Alumina, Magnesia, and Calcium Carbonate Oral Suspension

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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1 DEFINITION

Alumina, Magnesia, and Calcium Carbonate Oral Suspension contains NLT 90.0% and NMT 110.0% of the labeled amounts of aluminum hydroxide [Al(OH)₃], magnesium hydroxide [Mg(OH)₂], and calcium carbonate (CaCO₃).

2 IDENTIFICATION

A. Identification Tests-General, Calcium〈191〉

Sample solution: To 5 g of Oral Suspension add 25 mL of 2 N sulfuric acid, stir, and allow to stand for 5 min. Add 25 mL of alcohol, stir, and place in an ice bath for 30 min. Filter while cold, retaining the filtrate for Identification test B. Wash the precipitate with 50 mL of 0.75 N sulfuric acid, and discard the washings. Dissolve the precipitate in 3 N hydrochloric acid, filter, and use the filtrate.

Acceptance criteria: Meets the requirements

B. Identification Tests-General, Aluminum〈191〉

Sample solution: To the

ltrate obtained in Identification test A, add 5 drops of methyl red TS, and heat to boiling. Add 6 N ammonium hydroxide until the color of the solution changes to deep yellow, continue boiling for 2 min, and filter through hardened filter paper. (Retain the filtrate for Identification test C.) Wash the precipitate with 350 mL of a hot solution containing 20 mg/mL of ammonium chloride, discarding the washings. Dissolve the precipitate so obtained in 3 N hydrochloric acid.

Acceptance criteria: Meets the requirements

C. Identification Tests-General, Magnesium〈191〉

Sample solution: The filtrate obtained in Identification test B.

Acceptance criteria: Meets the requirements

3 ASSAY

3.1 Aluminum Hydroxide

Edetate disodium titrant: Prepare and standardize as directed in Reagents, Volumetric Solutions, Edetate Disodium, Twentieth-Molar (0.05 M).

Sample solution: Transfer an amount of Oral Suspension, previously shaken in its original container, equivalent to 600 mg of aluminum hydroxide, to a tared beaker, and weigh. Add 20 mL of water, stir, and slowly add 40 mL of 3 N hydrochloric acid. Heat gently, if necessary, to aid solution, cool, and transfer to a 200-mL volumetric flask. Wash the beaker with water, adding the washings to the flask, and add water to volume.

Analysis: Pipet 10 mL of the Sample solution into a 250-mL beaker, add 20 mL of water, then add, in the order named and with continuous

stirring, 25.0 mL of Edetate disodium titrant and 20 mL of acetic acid–ammonium acetate buffer TS, and heat the solution near the boiling temperature for 5 min. Cool, and add 50 mL of alcohol and 2 mL of dithizone TS, and mix. Titrate the excess edetate disodium with 0.05 M zinc sulfate VS until the color changes from green-violet to rose-pink. Perform a blank determination, substituting 10 mL of water for the

Sample solution, and make any necessary correction. Each mL of Edetate disodium titrant consumed is equivalent to 3.900 mg of aluminum hydroxide [Al(OH)₃].

Acceptance criteria: 90.0%–110.0%

3.2 Magnesium Hydroxide

Sample solution: Prepare as directed in the Assay for Aluminum Hydroxide.

Analysis: Pipet a volume of the Sample solution, equivalent to 40 mg of magnesium hydroxide, into a 400-mL beaker, add 200 mL of water and 20 mL of trolamine, and mix. Add 50 mL of ammonia–ammonium chloride buffer TS and 2 drops of an eriochrome black indicator solution (prepared by dissolving 200 mg of eriochrome black T in a mixture of 15 mL of trolamine and 5 mL of dehydrated alcohol, and mixing). Cool the solution to between 3° and 4° by immersing the beaker in an ice bath, and titrate with 0.05 M edetate disodium VS until the color changes to pure blue. Perform a blank determination, substituting 10 mL of water for the Sample solution, and make any necessary correction. From the volume of 0.05 M edetate disodium consumed, subtract the volume of 0.05 M edetate disodium consumed in the Assay for Calcium Carbonate. Each mL of 0.05 M edetate disodium is equivalent to 2.916 mg of magnesium hydroxide [Mg(OH) ].

