Amoxicillin and Clavulanate Potassium Tablets
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).
IDENTIFICATION
• The retention times of the major peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.
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 flask, and dilute with water to volume.
Sample solution:
Dilute a suitable volume of the Sample stock solution filtrate with water to obtain a solution containing 0.5 mg/mL of amoxicillin. [Note—Use the Sample solution within 1 h. ]
Chromatographic system
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. ]
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%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C16H19N3O5S in each Tablet taken:
Result = (rU/rS) × (CS/CU) × P × F × 100
| rU | = | = peak response of amoxicillin from the Sample solution |
| rS | = | = peak response of amoxicillin from the Standard solution |
| CS | = | = concentration of USP Amoxicillin RS in the Standard solution (mg/mL) |
| CU | = | = 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 = (rU/rS) × (CS/CU) × P × 100
| rU | = | = peak response of clavulanic acid from the Sample solution |
| rS | = | = peak response of clavulanic acid from the Standard solution |
| CS | = | = concentration of USP Clavulanate Lithium RS in the Standard solution (mg/mL) |
| CU | = | = 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%
PERFORMANCE TESTS
• Disintegration 
701
:
Tablets labeled for veterinary use only; 30 min, simulated gastric fluid TS being substituted for water in the test
701:
Tablets labeled for veterinary use only; 30 min, simulated gastric fluid TS being substituted for water in the test
• Dissolution 711
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 C8H9NO5 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
905:
Meet the requirements
SPECIFIC TESTS
• Water Determination, Method I 921:
921:
| Tablet Label Claim Amoxicillin (mg/Tablet) |
Acceptance Criteria, NMT (%) |
|---|---|
 250 |
7.5 |
| >250 and 500 |
10.0 |
| >500 | 11.0 |
For products labeled as chewable Tablets:
| Tablet Label Claim Amoxicillin (mg/Tablet) |
Acceptance Criteria, NMT (%) |
|---|---|
| 125 |
6.0 |
| >125 | 8.0 |
For Tablets labeled for veterinary use only:
NMT 10.0%
• Microbial Enumeration Tests 61 and Tests 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.
61 and Tests 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.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers.
• Labeling:
Label chewable Tablets to include the word “chewable” in juxtaposition to the official 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.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Ahalya Wise, M.S.
Senior Scientific Liaison 1-301-816-8161 |
(SM12010) Monographs - Small Molecules 1 |
| 701 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| 61 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| 62 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 2199
Pharmacopeial Forum: Volume No. 36(4) Page 901