Aminophylline Rectal 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

Aminophylline Rectal Solution is an aqueous solution of Aminophylline, prepared with the aid of Ethylenediamine. It contains an amount of aminophylline equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of anhydrous Theophylline (C₇H₈N₄O₂).

Rectal Solution may contain an excess of ethylenediamine, but no other substance may be added for the purpose of pH adjustment.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

Sample: Dilute an amount of Rectal Solution, equivalent to 500 mg of aminophylline, with water to 20 mL. Add, with constant stirring, 1 mL of 3 N hydrochloric acid or enough to precipitate the theophylline completely, and filter (save the filtrate). Wash the precipitate with a small portion of cold water until free from chloride, and dry at 105° for 4 h.

Acceptance criteria: The dried precipitate meets the requirements.

B.

Analysis: To the filtrate obtained in Identification test A add 0.5 mL of benzenesulfonyl chloride and 5 mL of 1 N sodium hydroxide to render alkaline, shake by mechanical means for 10 min, and add 5 mL of 3 N hydrochloric acid to acidify. Chill, collect the precipitated disulfonamide of ethylenediamine, and wash with water. Recrystallize the washed precipitate from water, and dry at 105° for 1 h. Acceptance criteria: The dried precipitate melts at 164°–171°.

3 ASSAY

Procedure

Standard solution: 8 µg/mL of USP Theophylline RS in dilute hydrochloric acid (1:100)

Sample solution: Pipet a volume of Rectal Solution equivalent to 500 mg of aminophylline into a 500-mL volumetric ask, and dilute with water to volume. Pipet 5 mL of this solution to a second 500-mL volumetric ask, add 50-mL of dilute hydrochloric acid (1:10), and dilute with water to volume.

Instrumental conditions

Mode: UV

Analytical wavelength: About 270 nm

Cell: 1 cm

Blank: Dilute hydrochloric acid (1:100)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of anhydrous theophylline (C₇H₈N₄O₂) in the portion of Rectal Solution taken:

Result = (A_U /A_S ) × (C_S /C_U) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Theophylline RS in the Standard solution (µg/mL)

C_U = nominal concentration of theophylline in the Sample solution (µg/mL)

Acceptance criteria: 90.0%–110.0%

4 OTHER COMPONENTS

Content of Ethylenediamine

Sample solution: Measure a volume of Rectal Solution, equivalent to 500 mg of aminophylline, and dilute with water if necessary to make 30 mL.

Titrimetric system

Mode: Direct titration

Titrant: 0.1 N hydrochloric acid VS

Endpoint detection: Visual

Analysis: Add methyl orange TS to the Sample solution, and titrate. Each mL of 0.1 N hydrochloric acid is equivalent to 3.005 mg of ethylene diamine (C₂H₈N₂).

Acceptance criteria: 218–267 mg of ethylenediamine (C₂H₈N₂) per g of theophylline (C₇H₈N₄O₂) found in the Assay

5 SPECIFIC TESTS

pH 〈791〉: 9.0–9.5

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, single-dose or multiple-dose containers at controlled room temperature.

Labeling: Label the Rectal Solution to state the content of anhydrous theophylline.

USP Reference Standards 〈11〉

USP Theophylline RS