2 ml of the prescribed solution add 2 ml of dilute nitric acid and 4 ml of ammonium molybdate solution and warm the solution. A bright yellow precipitate is formed.

4. Acid insoluble substances
Limit: Not more than 0.1%.
Reagent required
Hydrochloric acid
Procedure
Dissolve 5.0g sample with a mixture of 40 ml of water and 10 ml of hydrochloric acid and dilute 100 ml with water. Filter through a filter paper, and wash with hot water until the last washing is free from chloride and dry the residue at 105° for 1 hour.
Calculation:

                                                            Wt. of Residue in gm x 100
% Acid insoluble substances =  ---------------------------------
                                                                    Sample Wt. in gm

5. Arsenic
Limit: Not more than 10 ppm.
Reagent required
Brominated hydrochloric acid
Stannous chloride solution
Lead acetate cotton
Mercuric chloride paper
1M potassium iodide
Arsenic standard solution (10 ppm As)
Zinc Granulated
Test Solution: Dissolve 1.0 g sample in 15 ml of brominated hydrochloric acid, add 45 ml of water and remove the excess of bromine with a few drops of stannous chloride solution.
Procedure
Into the bottle or conical flask introduce the test solution prepared, add 5 ml of 1M potassium iodide and 10 g of zinc AsT. 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 1.0 ml of arsenic standard solution (10 ppm As) diluted to 50 ml with water.

6. Heavy metals
Limit: Not more than 40 ppm.
Reagent required
Dilute acetic acid (Dilute 6 ml Acetic Acid with 100 ml water)
Dilute ammonia solution (Dilute 10 ml ammonia with 100 ml water)  
2M hydrochloric acid (Dilute 8.5 conc. HCl with 50 ml water)
Lead standard solution (20 ppm Pb)
Hydrogen sulfide solution (freshly prepared)
6M Ammonia
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.
Test Solution: 10 ml of the solution prepared in the following manner.
Dissolve 2.5 g in 20 ml of 2M hydrochloric acid, and add 6M ammonia until a precipitate is formed. Add 2M hydrochloric acid just enough to dissolve the precipitate and dilute to 50 ml with distilled water (solution A).
Procedure
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 color produced with the test solution is not more intense than that produced with the standard solution.

7. Barium
Limit: The solution is not more opalescent than standard preparation. 
Reagent required
1M Sulphuric acid
Procedure
To each of the test tube containing the 10 ml of solution A and 0.5 ml 1M sulphuric acid and 10 ml of Solution A and 0.5 ml distilled water. Kept aside test tubes for 15 min.

8. Iron
Limit: Not more than 400 ppm
Reagent required
20% w/v Citric acid solution (iron-free) Thioglycollic acid
Ammonia solution (iron-free) (Dilute 10 ml ammonia with 100 ml water)  
Iron standard solution (20 ppm Fe)
Procedure
Transfer a 2 ml of solution A diluted to 10 ml with water, in Nessler Cylinder. Add 2 ml of a 20% w/v solution of iron-free citric acid and 0.1 ml of Thioglycolic acid, mix, make alkaline with iron-free ammonia solution, dilute to 50 ml with water and allow standing for 5 minutes. Any color produced is not more intense than that obtained by treating in the same manner 2.0 ml of iron standard solution (20 ppm Fe) in place of the solution being examined.

9. Carbonates
Limit: No effervescence is produced.
Reagent required
Hydrochloric acid
Procedure
Suspend 1 g in 5 ml of water and add 2 ml of hydrochloric acid. No effervescence is produced.

10. Chlorides
Limit: Not more than 0.125%.
Reagent required
Nitric acid
0.1M Silver nitrate.
Chloride standard solution (25 ppm Cl)
Procedure
Dissolve 0.2 g sample in water by the addition of 2 ml of nitric acid, dilute to 50 ml with water and add 1 ml of 0.1M silver nitrate. Stir immediately with a glass rod and allow to stand for 5 minutes protected from light. When viewed transversely against a black background any opalescence produced is not more intense than that obtained by treating a mixture of 10 ml of chloride standard solution (25 ppm Cl) and 5 ml of water in the same.

11. Sulphate
Limit: Not more than 0.5%.
Reagent required
Barium chloride solution 25.0% w/v
Ethanolic sulfate standard solution (10 ppm SO4)
5M Acetic acid. (Dilute 30 ml Acetic acid with 100 ml water)
Sulfate standard solution (10 ppm SO4)
Procedure
Test Solution: Dissolve 30 mg sample in 25 ml water by addition of 2 ml of hydrochloric acid. To 1.0 ml of a 25.0% w/v solution of barium chloride in a Nessler cylinder add 1.5 ml of ethanolic sulfate standard solution (10 ppm SO4), mix and allow standing for 1 minute. Add 15 ml of the test solution and 0.15 ml of 5M acetic acid. Add sufficient water to produce 50 ml, stir immediately with a glass rod and allow standing for 5 minutes. When viewed transversely against a black background any opalescence produced is not more intense than that obtained by treating in the same manner
Standard Solution: 15 ml of sulfate standard solution (10 ppm SO4) in place of the solution being examined.

