Amoxicillin and Clavulanate Potassium 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

Amoxicillin and Clavulanate Potassium Tablets contain the equivalent of NLT 90.0% and NMT 120.0% of the labeled amounts of amoxicillin (C₁₆H₁₉N₃O₅S) and clavulanic acid (C₈H₉NO₅).

2 IDENTIFICATION

The retention times of the major peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Buffer: 7.8 g of monobasic sodium phosphate in 900 mL of water. Adjust with phosphoric acid or 10 N sodium hydroxide to a pH of 4.4 ± 0.1, and dilute with water to 1000 mL.

Mobile phase: Methanol and Buffer (1:19). Pass through a suitable filter.

Standard solution: 0.5 mg/mL of USP Amoxicillin RS and 0.2 mg/mL of USP Clavulanate Lithium RS in water

Sample stock solution: Dissolve NLT 10 Tablets in water with the aid of mechanical stirring. Transfer to a suitable volumetric ask, and dilute with water to volume.

Sample solution: Dilute a suitable volume of the Sample stock solution with water to obtain a solution containing 0.5 mg/mL of amoxicillin. [Note—Use the Sample solution within 1 h.]

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4-mm × 30-cm; 3- to 10-µm packing L1

Flow rate: 2 mL/min

Injection size: 20 µL

System suitability

Sample: Standard solution

[Note—The relative retention times for clavulanic acid and amoxicillin are 0.5 and 1.0, respectively.]

3.2 Suitability requirements

Resolution: NLT 3.5 between the amoxicillin and clavulanic acid peaks

Tailing factor: NMT 1.5 for each analyte peak

Relative standard deviation: NMT 2.0%

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₁₆H₁₉N₃O₅S in each Tablet taken:

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

r_U = peak response of amoxicillin from the Sample solution

r_S = peak response of amoxicillin from the Standard solution

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

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

P = potency of USP Amoxicillin RS (µg/mg)

F = conversion factor, 0.001 mg/µg

Calculate the percentage of C₈H₉NO₅ in each Tablet taken:

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

U S S U

r_U = peak response of clavulanic acid from the Sample solution

r_S = peak response of clavulanic acid from the Standard solution

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

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

P = potency of clavulanic acid in USP Clavulanate Lithium RS (mg/mg)

Acceptance criteria: 90.0%–120.0%

4 PERFORMANCE TESTS

Disintegration 〈701〉: Tablets labeled for veterinary use only; 30 min, simulated gastric uid TS being substituted for water in the test • Dissolution 〈711〉

[Note—Tablets labeled for veterinary use only are exempt from this requirement.]

Test 1

Medium: Water; 900 mL

Apparatus 2: 75 rpm

Time: 30 min; or 45 min where the Tablets are labeled as chewable

Analysis: Determine the amount of C₁₆H₁₉N₃O₅S and C₈H₉NO₅ dissolved, using the Analysis set forth in the Assay, making any necessary volumetric adjustments.

Tolerances: NLT 85% (Q) of the labeled amount of C₁₆H₁₉N₃O₅S and NLT 80% (Q) of the labeled amount of C H NO are dissolved. 

For Tablets labeled as chewable: NLT 80% (Q) of the labeled amounts of C₁₆H₁₉N₃O₅S and C₈H₉NO₅ is dissolved in 45 min. 

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

Medium, Apparatus 2, and Analysis: Proceed as directed for Test 1.

Times: 45 min for amoxicillin, and 30 min for clavulanic acid

Tolerances: NLT 85% (Q) of the labeled amount of C₁₆H₁₉N₃O₅S and NLT 80% (Q) of the labeled amount of C₈H₉NO₅ are dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 SPECIFIC TESTS

Water Determination, Method I〈921〉:

For products labeled as chewable Tablets: 

For Tablets labeled for veterinary use only: NMT 10.0%

Microbial Enumeration Tests 〈61〉andTests for Specified Microorganisms 〈62〉: The total aerobic microbial count does not exceed 103 cfu/g, and the total combined molds and yeasts count does not exceed 102 cfu/g.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

Labeling: Label chewable Tablets to include the word “chewable” in juxtaposition to the social name. The labeling indicates that chewable Tablets may be chewed before being swallowed or may be swallowed whole. Tablets intended for veterinary use only are so labeled. 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 Amoxicillin RS

USP Clavulanate Lithium RS