Lactose Monohydrate

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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Portions of the monograph text that are national USP text, and are not part of the harmonized text, are marked with symbols (*) to specify this fact.

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1 DEFINITION

Lactose Monohydrate is the monohydrate of O-B-D-galactopyranosyl-(1-4)-a-D-glucopyranose. (NF 1-Dec-2024) [NOTE-Lactose Monohydrate may be modified as to its physical characteristics. It may contain varying proportions of amorphous lactose.] (NF 1-Dec-2024)

2 IDENTIFICATION

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

B. THIN-LAYER CHROMATOGRAPHIC IDENTIFICATION TEST (201)

Diluent: Methanol and water (3:2)

Standard solution A: 0.5 mg/mL of USP Lactose Monohydrate RS in Diluent

Standard solution B: 0.5 mg/mL each of USP Dextrose RS, USP Lactose Monohydrate RS, USP Fructose RS, and USP Sucrose RS in Diluent

Sample solution: 0.5 mg/mL of Lactose Monohydrate in Diluent

Adsorbent: 0.25-mm layer of chromatographic silica gel

Application volume: 2 µL

Developing solvent system: Ethylene dichloride, glacial acetic acid, methanol, and water (10:5:3:2)

Spray reagent: 5 mg/mL of thymol in a mixture of alcohol and sulfuric acid (19:1)

Analysis

Samples: Standard solution A, Standard solution B, and Sample solution

Allow the spots to dry, and develop the plate in a paper-lined chromatographic chamber equilibrated with Developing solvent system for about 1 h prior to use. Allow the chromatogram to develop until the solvent front has moved about three-quarters of the length of the plate. Remove the plate from the chamber, dry in a current of warm air, and redevelop the plate in fresh Developing solvent system. Remove the plate from the chamber, mark the solvent front, and dry the plate in a current of warm air. Spray the plate evenly with Spray reagent. Heat the plate at 130° for 10 min.

System suitability: The test is not valid unless the chromatogram of Standard solution B shows four clearly discernible spots, disregarding any spots at the origin.

Acceptance criteria: The principal spot from the Sample solution corresponds in appearance and R, value to that from Standard solution A.,

3 IMPURITIES

RESIDUE ON IGNITION (281)

Analysis: A sample ignited at a temperature of 600 ± 50°

Acceptance criteria: NMT 0.1%

4 SPECIFIC TESTS

CLARITY AND COLOR OF SOLUTION

Sample solution: 1 g in 10 mL of boiling water

Analysis: The Sample solution is clear and nearly colorless. Determine the absorbance of this solution at a wavelength of 400 nm.

Acceptance criteria: The absorbance divided by the path length, in cm, is NMT 0.04.

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(NF 1-DEC-2024) MICROBIAL ENUMERATION TESTS (61), and TESTS FOR SPECIFIED MICROORGANISMS (62): The total aerobic microbial count does not exceed (NF 1-Dec-2024) 10² cfu/g, the total combined molds and yeasts count does not exceed 50 (NF 1-Dec-2024) cfu/g, and it meets the requirements of the test for absence of Escherichia coli.

OPTICAL ROTATION (781S), Procedures, Specific Rotation (NF 1-Dec-2024)

Sample solution: Dissolve 10 g by heating in 80 mL of water to 50°. Allow to cool, and add 0.2 mL of 6 N ammonium hydroxide. Allow to stand for 30 min, and dilute with water to 100 mL.

Acceptance criteria: +54.4° to +55.9°, calculated on the anhydrous basis, determined at 20°

ACIDITY OR ALKALINITY

Sample solution: Dissolve 6 g by heating in 25 mL of carbon dioxide-free water, cool, and add 0.3 mL of phenolphthalein TS.

Acceptance criteria: The solution is colorless, and NMT 0.4 mL of 0.1 N sodium hydroxide VS is required to produce a pink or red color.

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(NF 1-DEC-2024) LOSS ON DRYING (731).

Analysis: Dry a sample at 80° for 2 h.

Acceptance criteria

Monohydrate: NMT 0.5%

A (NF 1-Dec-2024) Monohydrate, modified: NMT 1.0%,

WATER DETERMINATION (921), Method I

Sample solution: Prepare a preparation containing Lactose Monohydrate in a mixture of methanol and formamide (2:1).

Acceptance criteria: 4.5%-5.5%

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PROTEIN AND LIGHT-ABSORBING IMPURITIES

(See Ultraviolet-Visible Spectroscopy (857).)

Sample solution: 1% (w/v)

Instrumental conditions

Mode: UV

Wavelength range: 210-300 nm (NF 1-Dec-2024)

Acceptance criteria: The absorbance divided by the path length, in centimeters, is NMT 0.25 in the range of 210-220 nm and is NMT 0.07 in the range of 270-300 nm.

5 ADDITIONAL REQUIREMENTS

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PACKAGING AND STORAGE: Preserve in tight containers. (NF 1-Dec-2024)

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A(NF 1-DEC-2024) LABELING: Where the labeling states the particle size distribution, it also indicates the d₁₀, d₅₀ and d₉₀ values and the range for each. For modified Lactose Monohydrate, also label it to indicate the method of modification. (NF 1-Dec-2024)

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USP REFERENCE STANDARDS (11).

USP Dextrose RS

USP Fructose RS

USP Lactose Monohydrate RS

USP Sucrose RS (NF 1-Dec-2024)