Method of Analysis for Citric Acid Anhydrous : Pharmaceutical Guidelines

Method of Analysis for Citric Acid Anhydrous

Learn how to analyse Citric Acid Anhydrous in pharmaceutical laboratory.

1. Description
A white, crystalline powder, colorless crystals or granules.

2. Solubility
Very soluble in water, freely soluble in alcohol, sparingly soluble in ether.

3. Identification
A. Dissolve 1 g in 10 ml of water. The solution is strongly acidic
B. Examine by infrared absorption spectrophotometry, comparing with the spectrum obtained with anhydrous citric acid WRS after drying both the substance being examined and the reference substance at 100°C to 105°C for 24 h.
C. Add about 5 mg to a mixture of 1 ml of acetic anhydride and 3ml of pyridine. A red color develops.
D. Dissolve 0.5 g in 5 ml of water R, neutralize using 1M sodium hydroxide (about 7 ml), add 10 ml of calcium chloride solution and heat to boiling. A white precipitate is formed.
E. It complies with the test for water (see Tests).

4. Appearance of the solution
Limit: The solution is clear and not  more intensely colored than reference solution Y7, BY7
Procedure
Test Solution: Dissolve 2.0 g in water and dilute to 10ml with the same solvent.
Reference Solution BY7: Prepare BY solution by mixing 24ml of yellow primary standard solution, 10ml of red primary solution, 4 ml of blue primary solution, 62 ml of 1% w/v of Hydrochloric acid. Now take 2.5 ml of this BY solution in 100ml volumetric flask and make up the volume to 100 ml with 1% w/v solution of hydrochloric acid.
Reference Solution Y7: Prepare Y solution by mixing 24ml of yellow primary standard solution, 6 ml of red primary solution, 70 ml of 1% w/v of Hydrochloric acid. Now take 2.5 ml of this Y solution in 100ml volumetric flask and make up the volume to 100 ml with 1% w/v solution of hydrochloric acid.
Examine the test solutions and reference solutions in diffused daylight by viewing down the vertical axes of the tubes against a white background.

5. Readily Considerable Substances
Limit: The solution is not more intensely colored than a mixture of 1 ml of red primary solution and 9 ml of yellow primary solution.
Procedure
Test Solution Preparation: To 1.0 g in a cleaned test tube add 10 ml of sulphuric acid and immediately heat the mixture in a water bath at 90±1°C for 60 min. Immediately cool rapidly.
Reference Solution Preparation: A mixture of 1 ml of red primary solution and 9 ml of yellow primary solution.
Examine the test solutions and reference solutions in diffused daylight by viewing down the vertical axes of the tubes against a white background.    

6. Oxalic acid
Limit: Not more than 350 ppm on the anhydrous basis.
Procedure
Dissolve 0.80 g in 4 ml of water. Add 3 ml of hydrochloric acid and 1gm of zinc in granules. Boil for 1 min.  Allow standing for 2 min. Transfer the supernatant liquid to a test- tube containing 0.25 ml of a 10-g/l solution of phenyl hydrazine hydrochloride and heat to boiling. Cool rapidly, transfer to a graduated cylinder and add an equal volume of hydrochloric acid and 0.25 ml of a 50-g/l solution of potassium ferricyanide. Shake and allow to stand for 30 min. Any pink color in the solution is not more intense than that in a standard prepared at the same time, in the same manner, using 4 ml of a 0.1 g/l solution of oxalic acid

7. Sulphate
Limit: Not more than 150 ppm
Procedure
Test Solution: Add 1 ml of a 25% w/v solution of barium chloride to 1.5 ml of sulfate standard solution (10 ppm SO4), shake and allow standing for 1 minute. Dissolve 1gm of the sample in distilled water and dilute to 15ml with the water. Add 15ml of this solution to the above solution and then add 0.5 ml of 5M acetic acid and allow standing for 5 minutes.
Reference Solution: Add 1 ml of a 25% w/v solution of barium chloride to 1.5 ml of sulfate standard solution (10 ppm SO4), shake and allow standing for 1 minute. Then add 15ml of sulfate standard solution (10 ppm of SO4) and then add 0.5 ml of 5M acetic acid and allow standing for 5 minutes.
Any opalescence produced by test solution is not more intense than that of a standard solution.

8. Arsenic
Limit: Not more than 1 ppm
Procedure
Test Solution: Dissolve 10gm of the sample in 50 ml of water and add 10 ml of stannated hydrochloric acid.
Into the bottle or conical flask introduce the test solution 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.

