Potassium Citrate Extended-Release 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

Potassium Citrate Extended-Release Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of potassium citrate as monohydrate (C₆H₅K₃O₇ · H₂O).

2 IDENTIFICATION

A. Identification Tests - General 〈191〉, Chemical Identification Tests, Potassium

Sample solution: Powder 5 Tablets, mix with 20 mL of water, and filter.

Acceptance criteria: The filtrate meets the requirements.

B. Identification Tests - General 〈191〉, Chemical Identification Tests, Citrate

Sample: A portion of powdered Tablets containing about 50 mg of potassium citrate

Acceptance criteria: Meet the requirements

3 ASSAY

Procedure

Buffer: 3.4 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 2.2.

Mobile phase: Buffer

Standard solution: 0.4 mg/mL of USP Citric Acid RS in Mobile phase

Sample stock solution: Weigh and finely powder NLT 20 Tablets. Transfer a portion of the powder, equivalent to 2000 mg of potassium citrate monohydrate, to a 250-mL volumetric flask, and add 150 mL of hot water (60°–70°). Sonicate for 20 min with occasional shaking. Allow to cool to room temperature, dilute with water to volume, and mix.

Sample solution: Pass a portion of the Sample stock solution through a suitable filter of 0.45-μm pore size, discarding the first 5 mL of filtrate.

Transfer 4 mL of the filtrate to a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix. [Note - Reserve the remaining filtrate for use in the Content of Potassium test.]

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

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

Column temperature: 55°

Flow rate: 1 mL/min

Injection volume: 20 μL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O) in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100

r_U = citric acid peak area from the Sample solution

r_S = citric acid peak area from the Standard solution

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

C_U = nominal concentration of potassium citrate monohydrate in the Sample solution (mg/mL)

M_r1 = molecular weight of potassium citrate monohydrate, 324.41

M_r2 = molecular weight of citric acid (C₆H₈O₇), 192.13

Acceptance criteria: 90.0%–110.0%

4 OTHER COMPONENTS

Content of Potassium

Standard stock solution: 19.07 μg/mL of potassium chloride, previously dried at 105° for 2 h, in water. This solution contains 10 μg/mL of potassium.

Standard solutions: Transfer 10.0, 15.0, and 20.0 mL, respectively, to separate 100-mL volumetric flasks of the Standard stock solution. To each flask, add 2.0 mL of sodium chloride solution (200 mg/mL) and 1.0 mL of hydrochloric acid, and dilute with water to volume. The Standard solutions contain 1.0, 1.5, and 2.0 μg/mL of potassium, respectively.

Sample stock solution: Dilute the clear filtrate, reserved from the Assay, with water to obtain a solution containing about 160 μg/mL of potassium citrate monohydrate.

Sample solution: Transfer 3.0 mL of the Sample stock solution to a 100-mL volumetric flask.

Instrumental conditions

(See Atomic Absorption Spectroscopy 〈852〉.)

Mode: Atomic absorption spectrophotometry

Analytical wavelength: Potassium emission line at 766.5 nm

Lamp: Potassium hollow-cathode

Flame: Air–acetylene

Blank: Water

Analysis

Samples: Standard solutions, Sample solution, and Blank

Plot the absorbance of the Standard solutions versus the concentration of potassium, in μg/mL, and draw the straight line best fitting the three plotted points. From the graph obtained, determine the concentration of potassium in the Sample solution (μg/mL).

Calculate the percentage of potassium (K) in the portion of Tablets taken:

Result = C × 100/C_U

C = concentration of potassium in the Sample solution as determined in this test (μg/mL)

C_U = concentration of potassium citrate anhydrous (C₆H₅K₃O₇) in the Sample solution calculated from the Assay value of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O) (μg/mL)

Acceptance criteria: 36.4%–40.2%

5 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

5.1 Test 1

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Times: 0.5, 1, and 3 h; without Medium replacement

[Note - Withdraw the same volume at each time point.]

Standard stock solution and Standard solutions: Prepare as directed in the Content of Potassium test.

Sample solution: Filter the solution under test and dilute quantitatively with Medium to obtain a solution containing about 60 μg of potassium citrate per mL. Transfer 5.0 mL of this solution to a 100-mL volumetric flask, add 2.0 mL of sodium chloride solution (1 in 5) and 1.0 mL of hydrochloric acid. Dilute with water to volume, and mix.

Instrumental conditions

(See Atomic Absorption Spectroscopy 〈852〉.)

