Potassium Chloride Extended-Release 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

Potassium Chloride Extended-Release Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of potassium chloride (KCl).

2 IDENTIFICATION

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

Sample solution: A portion of the filtrate, obtained as directed for Sample stock solution in the Assay

Acceptance criteria: Meet the requirements

B. Identification Tests—General 〈191〉, Chemical Identification Tests, Chloride

Sample solution: A portion of the filtrate, obtained as directed for Sample stock solution in the Assay

Acceptance criteria: Meet the requirements

3 ASSAY

Procedure

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: To separate 100-mL volumetric flasks transfer 10.0, 15.0, and 20.0 mL, respectively, of 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, respectively, 1.0, 1.5, and 2.0 µg/mL of potassium.

Sample stock solution: Place NLT 20 Capsules in a suitable container with 400 mL of water, heat to boiling, and boil for 20 min. Allow to cool, transfer the solution to a 1000-mL volumetric flask, and dilute with water to volume. Filter, discarding the first 20 mL of the filtrate. Transfer a measured volume of the subsequent filtrate, equivalent to 60 mg of potassium chloride, to a 1000-mL volumetric flask, and dilute with water to volume. [Note—Retain a portion of the filtrate for use in the Identification tests.]

Sample solution: Transfer 5.0 mL of Sample stock solution to a 100-mL volumetric 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.

3.1 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

3.2 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, determine the concentration of potassium in the Sample solution (µg/mL).

Calculate the percentage of the labeled amount of potassium chloride (KCl) in each Capsule taken:

Result = (C/C_U ) × (M_r /A_r ) × 100

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

C = concentration of potassium chloride in the Sample solution (µg/mL)

M_r = molecular weight of potassium chloride, 74.55

A_r = atomic weight of potassium, 39.10

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

4.1 Test 1

Medium: Water; 900 mL

Apparatus 1: 100 rpm

Time: 2 h

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: To separate 100-mL volumetric flasks transfer 10.0, 15.0, and 20.0 mL, respectively, of 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, respectively, 1.0, 1.5, and 2.0 µg/mL of potassium.

Sample stock solution: Filter the solution under test, and dilute quantitatively with Medium to obtain a solution containing 60 µg/mL of potassium chloride.

Sample solution: Add 5.0 mL of the Sample stock solution to a 100-mL volumetric 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.

4.1.1 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

4.1.2 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 tting the three plotted points. From the graph, determine the concentration of potassium in the Sample solution (µg/mL). Calculate the percentage of the labeled amount of potassium chloride (KCl) dissolved:

Result = [C × D × (V/L)] × (M_r /A_r ) × 100

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

D = dilution factor of the Sample solution

V = volume of Medium, 900 mL

L = labeled amount of potassium chloride (µg/Capsule)

M_r = molecular weight of potassium chloride, 74.55

A_r = atomic weight of potassium, 39.10

Tolerances: NMT 35% (Q) of the labeled amount of potassium chloride (KCl) is dissolved in 2 h. The requirements are met if the quantities dissolved from the Capsules tested conform to Table 1 instead of to the table shown in Dissolution 〈711〉.

Table 1

4.2 Test 2

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

Standard stock solution and Standard solutions: Prepare as directed in Test 1.

Medium: Water; 900 mL

Apparatus 1: 100 rpm

Times: 1, 2, 4, and 6 h

Sample stock solution: Transfer 4.0 mL of the solution under test into a 50-mL volumetric flask, dilute with water to volume, and filter. Sample solution: Transfer 4.0 mL of the Sample stock solution to a 100-mL volumetric 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.

Blank solution: To a 100-mL volumetric 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.

Instrumental conditions: Proceed as directed in Test 1, except do not use the Blank.

4.2.1 System suitability

Samples: Standard solutions

Suitability requirements

Linearity: Correlation coefficient NLT 0.99

Relative standard deviation: NMT 5.0% from 5 replicate analyses of the 1.5-µg/mL Standard solution

4.2.2 Analysis

Samples: 1.5-µg/mL Standard solution, Sample solution, and Blank solution

Calculate the percentage of the labeled amount of potassium chloride (KCl) dissolved:

Result_i = [(A_U /A_S ) × C_S × D × (V/L)] × (M_r /A_r ) × 100

A_U = absorbance of potassium in the Sample solution

A_S = absorbance of potassium in the Standard solution

C_S = concentration of potassium in the Standard solution (µg/mL)

D = dilution factor of the Sample solution

V = volume of Medium, 900 mL

L = labeled amount of potassium chloride (µg/Capsule)

M_r = molecular weight of potassium chloride, 74.55

A_r = atomic weight of potassium, 39.10

Tolerances: See Table 2.

