Glyburide 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

Glyburide Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of glyburide (C₂₃H₂₈CIN₃O₅S).

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K

Sample: Grind a number of Tablets, equivalent to 15 mg of glyburide, to a fine powder. Add 30 mL of acetonitrile, and shake. Filter the mixture, evaporate the filtrate to dryness, and dry the residue under vacuum at 60° for 3 h.

Acceptance criteria: Meet the requirements

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 PROCEDURE

Mobile phase: Dissolve 2.6 g of monobasic ammonium phosphate in 450 mL of water. Add 550 mL of acetonitrile, filter, and degas. Adjust, if necessary, with phosphoric acid or sodium hydroxide to a pH of 5.25 ± 0.30.

System suitability stock solution: 0.1 mg/mL of USP Glyburide Related Compound A in acetonitrile

System suitability solution: To 10 mg of USP Glyburide RS add 20 mL of the System suitability stock solution, and shake vigorously to dissolve. Add 4.0 mL of water.

Standard solution: To 10 mg of USP Glyburide RS add 20.0 mL of acetonitrile, and shake vigorously to dissolve. Add 4.0 mL of water.

Sample solution: Transfer NLT 20 Tablets to a suitable container. Add water equivalent to 0.4 mL of water per mg of glyburide, and swirl to disperse and wet Tablet material. Then add acetonitrile equivalent to 2.0 mL of acetonitrile per mg of glyburide, and shake for 30 min. Centrifuge a portion of the suspension, and use the clear supernatant.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm x 25-cm; packing L7

Flow rate: 2 mL/min

Injection volume: 10 µL

3.3 System suitability

Sample: System suitability solution

[NOTE-The relative retention times for glyburide related compound A and glyburide are about 0.5 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 4.0 between glyburide related compound A and glyburide

Relative standard deviation: NMT 2.0% for glyburide

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of glyburide (C₂₃H₂₈CIN₃O₅S) in the portion of Tablets taken:

Result = (r_U/r_S) x (W_S/V_S)/(W_U/V_U) x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

W_S = weight of USP Glyburide RS, used to prepare the Standard solution (mg)

V_S = sum of volumes of acetonitrile and water used to prepare the Standard solution (mL)

W_U = nominal amount of glyburide used to prepare the Sample solution (mg)

V_U = sum of volumes of acetonitrile and water used to prepare the Sample solution (mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

DISSOLUTION (711)

4.1 Test 1 (nonmicronized glyburide)

Medium: 0.05 M borate buffer, pH 9.5 (381.5 g of sodium borate and 19.1 g of sodium hydroxide in 20 L of water, and adjust with phosphoric acid to a pH of 9.5 ± 0.1); 500 mL

Apparatus 2: 75 rpm

Time: 45 min

Mobile phase: Acetonitrile and water (1:1) containing 4.0 mL of phosphoric acid per L of solution

Standard stock solution: 0.15 mg/mL of USP Glyburide RS in Medium. Sonicate for about 25 min to dissolve, and dilute with Medium to volume.

Standard solutions: Dilute the Standard stock solution with Medium to obtain 0.003 mg/mL (for Tablets labeled to contain 1.5 mg), 0.006 mg/mL (for Tablets labeled to contain 3.0 mg), 0.009 mg/mL (for Tablets labeled to contain 4.5 mg), and 0.012 mg/mL (for Tablets labeled to contain 6.0 mg).

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

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm × 30-cm; 10-µm packing L1

Flow rate: 2 mL/min

Injection volume: 50 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 3.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of glyburide (C₂₃H₂₈CIN₃O₅S) dissolved:

Result = (r_U/r_S) x (C_S/L) x V x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 500 mL

Tolerances: NLT 70% (Q) of the labeled amount of glyburide (C₂₃H₂₈CIN₃O₅S) is dissolved.

4.2 Test 2 (micronized glyburide): If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2

Medium: 0.05 M phosphate buffer, pH 8.5 (6.8 g of monobasic potassium phosphate and 1.99 g of sodium hydroxide in 1 L of water, and adjust with diluted phosphoric acid or diluted sodium hydroxide to a pH of 8.5 ± 0.05); 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Mobile phase: Acetonitrile and water containing 5 g/L of monobasic ammonium phosphate (480:520)

Standard stock solution: Transfer 67 mg of USP Glyburide RS to a 500-mL volumetric flask, dissolve in 40 mL of methanol with sonication for 5 min, and dilute with Medium to volume.

Standard solutions: Dilute the Standard stock solution with Medium to obtain solutions having known concentrations of 0.0017 mg/mL (for Tablets labeled to contain 1.5 mg), 0.0034 mg/mL (for Tablets labeled to contain 3 mg), 0.0047 mg/mL (for Tablets labeled to contain 4.5 mg), and 0.0067 mg/mL (for Tablets labeled to contain 6 mg).

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.5-µm pore size.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.0-mm x 25-cm; 10-µm packing L7

Flow rate: 1.5 mL/min

Injection volume: 50 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

Calculate the percentage of the labeled amount of glyburide (C₂₃H₂₈CIN₃O₅S) dissolved:

Result = (r_U/r_S) x (C_S/L) x V x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: NLT 75% (Q) of the labeled amount of glyburide (C₂₃H₂₈CIN₃O₅S) is dissolved.

