Lactose Monohydrate USP Monograph USP 44 - NF39

Here you find Lactose Monohydrate USP Monograph USP 44 - NF39, Definition, Identification, Assay, Impurities, Specific Tests, Additional.

Lactose Monohydrate USP

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.

DEFINITION

Lactose Monohydrate is the monohydrate of O-β-D-galactopyranosyl-(1→4)-α-D-glucopyranose.

[NOTE—Lactose Monohydrate may be modified as to its physical characteristics. It may contain varying proportions of amorphous lactose.]

IDENTIFICATION 

Change to read:

• A. ▲SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K▲ (CN 1-May-2020)

• ◆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 RF value to that from Standard solution A.

IMPURITIES

• RESIDUE ON IGNITION (281)

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

Acceptance criteria: NMT 0.1%

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 wavelengthof 400 nm.

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

• ◆ MICROBIAL ENUMERATION TESTS (61) and TESTS FOR SPECIFIED MICROORGANISMS (62): The total aerobic microbial count does not exceed 1 × 102 cfu/g, the total combined molds and yeasts count does not exceed 5 × 101 cfu/g, and it meets the requirements of the test for absence of Escherichia coli.◆

• OPTICAL ROTATION, Specific Rotation (781S)

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°

IMPURITIES

RESIDUE ON IGNITION (281)

Analysis: A sample ignited at a temperature of 600 ± 50°Acceptance criteria: NMT 0.1%

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 length, in cm, is NMT 0.04.

• ◆ MICROBIAL ENUMERATION TESTS (61) and TESTS FOR SPECIFIED MICROORGANISMS á62ñ: The total aerobic microbial count does not exceed 1 × 102 cfu/g, the total combined molds and yeasts count does not exceed 5 × 101 cfu/g, and it meets the requirements of the test for absence of Escherichia coli.◆

• OPTICAL ROTATION, Specific Rotation (781S)

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.

◆ LOSS ON DRYING á731ñ

Analysis: Dry a sample at 80° for 2 h. Acceptance criteria Monohydrate: NMT 0.5%Monohydrate, modified: NMT 1.0%◆

WATER DETERMINATION, Method I (921)

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

Acceptance criteria: 4.5%–5.5%

PROTEIN AND LIGHT-ABSORBING IMPURITIES

(See Ultraviolet-Visible Spectroscopy á857ñ.)

Sample solution: 1% (w/v)

Analysis: Measure the light absorption of the sample solution in the range of 210–300 nm.

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

ADDITIONAL REQUIREMENTS

◆ PACKAGING AND STORAGE: Preserve in tight containers.

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.

USP REFERENCE STANDARDS (11)

USP Dextrose RS

USP Fructose RS

USP Lactose Monohydrate RS

USP Sucrose RS