Aspirin, Alumina, and Magnesia Tablets

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

Aspirin, Alumina, and Magnesia Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of Aspirin (C₉H₈O₄), the equivalent of NLT 90.0% and NMT 110.0% of the labeled amount of aluminum hydroxide [Al(OH)₃], and NLT 90.0% and NMT 110.0% of the labeled amount of magnesium hydroxide [Mg(OH)₂].

2 IDENTIFICATION

A. The retention time of the aspirin peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay for Aspirin.

B. IDENTIFICATION TESTS GENERAL (191), Magnesium

Sample solution: To a 0.7-g portion of finely powdered Tablets, add 20 mL of 3 N hydrochloric acid and 5 drops of methyl red TS, heat to boiling, and add 6. N ammonium hydroxide until the color of the solution changes to deep yellow. Continue boiling for 2 min, and filter. Use the filtrate for analysis and use the precipitate in Identification C.

Acceptance criteria: Meet the requirements

C. IDENTIFICATION TESTS GENERAL (191), Aluminum

Sample solution: Wash the precipitate obtained in Identification B with a hot solution of ammonium chloride (1 in 50), and dissolve the precipitate in hydrochloric acid.

Acceptance criteria: Meet the requirements

3 ASSAY

3.1 ASPIRIN

Mobile phase: Dissolve 225 mg of tetramethylammonium hydroxide pentahydrate and 200 mg of sodium 1-octanesulfonate in 700 mL of water. Add 150 ml of methanol, 150 mL of acetonitrile, and 1.0 ml of glacial acetic acid, and stir.

Diluent: To 2 g of anhydrous citric acid add 990 mL of acetonitrile, 990 ml. of chloroform, and 20 mL of formic acid, and stir for about 30 min.

Allow to settle, and use the decanted clear solution.

Internal standard solution: 2 mg/mL of phenacetin in Diluent

Salicylic acid stock solution: 1 mg/mL of USP Salicylic Acid RS in Diluent

Standard solution: 6.5 mg/mL of USP Aspirin RS and 0.2 mg/mL each of USP Salicylic Acid RS and phenacetin prepared as follows. Transfer, accurately weighed, about 325 mg of USP Aspirin RS to a 50-ml volumetric flask. Add 10.0 mL of Salicylic acid stock solution and 5.0 mL of Internal standard solution, dilute with Diluent to volume, and mix.

Sample solution: Nominally 6.5 mg/mL of aspirin prepared as follows. Transfer a quantity equivalent to about 325 mg of aspirin from NLT 20 finely powdered Tablets to a screw-capped, 120-mL bottle. Add 5.0 mL of Internal standard solution and 45.0 mL of Diluent, mix, and sonicate for 2-5 min. Centrifuge, and use the resultant clear solution.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 4-mm x 30-cm; 10-µm packing 11

Flow rate: 2 mL/min

Injection volume: 5 µL

System suitability

Sample: Standard solution

[NOTE-The relative retention times for salicylic acid, aspirin, and phenacetin are about 0.3, 0.6, and 1.0, respectively. Record each chromatogram until the chloroform peak appears at the relative retention time of about 1.8.]

Suitability requirements

Resolution: NLT 2.0 between two adjacent peaks for salicylic acid, aspirin, and phenacetin

Tailing factor: NMT 2.0 for each peak.

Relative standard deviation: NMT 3.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of aspirin (C₉H₈O₄) in the portion of Tablets taken:

Result = (R_u /R_s ) × (C_s /C_u ) × 100

R_u = peak response ratio of aspirin to phenacetin from the Sample solution

R_s = peak response ratio of aspirin to phenacetin from the Standard solution

C_s = concentration of USP Aspirin RS in the Standard solution (mg/mL)

C_u = nominal concentration of aspirin in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

3.2 ALUMINUM HYDROXIDE

Sample solution: Nominally 1.25 mg/mL of aluminum hydroxide prepared as follows. To a portion of NLT 20 powdered Tablets, equivalent to 250 mg of aluminum hydroxide in a 150-mL beaker, add 20 ml of water, stir, and slowly add 30 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, dilute with water to volume, and mix.

Titrimetric system

Mode: Residual titration

Titrant: 0.05 M edetate disodium VS

Back titrant: 0.05 M zinc sulfate VS

Blank: Water, 50 mL

Endpoint detection: Visual

Analysis: To 50 mL of Sample solution add, in the order named and with continuous stirring, 25.0 mL of the 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. Titrate with Back titrant until the color changes from green-violet to rose-pink. Perform a blank determination, substituting 50 mL of water for the Sample solution, and make any necessary corrections. Each mL of Titrant consumed is equivalent to 3.900 mg of aluminum hydroxide [Al(OH)₃].