Mode: Atomic absorption spectrophotometry

Analytical wavelength: Potassium emission line at 766.5 nm

Lamp: Potassium hollow-cathode

Flame: Air–acetylene

Blank: Water

Analysis

Samples: Standard solutions, Sample solution, and Blank

Determine the concentration, in μg/mL, of potassium in the Sample solution at each time point.

Calculate the percentage of the labeled amount of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O) dissolved at each time point:

At 0.5 h:

Result₁ = C₁ × V × R × F × 100/L

At 1 h:

Result₂ = [C₂ × (V − V_S) + C₁ × V_S] × R × F × 100/L

At 3 h:

Result₃ = {C₃ × [V − 2 × V_S] + (C₂ + C₁) × V_S} × R × F × 100/L

C = as C₁, C₂, C₃, concentration of potassium in the Sample solution at each time point (μg/mL)

V = volume of Medium, 900 mL

R = ratio of the molecular weight of potassium citrate monohydrate to 3 times the atomic weight of potassium, 2.765

F = dilution factor of the Sample solution

L = label claim (mg/Tablet)

V_S = volume of sample withdrawn at each time point (mL)

Tolerances: The percentages of the labeled amount of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O) dissolved from the Tablets are NMT 45% (Q) in 30 min, NMT 60% (Q′) in 1 h, and NLT 80% (Q′′) in 3 h. The requirements are met if the quantities dissolved from the Tablets tested conform to Table 1 instead of the table shown under Dissolution 〈711〉.

Table 1

Apparatus 2: 50 rpm

Times: 0.5, 1, 4, and 6 h. Replace the volume withdrawn with the equal volume of Medium preheated to 37 ± 0.5°.

Buffer: 3.4 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 2.2.

Mobile phase: Buffer

Standard solution: Prepare a solution of USP Citric Acid RS in Medium as directed in Table 2.

Table 2

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size, discarding the first 5 mL of filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

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

Column temperature: 55°

Flow rate: 1.0 mL/min

Injection volume: 20 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Determine the concentration, in mg/mL, of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O) in the sample withdrawn from the vessel at each time point:

Result = (r_U/r_S) × C_S × (M_r1/M_r2)

r_U = citric acid peak area from the Sample solution

r_S = citric acid peak area from the Standard solution

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

M_r1 = molecular weight of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O), 324.41

M_r2 = molecular weight of citric acid (C₆H₈O₇), 192.13

Calculate the percentage of the labeled amount of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O) dissolved at each time point:

At 0.5 h:

Result₁ = C₁ × V × 100/L

At 1 h:

Result₂ = (C₂ × V + C₁ × V_S) × 100/L

At 4 h:

Result₃ = [C₃ × V + (C₂ + C₁) × V_S] × 100/L

At 6 h:

Result₄ = [C₄ × V + (C₃ + C₂ + C₁) × V_S] × 100/L

C = as C₁, C₂, C₃, C₄, concentration of potassium citrate monohydrate in the portion of sample withdrawn at the specified time point (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

V_S = volume of sample withdrawn at each time point (mL)

Tolerances: The percentages of the labeled amount of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O) dissolved at the times speci fied in Table 3 conform to Dissolution 〈711〉, Acceptance Table 2.

Table 3

5.2 Test 3

If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.

Medium: Water; 900 mL

Apparatus 2: 50 rpm

[Note - Employ sinker if necessary to ensure that the Tablets do not float.]

Times: 0.5, 1, and 5 h; without Medium replacement

[Note - Withdraw the same volume at each time point. Pass a portion of the solution through a 0.45-μm membrane filter, discarding the first 2 mL of the filtrate.]

Diluent: Transfer 5 g of sodium chloride to a 100-mL volumetric flask, add 25 mL of water and 25 mL of concentrated hydrochloric acid, shake until dissolved, cool to room temperature, and dilute with water to volume.

Standard stock solution: 19.07 μg/mL of potassium chloride, previously dried at 105° for 2 h, in water. This solution contains 10 μg/mL of potassium.

Standard solutions: Transfer 5.0, 7.0, 10.0, 15.0, and 20.0 mL of Standard stock solution to separate 100-mL volumetric flasks. Add 4.0 mL of Diluent to each flask, dilute with water to volume, and mix well. The Standard solutions contain 0.5, 0.7, 1.0, 1.5, and 2.0 μg/mL of potassium, respectively.

Sample stock solution: Filter the solution under test, and dilute quantitatively with water as stated in Table 4.

Table 4

Sample solution: Transfer 5.0 mL of respective Sample stock solution into 100-mL volumetric flasks. Add 4.0 mL of Diluent, dilute with water to volume, and mix well.

