Dibasic Calcium Phosphate Dihydrate

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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Nonharmonized attributes: Packaging and Storage, Limit of Fluoride, Iron

Specific local attributes: Identification C (EP), Lead (USP), Description (JP)

CaHPO₄ · 2H₂O  172.09

Phosphoric acid, calcium salt (1:1);

Calcium phosphate, dihydrate (1:1) CAS RN®: 7789-77-7.

1 DEFINITION

Dibasic Calcium Phosphate Dihydrate contains two molecules of water of hydration. It contains NLT 98.0% and NMT 105.0% of dibasic calcium phosphate dihydrate (CaHPO₄ · 2H₂O).

2 IDENTIFICATION

2.1 A.

Sample: 0.1 g of Dibasic Calcium Phosphate Dihydrate

Analysis: Dissolve the Sample by warming in 10 mL of 2 N hydrochloric acid. Add 2.5 mL of ammonia TS dropwise, with shaking, and then add 5 mL of ammonium oxalate TS.

Acceptance criteria: A white precipitate is formed.

2.2 B.

Sample: 0.1 g of Dibasic Calcium Phosphate Dihydrate

Analysis: Dissolve the Sample in 5 mL of diluted nitric acid. Warm the solution to 70°, and add 2 mL of 10% ammonium molybdate solution (freshly prepared).

Acceptance criteria: A yellow precipitate of ammonium phosphomolybdate is formed.

3 ASSAY

3.1 Procedure

Buffer: Dissolve 53.5 g of ammonium chloride with sufficient water in a 1000-mL volumetric flask. Add 570 mL of ammonia water, stronger, and dilute with water to volume. The pH of this solution is 10.7.

Sample solution: Transfer 400 mg of Dibasic Calcium Phosphate Dihydrate to a 200-mL volumetric flask. Dissolve in 12 mL of diluted hydrochloric acid with the aid of gentle heat, if necessary, and dilute with water to volume.

Blank: 20 mL of water containing 1.2 mL of diluted hydrochloric acid

Titrimetric system

• (See Titrimetry 〈541〉.)
• Mode: Residual titration
• Titrant: 0.02 M edetate disodium VS
• Back-titrant: 0.02 M zinc sulfate VS
• Endpoint detection: Visual

Analysis: To 20.0 mL of the Sample solution add 25.0 mL of Titrant, 50 mL of water, and 5 mL of Buffer. Add 25 mg of eriochrome black T–sodium chloride indicator. Titrate the excess Titrant with the Back-titrant. Perform a Blank determination in the same manner.

Calculate the percentage of dibasic calcium phosphate dihydrate (CaHPO₄ · 2H₂O) in the sample taken:

Result = {[(V_B − V_S) × M × F]/W} × 100

V_B = Back-titrant volume consumed by the Blank (mL)

V_S = Back-titrant volume consumed by the Sample (mL)

M = actual molarity of the Back-titrant (mM/mL)

F = equivalency factor, 172.1 mg/mM

W = Sample weight (mg) in 20.0 mL of the Sample solution

Acceptance criteria: 98.0%–105.0%

4 IMPURITIES

4.1 Carbonate

Sample: 1.0 g of Dibasic Calcium Phosphate Dihydrate

Analysis: Mix the Sample with 5 mL of carbon dioxide-free water, and immediately add 2 mL of hydrochloric acid.

Acceptance criteria: No effervescence occurs.

4.2 Chloride and Sulfate, Chloride 〈221〉

Standard: 0.70 mL of 0.010 N hydrochloric acid

Sample: 0.2 g of Dibasic Calcium Phosphate Dihydrate

Analysis: To the Sample add 20 mL of water and 13 mL of diluted nitric acid, and warm gently, if necessary, to completely dissolve. Dilute with water to 100 mL, and filter if necessary. To 50 mL of the filtrate add 1 mL of silver nitrate TS.

Acceptance criteria: The turbidity of the Sample does not exceed that of the Standard (NMT 0.25%).

4.3 Chloride and Sulfate, Sulfate 〈221〉

Standard: 1.0 mL of 0.010 N sulfuric acid

Sample: 0.5 g of Dibasic Calcium Phosphate Dihydrate

Analysis: To the Sample add 5 mL of water and 5 mL of diluted hydrochloric acid, and warm gently, if necessary, to completely dissolve. Dilute with water to 100 mL, and filter if necessary. To 20 mL of the filtrate add 1 mL of diluted hydrochloric acid, and dilute with water to 50 mL. Add 1 mL of barium chloride TS.