Table 2

The percentages of the labeled amount of potassium chloride (KCl), dissolved at the times specied, conform to Dissolution 〈711〉, Acceptance Table 2.

4.3 Test 3

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

[Note—Use water with a conductivity of NMT 1 μS/cm to prepare solutions, except Medium.]

Medium: Water; 900 mL

Apparatus 1: 100 rpm

Times: 1, 2, 4, and 8 h

Solution A: 100 mM methanesulfonic acid prepared as follows. Transfer 6.5 mL of methanesulfonic acid to a 1000-mL volumetric flask and dilute with water to volume.

Mobile phase: Solution A and water (20:80)

Standard stock solution: 600 μg/mL of USP Potassium Chloride RS in water

Standard solution A: 3 μg/mL of USP Potassium Chloride RS in water from Standard stock solution

Standard solution B: 12 μg/mL of USP Potassium Chloride RS in water from Standard stock solution

Standard solution C: 30 μg/mL of USP Potassium Chloride RS in water from Standard stock solution

Standard solution D: 48 μg/mL of USP Potassium Chloride RS in water from Standard stock solution

Standard solution E: 60 μg/mL of USP Potassium Chloride RS in water from Standard stock solution

Standard solution F: 72 μg/mL of USP Potassium Chloride RS in water from Standard stock solution

Standard solution G: 90 μg/mL of USP Potassium Chloride RS in water from Standard stock solution

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size at the times specified, discarding the first few milliliters of the filtrate. Replace the portion removed with same volume of Medium. Dilute the filtrate with water, if necessary, to obtain a solution with a concentration similar to that of Standard solution E.

4.3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: Conductivity with suppression

Columns

Guard: 4-mm × 5-cm; 8.5-µm packing L106

Analytical: 4-mm × 25-cm; 8.5-µm packing L106

Suppressor: 4-mm cation or a suitable suppressor

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 50 μL

Run time: NLT 2.5 times the retention time of potassium

4.3.2 System suitability

Samples: Standard solution A, Standard solution B, Standard solution C, Standard solution D, Standard solution E, Standard solution F, and Standard solution G

Suitability requirements

Tailing factor: NMT 2.0, Standard solution E

Relative standard deviation: NMT 2.0%, Standard solution E

Correlation coefficient: NLT 0.999, from the linear regression in the Analysis

Y-intercept: ±2% of Standard solution E response, from the calibration curve in the Analysis

4.3.3 Analysis

Samples: Standard solution A, Standard solution B, Standard solution C, Standard solution D, Standard solution E, Standard solution F, Standard solution G, and Sample solution

Determine the responses for Standard solution A, Standard solution B, Standard solution C, Standard solution D, Standard solution E, Standard solution F, and Standard solution G. Construct a linear calibration curve by plotting response values of Standard solution A,

Standard solution B, Standard solution C, Standard solution D, Standard solution E, Standard solution F, and Standard solution G versus their corresponding concentrations in mg/mL.

From the linear calibration curve, determine the Correlation coefficient and Y-intercept.

Calculate the concentration (C ) of potassium chloride (KCl) in the sample withdrawn from the vessel at time point i: i

Result = (r_U /r_S ) × C_S × D

r_U = peak response of potassium from the Sample solution at time point i

r_S = peak response of potassium from Standard solution E

C_S = concentration of USP Potassium Chloride RS in Standard solution E (mg/mL)

D = dilution factor of the Sample solution, if needed

Calculate the percentage of the labeled amount of potassium chloride (KCl) dissolved at each time point (i):

Result₁ = C₁ × V × (1/L) × 100

Result₂ = [(C₂ × V) + (C₁ × V_S )] × (1/L) × 100

Result₃ = {(C₃ × V) + [(C₂ + C₁ ) × V_S ]} × (1/L) × 100

Result₄ = {(C₄ × V) + [(C₃ + C₂ + C₁ ) × V_S ]} × (1/L) × 100

C_i = concentration of potassium chloride in the portion of sample withdrawn at time point i (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/capsule)

V_S = volume of the Sample solution withdrawn at each time point (mL)

Tolerences: See Table 3.

Table 3

The percentage of the labeled amount of potassium chloride (KCl) dissolved at the times specied conforms to Dissolution 〈711〉, Acceptance Table 2. (RB 1-Jan-2021)

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at a temperature not exceeding 30°.

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

USP Reference Standards 〈11〉

USP Potassium Chloride RS (RB 1-Jan-2021)