Acceptance criteria: 90.0%–110.0%

3.3 Calcium Carbonate

Sample solution: Prepare as directed in the Assay for Aluminum Hydroxide.

Analysis: Pipet a volume of the Sample solution, equivalent to 50 mg of calcium carbonate, into a 400-mL beaker, and add 200 mL of water, 5mL of sodium hydroxide solution (1 in 2), and 250 mg of hydroxy naphthol blue. Stir with a magnetic stirrer, and titrate immediately with 0.05 M edetate disodium VS until the solution is distinctly blue. Each mL of 0.05 M edetate disodium is equivalent to 5.004 mg of calcium carbonate (CaCO₃).

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

4.1 Chloride and Sulfate, Chloride〈221〉

Sample solution: Dissolve 5.0 g in 3 mL of nitric acid, add water to make 100 mL, and filter.

Acceptance criteria: NMT 0.14%; a 10.0-mL portion of the Sample solution shows no more chloride than corresponds to 1.0 mL of 0.020 N hydrochloric acid.

4.2 Chloride and Sulfate, Sulfate〈221〉

Sample solution: Dissolve 5.0 g in 7 mL of 3 N hydrochloric acid, and gently heat. Cool, add water to make 250 mL, and filter.

Acceptance criteria: NMT 0.1%; a 20.0-mL portion of the Sample solution shows no more sulfate than corresponds to 0.40 mL of 0.020 N sulfuric acid.

Change to read:

4.3 Arsenic 〈211〉, Procedures, Procedure 1 (CN 1-Jun-2023)

Standard preparation: Prepare as directed in Arsenic 〈211〉, Procedures, Procedure 1 (CN 1-Jun-2023) , except prepare it to contain 5 μg of arsenic instead of 3 μg.

Test preparation: Dissolve a portion of Oral Suspension, equivalent to 0.5 g of aluminum hydroxide [Al(OH)₃], in 20 mL of 7 N sulfuric acid.

Acceptance criteria: NMT 10 ppm, based on the aluminum hydroxide [Al(OH) ] content

5 SPECIFIC TESTS

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: Its total aerobic microbial count does not exceed 102 cfu/mL, and it meets the requirements of the test for the absence of Escherichia coli.

pH 〈791〉: 7.5–8.5

Acid-Neutralizing Capacity 〈301〉

Acceptance criteria: The acid consumed by the minimum single dose recommended in the labeling is NLT 5 mEq, and NLT the number ofmEq calculated by the formula:

Result = 0.55 × (F_A× A) + 0.8 × (F_M× M) + 0.9 × (F_C× C)

F_A = theoretical acid-neutralizing capacity of aluminum hydroxide [Al(OH)₃], 0.0385 mEq

A = amount of aluminum hydroxide [Al(OH)₃] in the specimen tested, based on the labeled quantity (mg)

F_M = theoretical acid-neutralizing capacity of magnesium hydroxide [Mg(OH)₂], 0.0343 mEq

M = amount of magnesium hydroxide [Mg(OH)₂] in the specimen tested, based on the labeled quantity (mg)

F_C = theoretical acid-neutralizing capacity of calcium carbonate (CaCO₃), 0.02 mEq

C = amount of calcium carbonate (CaCO₃) in the specimen tested, based on the labeled quantity (mg)

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and avoid freezing.

Labeling: Oral Suspension may be labeled to state the aluminum hydroxide content in terms of the equivalent amount of dried aluminum hydroxide gel, on the basis that each mg of dried gel is equivalent to 0.765 mg of aluminum hydroxide [Al(OH)₃].