Acceptance criteria: The turbidity of the Sample does not exceed that of the Standard (NMT 0.5%).

4.4 Arsenic 〈211〉, Procedures, Procedure 1

Test preparation: 1.0 g in 25 mL of 3 N hydrochloric acid, diluted with water to 55 mL. Omit the addition of 20 mL of 7 N sulfuric acid specified in Procedure.

Acceptance criteria: NMT 3 µg/g

4.5 Barium

Sample: 0.5 g Dibasic Calcium Phosphate Dihydrate

Analysis: Heat the Sample to boiling with 10 mL of water, and add 1 mL of hydrochloric acid dropwise, stirring after each addition. Allow to cool, and filter, if necessary. To the filtrate add 2 mL of potassium sulfate TS.

Acceptance criteria: No turbidity is produced within 10 min.

4.6 Limit of Acid-Insoluble Substances

Sample solution: Dissolve 5.0 g in a mixture of 40 mL of water and 10 mL of hydrochloric acid by boiling gently for 5 min.

Analysis: After cooling, collect the insoluble substance on ashless filter paper, and wash with water until the last washing does not give a reaction for chloride (no turbidity results from the addition of silver nitrate TS). Ignite to completely incinerate the residue and the ashless filter paper at 600 ± 50°.

Acceptance criteria: The weight of the residue does not exceed 10 mg (NMT 0.2%).

4.7 Limit of Fluoride

[Note-Prepare and store all solutions in plastic containers.]

Buffer solution: 294 mg/mL of sodium citrate dihydrate in water

Standard stock solution: 1.1052 mg/mL of USP Sodium Fluoride RS in water

Standard solution: Transfer 20.0 mL of Standard stock solution to a 100-mL volumetric flask containing 50.0 mL of Buffer solution, dilute with water to volume, and mix. Each mL of this solution contains 100 µg of fluoride ion.

Sample solution: Transfer 2.0 g of Dibasic Calcium Phosphate dihydrate to a beaker containing a plastic-coated stirring bar. Add 20 mL of water and 2.0 mL of hydrochloric acid, and stir until dissolved. Add 50.0 mL of Buffer solution and sufficient water to make 100 mL.

Electrode system: Use a fluoride-specific ion-indicating electrode and a silver–silver chloride reference electrode connected to a pH meter capable of measuring potentials with a minimum reproducibility of ±0.2 mV (see pH 〈791〉).

Analysis

Samples: Standard solution and Sample solution

Standard response line: Transfer 50.0 mL of Buffer solution and 2.0 mL of hydrochloric acid to a beaker, and add water to make 100 mL. Add a plastic-coated stirring bar, insert the electrodes into the solution, stir for 15 min, and read the potential in mV. Continue stirring, and at 5-min intervals add 100, 100, 300, and 500 µL of Standard solution, reading the potential 5 min after each addition. Plot the logarithms of the cumulative fluoride ion concentrations (0.1, 0.2, 0.5, and 1.0 µg/mL) versus potential in mV.

Rinse and dry the electrodes, insert them into the Sample solution, stir for 5 min, and read the potential in mV. From the measured potential and the Standard response line determine the concentration, C (in µg/mL), of fluoride ion in the Sample solution.

Calculate the content of fluoride (ppm) in the portion of Dibasic Calcium Phosphate Dihydrate taken:

Result = (V × C)/W

V = Sample solution volume (mL)

C = concentration of fluoride ion, determined from the Standard response line, in the Sample solution (µg/mL)

W = weight of Dibasic Calcium Phosphate Dihydrate taken to prepare the Sample solution (g)

Acceptance criteria: NMT 50 ppm

5 SPECIFIC TESTS

5.1 Loss on Ignition 〈733〉

Sample: 1 g of Dibasic Calcium Phosphate Dihydrate

Analysis: Ignite the Sample at 800°–825° to constant weight.

Acceptance criteria: 24.5%–26.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. No storage requirements specified.

USP Reference Standards 〈11〉

USP Sodium Fluoride RS