Acceptance criteria: 90.0%-110.0%

3.3 MAGNESIUM HYDROXIDE

Indicator solution: Dissolve by mixing 200 mg of eriochrome black T in a mixture of 15 mL of triethanolamine and 5 mL of dehydrated alcohol.

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

Titrimetric system

Mode: Direct titration

Titrant: 0.05 M edetate disodium VS

Blank: Water, 50 mL

Endpoint detection: Visual

Analysis: To a volume of Sample solution, equivalent to 80 mg of magnesium hydroxide, add 200 mL of water, 20 mL of triethanolamine, 50 mL of ammonia-ammonium chloride buffer TS, and 2 drops of Indicator solution. Cool the solution to between 3º and 4º by immersion in an ice bath, then remove, and titrate with Titrant until the color changes to pure blue. Perform a blank determination, substituting for the Sample solution a volume of water equal to the volume of Sample solution used, and make any necessary corrections. Each mL of Titrant is equivalent to 2.916 mg of magnesium hydroxide [Mg(OH)₂].

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

DISSOLUTION (711)

Medium: 0.05 M acetate buffer, prepared by mixing 2.99 g of sodium acetate (trihydrate) and 1.66 mL of glacial acetic acid with water to obtain 1000 mL of solution with a pH of 4.50 ± 0.05; 900 mL

Apparatus 2: 75 rpm

Time: 45 min

Standard solution: A known concentration of USP Aspirin RS in Medium. Prepare the Standard solution at the time of use. [NOTE-A quantity of methanol NMT 1% of the total volume of the Standard solution may be used to dissolve the Reference Standard into solution prior to dilution with Medium.]

Sample solution: Pass a portion of the solution under test through a suitable filter, and dilute with Medium, if necessary.

Instrumental conditions

Mode: UV

Analytical wavelength: 265 nm

Analysis

Samples: Standard solution and Sample solution

Determine the percentage of the labeled amount of aspirin (C₉H₈O₄) dissolved from UV absorbances at the isosbestic point of aspirin and

salicylic acid at about 265 nm.

Tolerances: NLT 75% (Q) of the labeled amount of aspirin (C₉H₈O₄) is dissolved.

UNIFORMITY OF DOSAGE UNITS (905), Weight VariationandContent Uniformity: Meet the requirements for weight variation with respect to aluminum

hydroxide and to magnesium hydroxide. Meet the requirements for content uniformity with respect to aspirin.

5 IMPURITIES

LIMIT OF FREE SALICYLIC ACID

Mobile phase, Diluent, Internal standard solution, Salicylic acid stock solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay for Aspirin.

System suitability solution: Transfer about 325 mg of USP Aspirin RS to a 50-mL volumetric flask. Add 10.0 mL of Salicylic acid stock solution and 5.0 mL of Internal standard solution, dilute with Diluent to volume, and mix.

Standard solution: 0.2 mg/mL of USP Salicylic Acid RS prepared as follows. Transfer 10.0 ml of Salicylic acid stock solution and 5.0 mL of Internal standard solution to a 50-mL volumetric flask, dilute with Diluent to volume, and mix.

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for salicylic acid, aspirin, and phenacetin are about 0.3, 0.6, and 1.0, respectively. Record each chromatogram until the chloroform peak appears at the relative retention time of about 1.8.]

Suitability requirements

Resolution: NLT 2.0 between two adjacent peaks for salicylic acid, aspirin, and phenacetin, System suitability solution

Tailing factor: NMT 2.0, System suitability solution

Relative standard deviation: NMT 3.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of salicylic acid in the portion of Tablets taken:

Result = (R_u /R_s ) × (C_s /C_u ) × 100

R_u =  peak response ratio of salicylic acid to phenacetin from the Sample solution

R_s = peak response ratio of salicylic acid to phenacetin from the Standard solution

C_s = concentration of USP Salicylic Acid RS in the Standard solution (mg/mL)

C_u = nominal concentration of aspirin in the Sample solution (mg/mL)

Acceptance criteria: NMT 3.0%

6 SPECIFIC TESTS

Acid-Neutralizing Capacity 〈301〉: NLT 1.9 mEq of acid is consumed for each 325 mg of aspirin in the Tablets.

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Aspirin RS

USP Salicylic Acid RS