Aluminum Chlorohydrate Solution

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

Aluminum Chlorohydrate Solution consists of complex basic aluminum chloride that is polymeric and encompasses a range of aluminum-to chloride ratios between 1.91:1 and 2.10:1. The following solvents may be used: water, propylene glycol, dipropylene glycol, or alcohol. It contains the equivalent of NLT 90.0% and NMT 110.0% of the labeled concentration of anhydrous aluminum chlorohydrate (AI_y(OH)_3y-zCl_z).

2 IDENTIFICATION

A. Identification Tests—General, Aluminum〈191〉andChloride〈191〉

Sample solution: Nominally equivalent to 100 mg/mL of anhydrous aluminum chlorohydrate

Acceptance criteria: Meets the requirements

B. Identification of Propylene Glycol

Perform this test where propylene glycol is stated on the label.

Sample solution: 2 g of Solution in 10 mL of isopropyl alcohol. Mix, filter, and evaporate the  filtrate to 1 mL on a steam bath. Acceptance criteria: The IR spectrum of a lm of the Sample solution on a silver chloride disk exhibits maxima only at the same wavelengthsas that of a similar preparation of a lm of propylene glycol.

C. Identification of Dipropylene Glycol

Perform this test where dipropylene glycol is stated on the label.

Sample solution: 2 g of Solution in 10 mL of isopropyl alcohol. Mix, filter, and evaporate the  filtrate to 1 mL on a steam bath. Acceptance criteria: The IR spectrum of a lm of the Sample solution on a silver chloride disk exhibits maxima only at the same wavelengths as that of a similar preparation of a lm of dipropylene glycol.

D. Identification of Alcohol

Perform this test where alcohol is stated on the label.

Analysis: Mix 5 drops of Solution in a small beaker with 1 mL of potassium permanganate solution (1 in 100) and 5 drops of 2 N sulfuric acid, and cover the beaker immediately with filter paper moistened with a freshly prepared solution of 0.1 g of sodium nitroferricyanide and 0.25 g of Piperazine in 5 mL of water.

Acceptance criteria: An intense blue color is produced on the filter paper, the color becoming paler after a few min.

2.1 ASSAY

2.2 Procedure 1: Content of Chloride

Sample: 1.4 g of Solution

Titrimetric system

Mode: Direct titration

Titrant: 0.1 N silver nitrate VS

Electrode system: A silver–silver chloride glass electrode and a silver billet electrode system

Endpoint detection: Potentiometric

Analysis: Transfer the Sample to a 250-mL beaker, and add 100 mL of water and 10 mL of diluted nitric acid with stirring. Titrate with Titrant, and determine the endpoint.

Acceptance criteria: Each mL of 0.1 N silver nitrate is equivalent to 3.545 mg of chloride (Cl). Use the chloride content thus obtained to calculate the aluminum/chloride atomic ratio.

2.3 Procedure 2: Content of Aluminum

Edetate disodium titrant: Prepare and standardize as directed in Reagents, Volumetric Solutions, Edetate Disodium, Twentieth-Molar (0.05 M), except use 37.2 g of edetate disodium.

Sample solution: Transfer 400 mg of Solution to a 250-mL beaker, add 20 mL of water and 5 mL of hydrochloric acid, boil on a hot plate for NLT 5 min, and allow to cool.

Titrimetric system

Mode: Back titration

Titrant: 0.1 M zinc sulfate VS

Endpoint detection: Visual

Analysis: To the Sample solution add 25.0 mL of Edetate disodium titrant, and adjust with 2.5 N ammonium hydroxide or 1 N acetic acid to a pH of 4.7 ± 0.1. Add 20 mL of acetic acid–ammonium acetate buffer TS, 50 mL of alcohol, and 5 mL of dithizone TS. The pH of this solution should be 4.7 ± 0.1. Titrate excess edetate disodium with Titrant until the color changes from green-violet to rose-pink. Perform a blank titration, and make any necessary correction.

Acceptance criteria: Each mL of 0.1 M Edetate disodium titrant consumed is equivalent to 2.698 mg of aluminum (Al). Use the aluminum content thus obtained to calculate the aluminum/chloride atomic ratio. 

2.4 Procedure 3: Aluminum/Chloride Atomic Ratio 

Analysis: Use the percentage of aluminum found in Content of Aluminum and the percentage of chloride found in Content of Chloride. Calculate the aluminum/chloride atomic ratio (X) as follows: 

Result = (P_Al/P_Cl) × (A_Cl /A_Al) 

Al Cl Cl Al 

P_Al = percentage of aluminum found in Content of Aluminum 

P_Cl = percentage of chloride found in Content of Chloride  

A_Cl = atomic weight of chlorine (Cl), 35.453 

A_Al = atomic weight of aluminum (Al), 26.98 

Acceptance criteria: 1.91:1 to 2.10:1 

3 Procedure 4 

Analysis: Calculate the percentage of the labeled concentration of anhydrous aluminum chlorohydrate (AI_y(OH)_3y-zCl_z) in the portion of Solution taken: 

Result = P_Al × {[A_AlX + (M(3X − 1)) + A_Cl ]/A_AlX}  

P_Al= percentage of aluminum found in Content of Aluminum 

A_Al = atomic weight of aluminum (Al), 26.98

X = aluminum/chloride atomic ratio, as determined in Aluminum/Chloride Atomic Ratio

M = molecular weight of the hydroxide anion (OH), 17.01

A_Cl = atomic weight of chlorine (Cl), 35.453

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

Change to read:

Arsenic 〈211〉, Procedures, Procedure 1 (CN 1-Jun-2023) : NMT 2 ppm

Change to read:

Limit of Iron

Standard preparation: 2.0 mL of Standard Iron Solution, prepared as directed in Iron 〈241〉, Procedures, Procedure 1 (CN 1-Jun-2023) Test preparation: Transfer 5.3 g of Solution to a 100-mL volumetric ask, and dilute with water to volume.

Analysis: Transfer 2.0 mL of the Standard preparation into a 50-mL beaker. Transfer 5.0 mL of the Test preparation into a second 50-mL beaker. To each of the beakers add 5 mL of 6 N nitric acid, cover with a watch glass, and boil on a hot plate for 3–5 min. Allow to cool. Add 5 mL of Ammonium Thiocyanate Solution, prepared as directed in Iron 〈241〉, Procedures, Procedure 1 (CN 1-Jun-2023) , transfer to separate 50-mL color-comparison tubes, and dilute with water to volume.

Acceptance criteria: 75 ppm; the color of the solution from the Test preparation is not darker than that from the Standard preparation.

5 SPECIFIC TESTS

pH 〈791〉

Sample solution: Dilute 3 g of Solution with water to 10 mL.

Acceptance criteria: 3.0–5.0

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers.

Labeling: Label Solution to state the solvent used and the claimed concentration of anhydrous aluminum chlorohydrate contained therein.