Instrumental conditions

(See Atomic Absorption Spectroscopy 〈852〉.)

Mode: Atomic absorption spectrophotometry

Analytical wavelength: Potassium emission line at 766.5 nm

Lamp: Potassium hollow-cathode

Flame: Air–acetylene

Blank: Dilute Diluent with water (4:96)

Analysis

Samples: Standard solutions, Sample solution, and Blank

Determine the concentration, in μg/mL, of potassium in the Sample solution at each time point.

Calculate the percentage of the labeled amount of potassium dissolved at each time point:

At 0.5 h:

Result₁ = C₁ × D₁ × V × 100/(L × A)

At 1 h:

Result₂ = [C₂ × D₂ × (V − V_S) + C₁ × D₁ × V_S] × 100/(L × A)

At 5 h:

Result₃ = {C₃ × D₃ × [V − 2 × V_S] + (C₂ × D₂ + C₁ × D₁) × V_S} × D × 100/(L × A)

C = as C₁, C₂, C₃, concentration of potassium in the Sample solution at each time point (mg/mL)

D = as D₁, D₂, D₃, dilution factor of the Sample solution at each point

V = volume of Medium, 900 mL

L = label claim (mEq/Tablet)

A = atomic weight of potassium, 39.1

V_S = volume of sample withdrawn at each time point (mL)

Tolerances: The percentages of the labeled amount of potassium dissolved at the times specified in Table 5 conform to Dissolution 〈711〉, Acceptance Table 2.

Table 5

5.3 Test 4

If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4.

Medium: Water; 900 mL

Apparatus 2: 50 rpm

[Note - Use tablet sinkers if necessary.]

Times: 0.5, 1, and 6 h. Replace the volume withdrawn with the equal volume of Medium preheated to 37 ± 0.5°.

[Note - Withdraw the same volume at each time point. Pass a portion of the withdrawn solution through a 0.45-μm nylon filter, discarding the first 5 mL of filtrate.]

Buffer and Mobile phase: Prepare as directed in Test 2.

Standard solution: Prepare a solution of USP Citric Acid RS in Medium as directed in Table 6.

Table 6

Sample solution: Filtered portion of the solution under test

Chromatographic system and System suitability: Proceed as directed in Test 2.

Analysis

Samples: Standard solution and Sample solution

Determine the concentration, in mg/mL, of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O) in the sample withdrawn from the vessel at

each time point:

Result = (r_U/r_S) × C_S × (M_r1/M_r2)

r_U = peak area of citric acid from the Sample solution

r_S = peak area of citric acid from the Standard solution

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

M_r1 = molecular weight of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O), 324.41

M_r2 = molecular weight of citric acid (C₆H₈O), 192.13

Calculate the percentage of the labeled amount of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O) dissolved at each time point:

At 0.5 h:

Result₁ = C₁ × V × (100/L)

At 1 h:

Result₂ = (C₂ × V + C₁ × V_S) × (100/L)

At 6 h:

Result₃ = [C₃ × V + (C₂ + C₁) × V_S] × 100/L

C_i = concentration of potassium citrate monohydrate in the portion of sample withdrawn at the specified time point (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

V_S = volume of sample withdrawn at each time point (mL)

Tolerances: The percentages of the labeled amount of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O) dissolved at the times specified in Table 7 conform to Dissolution 〈711〉, Acceptance Table 2.

Table 7

5.4 Test 5

 If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 5.

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Times: 0.5, 1, 2 and 6 h. Replace the volume withdrawn with an equal volume of Medium preheated to 37 ± 0.5°.

[Note - Withdraw the same volume at each time point. Pass a portion of the withdrawn solution through a 0.45-μm nylon filter, discarding the first 5 mL of filtrate.]

Buffer and Mobile phase: Prepare as directed in Test 2.

Standard solution: Prepare a solution of USP Citric Acid RS in Medium as directed in Table 8.

Table 8

Sample solution: Filtered portion of the solution under test

Chromatographic system and System suitability: Proceed as directed in Test 2.

Analysis

Samples: Standard solution and Sample solution

Determine the concentration, in mg/mL, of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O) in the sample withdrawn from the vessel at each time point:

Result = (r_U/r_S) × C_S × (M_r1/M_r2)

r_U = peak area of citric acid from the Sample solution

r_S = peak area of citric acid from the Standard solution

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

M_r1 = molecular weight of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O), 324.41

M_r2 = molecular weight of citric acid (C₆H₈O), 192.13

Calculate the percentage of the labeled amount of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O) dissolved at each time point:

At 0.5 h:

Result₁ = C₁ × V × 100/L

At 1 h:

Result₂ = (C₂ × V + C₁ × V_S) × 100/L

At 2 h:

Result₃ = [C₃ × V + (C₂ + C₁) × V_S] × 100/L

At 6 h:

Result₄ = [C₄ × V + (C₃ + C₂ + C₁) × V_S] × 100/L

C_i = concentration of potassium citrate monohydrate in the portion of sample withdrawn at the speci

ed time point (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

V_S = volume of sample withdrawn at each time point (mL)

Tolerances:

See Table 9.

