Benzonatate Capsules

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

Benzonatate Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of benzonatate [C₃₀H₅₃NO₁₁ (av.)].

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197F

Sample: The contents of Capsules

Acceptance criteria: Meets the requirements. If a difference is observed, or if excipients are present, use an amount of the contents of Capsules equivalent to about 100 mg of benzonatate. Mix with 25 mL of 0.01 N hydrochloric acid, and proceed as directed in Identification—Organic Nitrogenous Bases 〈181〉, beginning with “Transfer the liquid to a separator”.

B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U

Sample solution: Nominally 15 μg/mL of benzonatate from the contents of Capsules

Acceptance criteria: Meets the requirements

3 ASSAY

Procedure

Standard solution: 500 μg/mL of USP Benzonatate RS

Sample stock solution: Nominally 5 mg/mL of benzonatate in chloroform, prepared as follows. Mix a number of Capsules, equivalent to about 500 mg of benzonatate, with 40 mL of chloroform in a suitable high-speed blender, and dilute with chloroform to 100.0 mL.

Sample solution: Nominally 500 μg/mL of benzonatate prepared as follows. Transfer 10.0 mL of Sample stock solution into a 100-mL volumetric flask. Evaporate the chloroform on a steam bath with the aid of a current of air. Dissolve the residue in water and dilute with water to volume.

Instrumental conditions

Mode: Vis

Analytical wavelength: 500 nm

Cell: 1 cm

Blank: Water

Analysis

Samples: Standard solution, Sample solution, and Blank

Transfer 4.0 mL each of the Standard solution, Sample solution, and Blank to separate test tubes. To each tube add in succession 1.0 mL of 1 M hydroxylamine hydrochloride and 1.0 mL of 3.5 N sodium hydroxide, mixing after each addition. Allow to stand for 10 min, accurately timed, then add 1.0 mL of 3.5 N hydrochloric acid, mix, add 1.0 mL of an 80-mg/mL ferric chloride solution, and mix. Allow to stand for 30 min, accurately timed. Gently swirl the tubes for 1 min to remove any gas bubbles present, then concomitantly determine the absorbances of the solutions.

Calculate the percentage of the labeled amount of benzonatate [C₃₀H₅₃NO₁₁ (av.)] in the Capsules taken:

Result = (Aᵤ/Aₛ) × (Cₛ/Cᵤ) × 100

Aᵤ = absorbance of the Sample solution

Aₛ = absorbance of the Standard solution

Cₛ = concentration of USP Benzonatate RS in the Standard solution (μg/mL)

Cᵤ = nominal concentration of benzonatate in the Sample solution (μg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Test 1

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Mobile phase: Acetonitrile and 0.04 M monobasic potassium phosphate (75:25)

Standard solution: 0.1 mg/mL of USP Benzonatate RS. Sonicate to dissolve, if needed.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size.

Chromatographic system

Mode: LC

Detector: UV 310 nm

Column: 3.9-mm × 30-cm; packing L1

Flow rate: 1.5 mL/min

Injection volume: 15 μL

System suitability

Sample: Standard solution

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of benzonatate [C₃₀H₅₃NO₁₁ (av.)] dissolved:

Result = (rᵤ/rₛ) × Cₛ × V × 1/L × 100

rᵤ = peak response of benzonatate from the Sample solution

rₛ = peak response of benzonatate from the Standard solution

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

V = volume of Medium, 900 mL

L = label claim (mg/Capsule)

Tolerances: NLT 80% (Q) of the labeled amount of benzonatate [C₃₀H₅₃NO₁₁ (av.)] is dissolved

Test 2

If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Tier 1

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Time: 45 min

Standard solution: 0.022 mg/mL of USP Benzonatate RS in Medium. Sonicate to dissolve, if needed.

Sample solution: Withdraw a portion of the solution under test, dilute with Medium to a concentration of about 0.022 mg/mL, and pass through a suitable filter of 0.45-μm or finer pore size.

Instrumental conditions

Mode: UV

Analytical wavelength: 310 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of benzonatate [C₃₀H₅₃NO₁₁ (av.)] dissolved:

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

Aᵤ = absorbance of the Sample solution

Aₛ = absorbance of the Standard solution

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

V = volume of Medium, 900 mL

D = dilution factor for the Sample solution

L = label claim (mg/Capsule)

Tolerances: NLT 75% (Q) of the labeled amount of benzonatate [C₃₀H₅₃NO₁₁ (av.)] is dissolved. If this tolerance cannot be met because of the presence of cross-linking in the gelatin Capsules, proceed to Tier 2.

Tier 2 (only if Tolerances in Tier 1 cannot be met because of the presence of cross-linking in the gelatin Capsules)

Medium: Simulated gastric fluid; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Solution A: Dissolve about 5.44 g of monobasic potassium phosphate in 1000 mL of water.

Mobile phase: Acetonitrile and Solution A (75:25)

Standard solution: 0.022 mg/mL of USP Benzonatate RS in Medium. Sonicate to dissolve, if needed.

Sample solution: Withdraw a portion of the solution under test, dilute with Medium to a concentration of about 0.022 mg/mL, and pass through a suitable filter of 0.45-μm or finer pore size.

Chromatographic system

Mode: UV

Detector: UV 310 nm

Guard column: 4.0-mm × 4.0-mm; 5-μm packing L1

Analytical column: 4.0-mm × 25-cm; 7-μm packing L1

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 20 μL

System suitability

Sample: Standard solution

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of benzonatate [C₃₀H₅₃NO₁₁ (av.)] dissolved:

Result = (rᵤ/rₛ) × Cₛ × V × D × 1/L × 100

rᵤ = peak response of benzonatate from the Sample solution

rₛ = peak response of benzonatate from the Standard solution

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

V = volume of Medium, 900 mL

D = dilution factor for the Sample solution

L = label claim (mg/Capsule)

Tolerances: NLT 75% (Q) of the labeled amount of benzonatate [C₃₀H₅₃NO₁₁ (av.)] is dissolved.

UNIFORMITY OF DOSAGE UNITS 〈905〉

Meet the requirements.

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.

USP Reference standards 〈11〉:

USP Benzonatate RS