Lactose

(Lactose Monohydrate, Ph Eur monograph 0187)

C₁₂H₂₂O₁₁,H₂O    360.3    10039-26-6

Excipient.

Ph Eur

O-β-D-Galactopyranosyl-(1→4)-α-D-glucopyranose monohydrate.

White or almost white, crystalline powder.

Freely but slowly soluble in water, practically insoluble in ethanol (96 per cent).

First identification   A, D.

Second identification   B, C, D.

A. Infrared absorption spectrophotometry (2.2.24).

Comparison   lactose CRS.

B. Thin-layer chromatography (2.2.27).

Solvent mixture  water R, methanol R (2:3 V/V).

Test solution  Dissolve 10 mg of the substance to be examined in the solvent mixture and dilute to 20 mL with the solvent mixture.

Reference solution (a)  Dissolve 10 mg of lactose CRS in the solvent mixture and dilute to 20 mL with the solvent mixture.

Reference solution (b)  Dissolve 10 mg of fructose CRS, 10 mg of glucose CRS, 10 mg of lactose CRS and 10 mg of sucrose CRS in the solvent mixture and dilute to 20 mL with the solvent mixture.

Plate   TLC silica gel G plate R.

Mobile phase  water R, methanol R, glacial acetic acid R, ethylene chloride R (10:15:25:50 V/V/V/V); measure the volumes accurately, as a slight excess of water produces cloudiness.

Application  2 µL; thoroughly dry the points of application.

Development A  Over a path of 15 cm.

Drying A  In a current of warm air.

Development B  Immediately, over a path of 15 cm, after renewing the mobile phase.

Drying B  In a current of warm air.

Detection  Spray with a solution of 0.5 g of thymol R in a mixture of 5 mL of sulfuric acid R and 95 mL of ethanol (96 per cent) R; heat at 130 °C for 10 min.

System suitability  Reference solution (b):

• — the chromatogram shows 4 clearly separated spots.

Results  The principal spot in the chromatogram obtained with the test solution is similar in position, colour and size to the principal spot in the chromatogram obtained with reference solution (a).

C. Dissolve 0.25 g in 5 mL of water R. Add 5 mL of ammonia R and heat in a water-bath at 80 °C for 10 min. A red colour develops.

D. Water (see Tests).

The solution is clear (2.2.1) and not more intensely coloured than reference solution BY₇ (2.2.2, Method II).

Dissolve 1.0 g in boiling water R and dilute to 10 mL with the same solvent.

Dissolve 6.0 g by heating in 25 mL of carbon dioxide-free water R, cool and add 0.3 mL of phenolphthalein solution R1. The solution is colourless. Not more than 0.4 mL of 0.1 M sodium hydroxide is required to change the colour of the indicator to pink or red.

+ 54.4 to + 55.9 (anhydrous substance).

Dissolve 10.0 g in 80 mL of water R, heating to 50 °C. Allow to cool and add 0.2 mL of dilute ammonia R1. Allow to stand for 30 min and dilute to 100.0 mL with water R.

Test solution (a)  Dissolve 1.0 g in boiling water R and dilute to 10.0 mL with the same solvent.

Test solution (b)  Dilute 1.0 mL of test solution (a) to 10.0 mL with water R.

Spectral range  400 nm for test solution (a) and 210-300 nm for test solution (b).

• — at 400 nm: maximum 0.04 for test solution (a);

• — from 210 nm to 220 nm: maximum 0.25 for test solution (b);

• — from 270 nm to 300 nm: maximum 0.07 for test solution (b).

Maximum 5 ppm.

Dissolve 4.0 g in water R with warming, add 1 mL of 0.1 M hydrochloric acid and dilute to 20 mL with water R. 12 mL of the solution complies with test A. Prepare the reference solution using lead standard solution (1 ppm Pb) R.

4.5 per cent to 5.5 per cent, determined on 0.50 g, using a mixture of 1 volume of formamide R and 2 volumes of methanol R as the solvent.

Maximum 0.1 per cent, determined on 1.0 g.

TAMC: acceptance criterion 10² CFU/g (2.6.12).

Absence of Escherichia coli (2.6.13).

In an airtight container.

This section provides information on characteristics that are recognised as being relevant control parameters for one or more functions of the substance when used as an excipient ( see chapter 5.15 ). This section is a non-mandatory part of the monograph and it is not necessary to verify the characteristics to demonstrate compliance. Control of these characteristics can however contribute to the quality of a medicinal product by improving the consistency of the manufacturing process and the performance of the medicinal product during use. Where control methods are cited, they are recognised as being suitable for the purpose, but other methods can also be used. Wherever results for a particular characteristic are reported, the control method must be indicated.

The following characteristics may be relevant for lactose monohydrate used as a filler/diluent in solid dosage forms (compressed and powder).

Determine the bulk density and the tapped density. Calculate the Hausner Index using the following expression:

V 0	=	volume of bulk substance;
V f	=	volume of tapped substance.

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