Theophylline Compounded 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

Theophylline Compounded Oral Suspension contains NLT 90.0% and NMT 110.0% of the labeled amount of theophylline (C₇H₈N₄O₂ ).

Prepare Theophylline Compounded Oral Suspension 5 mg/mL as follows (see Pharmaceutical Compounding—Nonsterile Preparations 〈795〉).

Calculate the required quantity of each ingredient for the total amount to be prepared. Calculate the amount of Theophylline on the anhydrous basis. If using tablets, place the required number in a suitable mortar, and comminute to a fine powder, or use Theophylline powder. Add about 20 mL of the Vehicle in small portions, and triturate to make a smooth paste. Add increasing volumes of the Vehicle to make a liquid that is pourable. Transfer the contents of the mortar, stepwise and quantitatively, to a calibrated container. Add enough of the liquid Vehicle to bring to final volume, and mix well.

2 ASSAY

2.1 Procedure

Solution A: Dissolve 2.500 g of sodium citrate and 1.633 g of citric acid (anhydrous) in 850 mL of ASTM Type I water, add 150 mL of methanol, and pass through 0.45-μm membrane filters.

Solution B: Acetonitrile

Mobile phase: See Table 1. Make adjustments, if necessary.

Table 1

Diluent: Solution A

System suitability solution: 0.10 mg/mL of USP Theophylline RS and 0.20 mg/mL of USP Caffeine RS in Solution A

Standard solution: 0.10 mg/mL of USP Theophylline RS in Solution A

Sample solution: 0.10 mg/mL of theophylline prepared from Oral Suspension and Solution A

2.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Flow rate: 1.5 mL/min

Injection volume: 20 μL

2.3 System suitability

Sample: System suitability solution

2.4 Suitability requirements

Resolution: NLT 3.0 between the theophylline and caffeine peaks

Column efficiency: NLT 1000 theoretical plates for the theophylline peak

Tailing factor: NMT 1.5 for the theophylline peak

Relative standard deviation: NMT 2.0% for replicate injections

2.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of theophylline (C₇H₈N₄O₂ ) in the portion of Oral Suspension taken:

Result = (r_U/r_S ) × (C_S /C_U ) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

3 SPECIFIC TESTS

pH 〈791〉: 4.0–5.0

4 ADDITIONAL REQUIREMENTS

Packaging and Storage: Package in tight, light-resistant containers. Store at controlled room temperature. Do not refrigerate.

Beyond-Use Date: NMT 90 days after the date on which it was compounded when stored at controlled room temperature

Labeling: Label to state that it is to be well shaken before use, protected from light, not to be refrigerated, and to state the Beyond-Use Date.

USP Reference Standards 〈11〉

USP Caffeine RS

USP Theophylline RS