Propranolol Hydrochloride 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

Propranolol Hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of propranolol hydrochloride (C₁₆H₂₁NO₂ · HCl).

2 IDENTIFICATION

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

Add the following:

▲B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.▲ (USP 1-Aug-2021)

3 ASSAY

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Procedure

▲Mobile phase: Dissolve 1.6 g of sodium dodecyl sulfate and 0.31 g of tetrabutylammonium phosphate in a mixture of 1 mL of sulfuric acid, 450 mL of water, and 550 mL of acetonitrile. Adjust with 2 N sodium hydroxide solution to a pH of 3.3.

Standard solution: 0.2 mg/mL of USP Propranolol Hydrochloride RS in Mobile phase. Sonication may be needed to aid dissolution.

Sample stock solution: Nominally 1.0 mg/mL of propranolol hydrochloride in Mobile phase prepared as follows. Transfer a suitable amount of powdered Tablets (NLT 20) to a suitable volumetric flask, and add Mobile phase to 60% of the flask volume. Sonicate and dilute with Mobile phase to volume. Centrifuge a portion for 10 min, and pass the solution through a suitable filter of 0.45-µm pore size.

Sample solution: Nominally 0.2 mg/mL of propranolol hydrochloride in Mobile phase from Sample stock solution▲

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 292 nm. For Identification B, use a diode array detector in the range of 200–400 nm.

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

Flow rate: 1.8 mL/min

Injection volume: 20 µL

Run time: NLT 11 times the retention time of propranolol

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of propranolol hydrochloride (C₁₆H₂₁NO₂ · HCl) in the portion of Tablets taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of propranolol from the Sample solution

rₛ = peak response of propranolol from the Standard solution

Cₛ = concentration of USP Propranolol Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of propranolol hydrochloride in the Sample solution (mg/mL)

▲ (USP 1-Aug-2021)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

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Dissolution 〈711〉

Medium: Dilute hydrochloric acid (1 in 100); 1000 mL

Apparatus 1: 100 rpm

Time: 30 min

Standard solution: USP Propranolol Hydrochloride RS at a known concentration in Medium

Sample solution: Filtered portions of the solution under test. Dilute with Medium as needed.

Instrumental conditions

Mode: UV

Analytical wavelength: Maximum absorbance at about 289 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of propranolol hydrochloride (C₁₆H₂₁NO₂ · HCl) dissolved:

▲Result = (Aᵤ / Aₛ) × Cₛ × D × V × (1/L) × 100

Aᵤ = absorbance of the Sample solution

Aₛ = absorbance of the Standard solution

Cₛ = concentration of USP Propranolol Hydrochloride RS in the Standard solution (mg/mL)

D = dilution factor for the Sample solution

V = volume of Medium, 1000 mL

L = label claim (mg/Tablet)▲

▲ (USP 1-Aug-2021)

Tolerances: NLT 75% (Q) of the labeled amount of propranolol hydrochloride (C₁₆H₂₁NO₂ · HCl) is dissolved.

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Uniformity of Dosage Units 〈905〉: Meet the requirements

▲ (USP 1-Aug-2021)

5 IMPURITIES

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Organic Impurities

Mobile phase and Chromatographic system: Proceed as directed in the Assay.

System suitability solution:

0.002 mg/mL of USP Propranolol Related Compound A RS and

2 mg/mL of USP Propranolol Hydrochloride RS

in Mobile phase

Standard solution:

0.004 mg/mL of USP Propranolol Hydrochloride RS in Mobile phase

Sensitivity solution:

0.001 mg/mL of USP Propranolol Hydrochloride RS in Mobile phase from Standard solution

Sample solution:

Nominally 2 mg/mL of propranolol hydrochloride in Mobile phase prepared as follows. Transfer a suitable amount of powdered Tablets (NLT 20) to a suitable volumetric flask, and add Mobile phase to 60% of the flask volume. Sonicate and dilute with Mobile phase to volume. Centrifuge a portion of the solution for 10 min, and pass the solution through a suitable filter of 0.45-µm pore size.

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

[Note—The relative retention times for propranolol related compound A and propranolol are 0.6 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 3.0 between propranolol and propranolol related compound A, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each specified or any unspecified impurity in the portion of Tablets taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × (1/F) × 100

rᵤ = peak response of any specified or unspecified impurity from the Sample solution

rₛ = peak response of propranolol from the Standard solution

Cₛ = concentration of USP Propranolol Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of propranolol hydrochloride in the Sample solution (mg/mL)

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

a 3,3′-(Isopropylazanediyl)bis[1-(naphthalen-1-yloxy)propan-2-ol].

b 1,3-Bis(naphthalen-1-yloxy)propan-2-ol.

▲ (USP 1-Aug-2021)

6 ADDITIONAL REQUIREMENTS

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Packaging and Storage: Preserve in well-closed, light-resistant containers. ▲Store at controlled room temperature.▲ (USP 1-Aug-2021)

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USP Reference Standards 〈11〉

USP Propranolol Hydrochloride RS

▲USP Propranolol Related Compound A RS

3-(Naphthalen-1-yloxy)propane-1,2-diol.

C₁₃H₁₄O₃ 218.25▲ (USP 1-Aug-2021)