Ferrous Gluconate Capsules

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

1 DEFINITION

Ferrous Gluconate Capsules contain NLT 93.0% and NMT 107.0% of the labeled amount of ferrous gluconate dihydrate (C₁₂H₂₂FeO₁₄ · 2H₂O). 

2 IDENTIFICATION

2.1 A. Thin-Layer Chromatography

Standard solution: 10 mg/mL of USP Potassium Gluconate RS

Sample solution: A filtered solution in water, equivalent to 10 mg/mL of ferrous gluconate dihydrate from the contents of the Capsules

2.1.1 Chromatographic system

(See Chromatography 〈621〉, Thin-Layer Chromatography.)

Mode: TLC

Adsorbent: 0.25-mm layer of chromatographic silica gel

Application volume: 5 µL

Developing solvent system: Alcohol, ethyl acetate, ammonium hydroxide, and water (50:10:10:30)

Spray reagent: Dissolve 2.5 g of ammonium molybdate in 50 mL of 2 N sulfuric acid in a 100-mL volumetric ask. Add 1.0 g of ceric sulfate, swirl to dissolve, and dilute with 2 N sulfuric acid to volume.

2.1.2 Analysis

Samples: Standard solution and Sample solution

Develop the chromatogram until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the chamber, and dry at 110° for 20 min. Allow to cool, and spray with Spray reagent. Heat the plate at 110° for about 10 min. Acceptance criteria: The principal spot of the Sample solution corresponds in color, size, and R value to that of the Standard solution. F

2.2 B. Ferrous Ion

Sample solution: Equivalent to 5 mg/mL of ferrous gluconate dihydrate from a dilution of the Sample solution obtained in Identification test A Analysis: Add potassium ferricyanide TS to the Sample solution.

Acceptance criteria: The solution yields a dark blue precipitate.

3 ASSAY

Procedure

Buffer: Dissolve 3.0 g of sodium acetate in 50 mL of water. Add 2.0 mL of glacial acetic acid, dilute with water to 200 mL, and mix. This Buffer has a pH of 4.6.

Color reagent solution: Dissolve 400 mg of 2,2′-bipyridine in 100 mL of water, using heat if necessary, to dissolve. Cool, and filter. Standard stock solution: 7.022 mg/mL of ferrous ammonium sulfate hexahydrate [Fe(NH ) (SO )  · 6H O] in water, equivalent to 1000 µg/mL

of iron (Fe)

Standard solution: 100 µg/mL of iron (Fe) in 0.1 N sulfuric acid from Standard stock solution

Sample solution

For hard gelatin capsules: Transfer, as completely as possible, the contents of NLT 20 Capsules to a suitable tared container. Mix and nely powder the combined contents, and transfer a weighed portion of the powder, equivalent to 430 mg of ferrous gluconate dihydrate, to a 500-mL volumetric ask. Add 300 mL of water, heating on a steam bath if necessary to dissolve. Cool, and dilute with water to volume.

For soft gelatin capsules: Place a number of Capsules, equivalent to 430 mg of ferrous gluconate dihydrate, in a 500-mL volumetric ask. Add 300 mL of water, heating on a steam bath to dissolve the Capsules. Cool, and dilute with water to volume.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV-Vis

Analytical wavelength: 522 nm

Cell: 1 cm

Analysis

Samples: Standard solution and Sample solution

Transfer 3.0 mL of the Sample solution to a 100-mL volumetric ask, and add, in the order named, 70 mL of Buffer, 10.0 mL of 100 mg/mL of sodium thiosulfate solution, and 5.0 mL of Color reagent solution, with mixing following each addition. Heat for 60 min on a steam bath, cool, dilute with Buffer to volume, and filter. Prepare reagent blanks for the Standard solution and the Sample solution by repeating the above procedure, omitting the addition of 5.0 mL of Color reagent solution.

Concomitantly determine the absorbances of the reacted solutions against the corresponding reagent blanks.

Calculate the percentage of the labeled amount of ferrous gluconate dihydrate (C₁₂H₂₂FeO₁₄ · 2H₂O) in the portion of Capsules taken:

Result = (A_U /A_S ) × (C_S /C_U ) × (M_r /A_r ) × 100

A_U = absorbance of the Sample solution corrected by the absorbance of its reagent blank

A_S = absorbance of the Standard solution corrected by the absorbance of its reagent blank

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

C_U = nominal concentration of ferrous gluconate dihydrate in the Sample solution (µg/mL)

M_r = molecular weight of ferrous gluconate dihydrate, 482.17

A_r = atomic weight of iron, 55.85

Acceptance criteria: 93.0%–107.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 1: 100 rpm

Time: 45 min

Standard solution: Solution having a known concentration of iron in the Medium

Sample solution: Filtered portion of the solution under test, suitably diluted with the Medium if necessary Instrumental conditions

(See Atomic Absorption Spectroscopy 〈852〉.)

Mode: Atomic absorption spectrophotometry

Analytical wavelength: 248.3 nm

Lamp: Iron hollow-cathode

Flame: Air–acetylene

Analysis

Samples: Standard solution and Sample solution

Determine the concentration of iron (Fe) in the Sample solution in comparison with a Standard solution. Calculate the percentage of the labeled amount of ferrous gluconate dihydrate (C₁₂H₂₂FeO₁₄ · 2H₂O) dissolved:

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

M_r = molecular weight of ferrous gluconate dihydrate, 482.17

A_r = atomic weight of iron, 55.85

C = measured concentration of iron in the Sample solution (mg/mL)

D = dilution factor for the Sample solution

V = volume of Medium, 900 mL

L = label amount of ferrous gluconate dihydrate (mg/Capsule)

Tolerances: NLT 75% (Q) of the labeled amount of ferrous gluconate dihydrate (C₁₂H₂₂FeO₁₄ · 2H₂O) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

Labeling: Label the Capsules in terms of the content of ferrous gluconate dihydrate (C₁₂H₂₂FeO₁₄ · 2H₂O) and in terms of the content of elemental iron.

USP Reference Standards 〈11〉

USP Potassium Gluconate RS.