4.3 Test 3 (micronized glyburide): If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3

Medium: 0.05 M phosphate buffer, pH 7.5 (40.8 g of monobasic potassium phosphate and 9.4 g of sodium hydroxide, in 6 L of water, and adjust with diluted sodium hydroxide to a pH of 7.5 ± 0.1); 900 mL

Apparatus 2: 50 rpm

Time: 45 min

Mobile phase: Proceed as directed in the Assay.

Diluent: Acetonitrile and water (5:1)

Standard stock solution: 0.67 mg/mL of USP Glyburide RS in Diluent

Standard solution: 6.7 µg/mL of USP Glyburide RS in Medium from the Standard stock solution

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

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm x 25-cm; packing L7

Flow rate: 2 mL/min

Injection volume: 75 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 glyburide (C₂₃H₂₈CIN₃O₅S) dissolved:

Result = (r_U/r_S) x (C_S/L) x V x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: NLT 75% (Q) of the labeled amount of glyburide (C₂₃H₂₈CIN₃O₅S) is dissolved.

4.4 Test 4 (nonmicronized glyburide): If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4

Medium: 0.05 M borate buffer, pH 8.0, with 0.014 M hexadecyltrimethylammonium bromide (prepared by dissolving about 180.0 g of hexadecyltrimethylammonium bromide, 55.6 g of boric acid, 67.1 g of potassium chloride, and 2.8 g of sodium hydroxide in 1500 mL of water at 50° under vigorous stirring for several hours, cooling to room temperature, diluting with water to 2000 mL, adjusting with diluted hydrochloric acid or diluted sodium hydroxide to a pH of 8.00 ± 0.05, and diluting 50 mL of this solution with water to 900 mL); 900 mL

Apparatus 1: 50 rpm

Time: 45 min

Mobile phase: Acetonitrile and water (11:9) containing 5.2 g of monobasic ammonium phosphate for each 2 L

Standard stock solution: 0.27 mg/mL of USP Glyburide RS in alcohol. Transfer 1.0 mL of this solution to a 100-mL volumetric flask, and dilute with Medium to volume.

Standard solution: 2.8 µg/mL of USP Glyburide RS in Medium from the Standard stock solution

Sample solution: Pass a portion of the solution under test through a suitable filter of 5-µm pore size.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 226 nm

Column: 4.6-mm x 25-cm; packing L7

Flow rate: 2 mL/min

Injection volume: 100 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

Calculate the percentage of the labeled amount of glyburide (C₂₃H₂₈CIN₃O₅S) dissolved:

Result = (r_U/r_S) x (C_S/L) x V x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: NLT 75% (Q) of the labeled amount of glyburide (C₂₃H₂₈CIN₃O₅S) is dissolved.

4.5 Test 5 (micronized glyburide): If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 5

Medium: 0.05 M phosphate buffer, pH 7.5 (40.8 g of monobasic potassium phosphate and 9.4 g of sodium hydroxide, in 6 L of water, and adjust with diluted sodium hydroxide to a pH of 7.5 ± 0.1); 900 mL

Apparatus 2: 50 rpm

Standard solution: USP Glyburide RS in Medium in a concentration similar to the one expected in the Sample solution

Time: 30 min

Sample solution: Pass a portion of the solution under test through a suitable filter. Dilute with Medium, if necessary.

Mobile phase, Diluent, Chromatographic system, System suitability, and Analysis: Proceed as directed for Test 3.

Tolerances: NLT 75% (Q) of the labeled amount of glyburide (C₂₃H₂₈CIN₃O₅S) is dissolved.

5 IMPURITIES

ORGANIC IMPURITIES

Mobile phase: Dissolve 0.087 g of dibasic potassium phosphate and 0.612 g of monobasic potassium phosphate in 550 mL of water to obtain a solution with a pH of 6.00 ± 0.05. Add 450 mL of methanol.

Diluent: Dissolve 0.871 g of dibasic potassium phosphate in 550 mL of water, and dilute with methanol to 1 L.

Standard stock solution: 0.1 mg/mL each of USP Glyburide RS and USP Glyburide Related Compound A RS in methanol

Standard solution: 0.0004 mg/mL each of USP Glyburide RS and USP Glyburide Related Compound A RS in Mobile phase from the Standard stock solution. This solution is stable for 48 h when stored at room temperature.

Sample solution: Weigh, and powder NLT 20 Tablets. Transfer a portion of the powder, equivalent to about 20 mg of glyburide, to a 100-mL volumetric flask. Add 80 mL of Diluent, and sonicate for 15 min, then shake the flask for 10 min. Dilute with Diluent to volume, and mix. Centrifuge a portion of this solution, and use a clear supernatant. This solution is stable for 14 h when stored at room temperature.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 3.9-mm × 15-cm; 4-µm packing L7

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

[NOTE-The relative retention times for glyburide related compound A and glyburide are about 0.3 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 15 between glyburide related compound A and glyburide

Relative standard deviation: NMT 5% for glyburide related compound A

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of glyburide related compound A in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of glyburide related compound A from the Sample solution

r_S = peak response of glyburide related compound A from the Standard solution

C_S = concentration of USP Glyburide Related Compound A RS in the Standard solution (mg/mL)

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

Acceptance criteria

Glyburide related compound A: NMT 5.3%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in well-closed containers. Store at controlled room temperature.

6.2 LABELING

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

Change to read:

6.3 USP REFERENCE STANDARDS (11)

USP Glyburide RS

USP Glyburide Related Compound A RS

4-[2-(5-Chloro-2-methoxybenzamido)ethyl] benzenesulfonamide. (ERR 1-Oct-2021)

C₁₆H₁₇CIN₂O₄S 368.83