9. Barium
Limit: Any opalescent produced by test solution is not more intense than standard solution.
Procedure
Dissolve 5.0 g in several portions in 39 ml of 2M sodium hydroxide and dilute to 50 ml with distilled water (solution A). To 5 ml of solution A add 5 ml of 1M sulphuric acids and allow standing for 1 hour. Any opalescence produced is not more intense than that of a mixture of 5 ml of solution A and 5 ml of distilled water.

10. Calcium
Limit: Not more than 200 ppm
Procedure
To 0.2 ml of ethanolic calcium standard solution (100 ppm Ca) add 1 ml of a 4.0% w/v solution of ammonium oxalate. After 1 minute add 1 ml of 2M acetic acid and 5 ml of solution A diluted to 10 ml with distilled water and shake. After 15 minutes any opalescence produced is not more intense than that of a standard prepared in the same manner using a mixture of 10 ml of calcium standard solution (10 ppm Ca) and 5 ml of water in place of solution A (200 ppm).

11. Iron
Limit: Not more than 50 ppm
Procedure
Dilute 8ml of solution A to 10ml with water, and transfer to a Nessler 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 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.

12. Chloride
Limit: Not more than 50 ppm
Procedure
Dissolve 5.0 g in 10 ml of water, add 1 ml of 2M nitric acid and dilute to 15 ml with water, and transfer to a Nessler cylinder. Add 10 ml of dilute nitric acid, except when nitric acid is used in the preparation of the solution, dilute to 50 ml with water and add 1 ml of 0.1 M 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 10.0 ml of chloride standard solution (25 ppm Cl) and 5 ml of water in the same manner.

13. Heavy metals
Limit: Not more than 10 ppm
Reagent required 
Dilute ammonia
Dilute acetic acid
Hydrogen sulfide solution
Acetate buffer pH 3.5
Lead standard solution (20 ppm Pb)
0.1M Hydrochloric acid
Standard Solution: Pipette out 10 ml of Lead standard solution (1 ppm Pb) in a Nessler cylinder. Then add 2ml of the test solution. To the above solution add 2 ml of acetate buffer pH 3.5, mix, add to 1.2 ml of thioacetamide reagent, mix immediately and allow standing for 2 minutes
Sample Solution: Dissolve 5.0 g in several portions in 39 ml of dilute sodium hydroxide solution and dilute to 50 ml with distilled water. To 12 ml of the above solution add 2 ml of acetate buffer pH 3.5, mix, add to 1.2 ml of thioacetamide reagent, mix immediately and allow standing for 2 minutes
Procedure
Any brown color produced by test solution is not more intense than that obtained by standard solution.

14. Sulphated Ash
Limit: Not more than 0.1%
Procedure
Heat a silica crucible to redness for 10 min., allow cooling in a desiccator and weighing. Place about 1 g of accurately weighed substance being examined in the silica crucible, moisten with sulphuric acid, ignite gently, again moisten with sulphuric acid and ignite at about 800o, cool, weigh again, ignite for 15 min. and repeat this procedure until two successive weighing do not differ by more than 0.5 mg.
Calculation:
                                          W3– W1
% Sulphated ash  =  --------------- X 100
                               W2 – W1
Where:   
W1 = Weight of empty platinum crucible.
W2 = Weight of crucible + sample.
W3 = Weight of crucible + residue. (After ignition)

15. Water
Limit: Not more than 1.0%
Reagent required
Anhydrous methanol AR
KF reagent Pyridine-free single solution
Procedure
Take about 40 ml of anhydrous methanol in the titration vessel, neutralize with KF reagent and find out the factor of KF reagent in mg H2O/ 5 ml in triplicate and enter the mean value. 
Add accurately about 2gm of the sample to the titration vessel. Allow titrating with KF reagent to the electrometric end point. Record the percentage of water content obtained by Karl Fischer titrator. Find out water content of the sample in triplicate and take mean value.

16. Assay
Limit: Not less than 99.5 % and not more than 101% on the anhydrous basis.
Procedure
Dissolve 0.550 gm of the sample in 50 ml of water. Titrate with 1M sodium hydroxide, using 0.5 ml of phenolphthalein solution as indicator.
1 ml of 1M sodium hydroxide is equivalent to 64.03 mg of C6H8O7.
Calculation:
% Assay on dried basis
      B.R.x Actual molarity x 64.03 x 100 x 100         
 = ----------------------------------------------------
      0.1 x Wt of sample in gm x (100-LOD)



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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