Table 9

The percentages of the labeled amount of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.

5.5 Test 6

If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 6.

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Times: 0.5, 1, and 4 h - for strength 540 mg as potassium citrate monohydrate; 0.5, 1, and 6 h - for strengths 1080 and 1620 mg as potassium citrate monohydrate. Replace the volume withdrawn with an equal volume of Medium preheated to 37 ± 0.5°.

[Note - Withdraw the same volume at each time point. Pass a portion of the withdrawn solution through a suitable 0.45-μm filter, discarding the first 5 mL of filtrate.]

Buffer, Mobile phase, Standard solution, Chromatographic system, and System suitability: Proceed as directed in Test 2.

Sample solution: Filtered portion of the solution under test

Analysis

Samples: Standard solution and Sample solution

Determine the concentration, in mg/mL, of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O) in the sample withdrawn from the vessel at each time point:

Result = (r_U/r_S) × C_S × (M_r1/M_r2)

r_U = peak area of citric acid from the Sample solution

r_S = peak area of citric acid from the Standard solution

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

M_r1 = molecular weight of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O), 324.41

M_r2 = molecular weight of citric acid (C₆H₈O), 192.13

Calculate the percentage of the labeled amount of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O) dissolved at each time point:

At 0.5 h:

Result₁ = C₁ × V × 100/L

At 1 h:

Result₂ = (C₂ × V + C₁ × V_S) × 100/L

At 4 h or 6 h:

Result₃ = [C₃ × V + (C₂ + C₁) × V_S] × 100/L

C = concentration of potassium citrate monohydrate in the portion of sample withdrawn at the specified time point (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

V_S = volume of sample withdrawn at each time point (mL)

Tolerances: See Table 10 and Table 11.

Table 10. For Tablets Labeled to Contain 540 mg/Tablet

Table 11. For Tablets Labeled to Contain 1080 and 1620 mg/Tablet

The percentages of the labeled amount of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.

5.6 Test 7

If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 7.

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Times: 0.5, 1, 2 and 6 h. Replace the volume withdrawn with an equal volume of Medium preheated to 37 ± 0.5°.

[Note - Withdraw the same volume at each time point. Pass a portion of the withdrawn solution through a nylon filter of 0.45-μm pore size, discarding the first 5 mL of filtrate.]

Buffer, Mobile phase, and Standard solution: Prepare as directed in Test 2.

Sample solution: Filtered portion of the solution under test

Chromatographic system and System suitability: Proceed as directed in Test 2.

Analysis

Samples: Standard solution and Sample solution

Determine the concentration, in mg/mL, of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O) in the sample withdrawn from the vessel at each time point:

Result = (r_U/r_S) × C_S × (M_r1/M_r2)

r_U = peak area of citric acid from the Sample solution

r_S = peak area of citric acid from the Standard solution

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

M_r1 = molecular weight of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O), 324.41

M_r2 = molecular weight of citric acid (C₆H₈O), 192.13

Calculate the percentage of the labeled amount of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O) dissolved at each time point:

At 0.5 h:

Result₁ = C₁ × V × 100/L

At 1 h:

Result₂ = (C₂ × V + C₁ × V_S) × 100/L

At 2 h:

Result₃ = [C₃ × V + (C₂ + C₁) × V_S] × 100/L

At 6 h:

Result₄ = [C₄ × V + (C₃ + C₂ + C₁) × V_S] × 100/L

C_i = concentration of potassium citrate monohydrate in the portion of sample withdrawn at the specified time point (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

V_S = volume of sample withdrawn at each time point (mL)

Tolerances:

See Table 12.

Table 12

The percentages of the labeled amount of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O) dissolved at the times specified conform toDissolution 〈711〉, Acceptance Table 2. (RB 1-Aug-2024)

Uniformity of Dosage Units 〈905〉: Meet the requirements.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

Labeling: The label states the amount of potassium citrate as monohydrate (C₆H₅K₃O₇ · H₂O) in mEq and in g/Tablet. The label indicates the

Dissolution test with which the product complies.

USP Reference Standards 〈11〉

USP Citric Acid RS