Divalproex Sodium Delayed-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

Divalproex Sodium Delayed-Release Tablets contain an amount of Divalproex Sodium equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of valproic acid (C₈H₁₆O₂).

2 IDENTIFICATION

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

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

3 ASSAY

Procedure

Solution A: 0.50 g/L of citric acid and 0.40 g/L of dibasic sodium phosphate in water

Mobile phase: Acetonitrile and Solution A (30:70). Adjust with phosphoric acid to a pH of 3.0 ± 0.1.

Standard solution: 0.5 mg/mL of USP Valproic Acid RS in Mobile phase

Sample stock solution: Nominally 10 mg/mL of valproic acid, prepared as follows. Transfer a number of whole Tablets to an appropriate volumetric flask. Add 60% of the flask volume of Mobile phase, and sonicate with frequent swirling for 30 min or until the Tablets completely disintegrate. Allow the solution to cool down to room temperature, and then dilute with Mobile phase to volume.

Sample solution: Nominally 0.5 mg/mL of valproic acid from Sample stock solution in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm. For Identi

cation B, use a diode array detector in the range of 190–400 nm.

Column: 3.9-mm × 15-cm; 4-μm packing L11

Flow rate: 0.9 mL/min

Injection volume: 15 μL

Run time: NLT 1.8 times the retention time of valproic acid

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 valproic acid (C₈H₁₆O₂) in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U= peak area of valproic acid from the Sample solution

r_S= peak area of valproic acid from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Acid stage

Acid stage medium: 0.08 N hydrochloric acid (prepared by adding 40 mL of hydrochloric acid to 5000 mL of water, adjusting with 2 N hydrochloric acid to a pH of 1.2, and diluting with water to 6000 mL); 900 mL

Apparatus 2: 50 rpm

Time: 1 h

At the end of 1 h, carefully transfer the Tablet to a dissolution vessel containing the Buffer stage medium. [Note—Do not perform an analysis of the Acid stage medium.]

Buffer stage

Buffer stage medium: pH 7.5 phosphate buffer (6.8 g/L of monobasic potassium phosphate and 1.6 g/L of sodium hydroxide in water,

prepared as follows. Transfer suitable quantities of monobasic potassium phosphate and sodium hydroxide to an appropriate container.

Dilute with water to 80% of the final volume, adjust with 0.08 N hydrochloric acid to a pH of 7.5, and dilute with water to the final volume); 900 mL

Apparatus 2: 50 rpm

Time: 1 h

Solution A: 0.5 g/L of citric acid and 0.4 g/L of dibasic sodium phosphate in water

Solution B: 6.8 g/L of monobasic potassium phosphate and 1.7 g/L of sodium hydroxide in water. Adjust with phosphoric acid to a pH of 7.4 ± 0.1.

Mobile phase: Acetonitrile, Solution A, and Solution B (30:35:35). Adjust with phosphoric acid to a pH of 3.0 ± 0.1.

Standard solution: 0.12 mg/mL of USP Valproic Acid RS in Buffer stage medium. [Note—NMT 10.0% of the flask volume of acetonitrile may be used to dissolve the USP Valproic Acid RS.]

Sample solution: Nominally 0.12 mg/mL of valproic acid, prepared as follows. Pass a portion of the solution under test through a suitable filter. Dilute with Buffer stage medium, if necessary.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 3.9-mm × 15-cm; 4-μm packing L11

Flow rate: 1.2 mL/min

Injection volume: 50 μL

Run time: NLT 1.5 times the retention time of valproic acid

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 valproic acid (C₈H₁₆O₂) dissolved:

Result = (r_U/r_S) × C_S × V × D × (1/L) × 100

r_U= peak area of valproic acid from the Sample solution

r_S= peak area of valproic acid from the Standard solution

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

V = volume of Buffer stage medium, 900 mL

D = dilution factor of the Sample solution

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of valproic acid (C₈H₁₆O₂) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Valproic Acid RS