12. Nitrate
Limit: The blue color should not disappear.
Reagent required
Sulphuric acid (Nitrogen-free)
Indigo carmine solution
Procedure
To 0.1 g add 10 ml of water, 10 ml of nitrogen-free sulphuric acid and 1 ml of indigo carmine solution and heat to boiling; blue color does not disappear.

13. Loss on Ignition
Limit: Between 24.5 and 26.5%
Procedure
Weigh a silica or platinum crucible, complete with the lid, previously ignited for 1 hour at the 500° temperature for the test and cooled in desiccators. Transfer to the crucible 1 g of the substance, without any treatment Weigh accurately the crucible, lid and the contents. Place the loaded uncovered crucible and cover in a suitable muffle furnace or oven that is capable of maintaining a temperature 500°±25°. Ignite the crucible to constant weight. Ignite for successive 1-hour periods where ignition to constant weight is indicated. Upon the completion of each ignition, cover the crucible and allow it to cool in desiccators to room temperature before weighing.
Calculation:

                        Loss of Ignition in gm x 100
% LOI =    ----------------------------------
                               Wt. of Sample in gm

14. Portentous impurities
Limit: No unpleasant odor is emitted.
Procedure
Heat 0.5 g gently in a dry test-tube; no change in color is observed and no unpleasant odor is emitted.     

15. Reducing substance
Limit: The color is not less intense than the treated standard.
Reagent required
0.005M Potassium permanganate (Dissolve 0.0079 g Potassium- Permanganate with 1000 ml water
Calcium carbonate
3M Sulphuric acid
Procedure
Shake 1 g with 5 ml of water and 5 ml of 3M sulphuric acid for 1 minute. Add 0.1 ml of 0.005M potassium permanganate and shake for 20 seconds. The slightly pink color is not less intense than that produced by treating 1 g of calcium carbonate in the same manner.

16. Fluorides
Limit: Not more than 100 ppm
Reagent required
Sulphuric acid (50% v/v)
0.1M Sodium hydroxide
Aminomethylalizarindiacetic acid
Phenolphthalein solution
Fluoride standard solution (10 ppm F)
Procedure
Introduce into the inner tube of the apparatus the specified 0.5 g sample 0.1 g of acid-washed sand and 20 ml of sulphuric acid (50% v/v). Place tetrachloroethane in the outer jacket and heat to maintain at its boiling point (146°). Attach a steam generator and distil, collecting the distillate in a 100-ml graduated flask containing 0.3 ml of 0.1M sodium hydroxide and 0.1 ml of phenolphthalein solution. Maintain a constant volume (20 ml) in the tube during distillation and ensure that the distillate remains alkaline, adding 0.1M sodium hydroxide if necessary. Dilute the distillate to 100 ml with water. Prepare a standard by distillation, in the same manner, using 5ml of fluoride standard solution (10 ppm F) in place of the substance being examined. Into two glass-stoppered cylinders separately place 20ml of the test solution and 20 ml of the standard and add 5ml of aminomethylalizarindiacetic acid reagent to each solution. After 20 minutes any blue color in the test solution (originally red) is not more intense than that in the standard solution

17. Monocalcium and Tricalcium phosphates
Limit: NLT 11.0 ml and NMT 12.5 ml of 1 M Hydrochloric acid are required.
Reagent required
1M Hydrochloric acid
Methyl orange solution
1M Sodium hydroxide solution
Procedure
Dissolve about 2 gm of the sample in 30 ml of 1 M Hydrochloric acid. Add 20 ml of water and 0.05 ml of methyl orange solution. Titrate the excess of acid with 1 M Sodium Hydroxide.

18. Assay
Limit: NLT 98.0 % and NMT 105.0 % of CaHPO4.2H2O
Reagent required
7M Hydrochloric acid,
0.1M Disodium Edetate
Ammonia Buffer pH 10.0
Strong Ammonia Solution
0.1M Zinc sulfate
Mordant Black II mixture
Procedure
Weigh accurately about 0.3 g and dissolve in a mixture of 5 ml of water and 1 ml of 7M Hydrochloric acid, add 25.0 ml of 0.1 M Disodium edetate and dilute to 200 ml with water. Neutralize with strong ammonia solution, add 10 ml of ammonia buffer pH 10.0 and 50 mg of mordant black 11 mixture and titrate the excess of Disodium Edetate with 0.1 M zinc sulfate. Each ml of 0.1M Disodium edetate is equivalent to 0.01721 g of CaHPO4, 2H2O.
 Calculation:
                           (B – T) x M x F x100
% Assay  =  -------------------------------
                               0.1 x Wt. of sample

Where,
B = Blank reading
T = Test Reading
M = Molarity of 0.1 M Zinc Sulphate
F = Factor





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.
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