Calcium Carbonate Oral Suspension
DEFINITION
Calcium Carbonate Oral Suspension contains NLT 90.0% and NMT 110.0% of the labeled amount of calcium carbonate (CaCO3).
IDENTIFICATION
•  A. Identification Tests—General, Calcium 191: The addition of acetic acid to it produces effervescence (presence of carbonate). The resulting solution, after boiling, meets the requirements.
ASSAY
•  Procedure
Sample solution:  Transfer a portion of Oral Suspension, equivalent to 1 g of calcium carbonate, previously well shaken in its original container, to a beaker with the aid of 25 mL of water. Add 20 mL of 1 N hydrochloric acid. Heat on a steam bath for 30 min. Allow to cool, and transfer with the aid of water to a 100-mL volumetric flask. Dilute with water to volume. Mix, and filter.
Blank:  100 mL of water, 15 mL of 1 N sodium hydroxide, and 5 mL of triethanolamine
Titrimetric system 
Mode:  Direct titration
Titrant:  0.05 M edetate disodium VS
Indicator:  100 mg of hydroxy naphthol blue
Endpoint detection:  Visual, change to distinct blue
Analysis:  Transfer 20.0 mL of the Sample solution to a suitable container. Dilute with water to 100 mL. Add 15 mL of 1 N sodium hydroxide, 5 mL of triethanolamine, and 100 mg of hydroxy naphthol blue. Titrate with the Titrant.
Calculate the percentage of the labeled amount of calcium carbonate (CaCO3) in the sample taken:
Result = [(VS VB) × M × F × 100]/W
VS== volume of the Titrant consumed by the Sample solution (mL)
VB== volume of the Titrant consumed by the Blank (mL)
M== Titrant molarity (mmol/mL)
F== equivalency factor, 100.09 mg/mmol
W== nominal amount of calcium carbonate taken for the Analysis (mg)
Acceptance criteria:  90.0%–110.0%
IMPURITIES
•  Limit of Fluoride
[Note—Prepare and store all solutions in plastic containers. ]
Solution A:  294 mg/mL of sodium citrate dihydrate in water
Standard stock solution:  1.1 mg/mL of USP Sodium Fluoride RS in water
Standard solution:  Combine 20.0 mL of the Standard stock solution with 50.0 mL of Solution A, and dilute with water to 100.0 mL. [Note—Each mL of this solution contains 100 µg of fluoride ion. ]
Sample solution:  Transfer a portion of Oral Suspension, equivalent to 2.0 g of calcium carbonate, to a beaker containing a plastic-coated stirring bar. Add 20 mL of water and 4.0 mL of hydrochloric acid. Stir until dissolved. Add 50.0 mL of Solution A and sufficient water to make 100.0 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).
Standard response line:  Transfer 50.0 mL of Solution A and 4.0 mL of hydrochloric acid to a beaker. Add water to make 100.0 mL. Add a plastic-coated stirring bar, insert the electrodes into the solution, and stir for 15 min. Read the potential, in mV. Continue stirring, and at 5-min intervals add 100, 100, 300, and 500 µL of the 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.
Analysis:  Rinse and dry the electrodes, and 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 in the sample taken:
Result = (V × C)/W
V== volume of the Sample solution (mL)
C== determined concentration of fluoride in the Sample solution (µg/mL)
W== nominal weight of calcium carbonate taken (g)
Acceptance criteria:  50 µg/g, with respect to the labeled amount of calcium carbonate
•  Arsenic, Method I 211
Test preparation:  Slowly dissolve a portion of Oral Suspension equivalent to 1.0 g of calcium carbonate in 15 mL of hydrochloric acid. Dilute with water to 55 mL.
Analysis:  Proceed as directed in the chapter, except omit the addition of 20 mL of 7 N sulfuric acid specified under Procedure.
Acceptance criteria:  NMT 3 µg/g, with respect to the labeled amount of calcium carbonate
•  Lead 251
Test preparation:  Mix a portion of Oral Suspension equivalent to 1.0 g of calcium carbonate in 5 mL of water.
Analysis:  To the Test preparation slowly add 8 mL of 3 N hydrochloric acid. Evaporate on a steam bath to dryness, and dissolve the residue in 5 mL of water.
Acceptance criteria:  NMT 3 µg/g, with respect to the labeled amount of calcium carbonate
•  Heavy Metals 231
Test preparation:  Mix a portion of Oral Suspension equivalent to 1.0 g of calcium carbonate with 5 mL of water. Slowly add 8 mL of 3 N hydrochloric acid, and evaporate on a steam bath to dryness. Dissolve the residue in 20 mL of water. Filter, and add water to the filtrate to make 25 mL.
Acceptance criteria:  NMT 20 µg/g, with respect to the labeled amount of calcium carbonate
SPECIFIC TESTS
•  Microbial Enumeration Tests 61 and Tests for Specified Microorganisms 62: The total aerobic microbial count is NMT 102 cfu/mL. It meets the requirements of the tests for absence of Escherichia coli and Pseudomonas aeruginosa.
•  pH 791: 7.5–8.7
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in tight containers, and avoid freezing.
•  USP Reference Standards 11
USP Sodium Fluoride RS
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Natalia Davydova
Scientific Liaison
1-301-816-8328
(DS2010) Monographs - Dietary Supplements
61 Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison
1-301-816-8339
(GCM2010) General Chapters - Microbiology
62 Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison
1-301-816-8339
(GCM2010) General Chapters - Microbiology
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USP35–NF30 Page 2444
Pharmacopeial Forum: Volume No. 27(6) Page 3255