Hydrated Aluminium Hydroxide for Adsorption

(Ph. Eur. monograph 1664)

DEFINITION

Content

90.0 per cent to 110.0 per cent of the content of aluminium stated on the label.

NOTE: shake the gel vigorously for at least 30 s immediately before examining.

CHARACTERS

Appearance

White or almost white, translucent, viscous, colloidal gel. A supernatant may be formed upon standing.

Solubility

A clear or almost clear solution is obtained with alkali hydroxide solutions and mineral acids.

IDENTIFICATION

Solution S (see Tests) gives the reaction of aluminium.

To 10 mL of solution S add about 0.5 mL of dilute hydrochloric acid R and about 0.5 mL of thioacetamide reagent R. No precipitate is formed. Add dropwise 5 mL of dilute sodium hydroxide solution R. Allow to stand for 1 h. A gelatinous white precipitate is formed which dissolves upon addition of 5 mL of dilute sodium hydroxide solution R. Gradually add 5 mL of ammonium chloride solution R and allow to stand for 30 min. The gelatinous white precipitate is re-formed.

TESTS

Solution S

Add 1 g to 4 mL of hydrochloric acid R. Heat at 60 °C for 1 h, cool, dilute to 50 mL with distilled water R and filter if necessary.

pH (2.2.3)

5.5 to 8.5.

Adsorption power

Dilute the substance to be examined with distilled water R to obtain an aluminium concentration of 5 mg/mL. Prepare bovine albumin R solutions with the following concentrations of bovine albumin: 0.5 mg/mL, 1 mg/mL, 2 mg/mL, 3 mg/mL, 5 mg/mL and 10 mg/mL. If necessary, adjust the gel and the bovine albumin R solutions to pH 6.0 with dilute hydrochloric acid R or dilute sodium hydroxide solution R.

For adsorption, mix 1 part of the diluted gel with 4 parts of each of the solutions of bovine albumin R and allow to stand at room temperature for 1 h.

During this time shake the mixture vigorously at least 5 times. Centrifuge or filter through a non- protein-retaining filter. Immediately determine the protein content (2.5.33, Method 2) of either the supernatant or the filtrate.

It complies with the test if no bovine albumin is detectable in the supernatant or filtrate of the 2 mg/mL bovine albumin R solution (maximum level of adsorption) and in the supernatant or filtrate of bovine albumin R solutions of lower concentrations. Solutions containing 3 mg/mL, 5 mg/mL and 10 mg/mL bovine albumin R may show bovine albumin in the supernatant or filtrate, proportional to the amount of bovine albumin in the solutions.

Sedimentation

If necessary, adjust the substance to be examined to pH 6.0 using dilute hydrochloric acid R or dilute sodium hydroxide solution R. Dilute with distilled water R to obtain an aluminium concentration of approximately 5 mg/mL. If the aluminium content of the substance to be examined is lower than 5 mg/mL, adjust to pH 6.0 and dilute with a 9 g/L solution of sodium chloride R to obtain an aluminium concentration of about 1 mg/mL. After shaking for at least 30 s, place 25 mL of the preparation in a 25 mL graduated cylinder and allow to stand for 24 h.

It complies with the test if the volume of the clear supernatant is less than 5 mL for the gel with an aluminium content of about 5 mg/mL.

It complies with the test if the volume of the clear supernatant is less than 20 mL for the gel with an aluminium content of about 1 mg/mL.

Chlorides (2.4.4)

Maximum 0.33 per cent.

Dissolve 0.5 g in 10 mL of dilute nitric acid R and dilute to 500 mL with water R.

Nitrates

Maximum 100 ppm.

Place 5 g in a test-tube immersed in ice-water, add 0.4 mL of a 100 g/L solution of potassium chloride R, 0.1 mL of diphenylamine solution R and, dropwise with shaking, 5 mL of sulfuric acid R. Transfer the tube to a water-bath at 50 °C.

After 15 min, any blue colour in the solution is not more intense than that in a standard prepared at the same time and in the same manner using 5 mL of nitrate standard solution (100 ppm NO₃) R.

Sulfates (2.4.13)

Maximum 0.5 per cent.

Dilute 2 mL of solution S to 20 mL with water R.

Ammonium (2.4.1, Method B)

Maximum 50 ppm, determined on 1.0 g.

Prepare the standard using 0.5 mL of ammonium standard solution (100 ppm NH4) R.

Arsenic (2.4.2, Method A)

Maximum 1 ppm, determined on 1 g.

Iron (2.4.9)

Maximum 15 ppm, determined on 0.67 g.

Bacterial endotoxins (2.6.14)

Less than 5 IU of endotoxin per milligram of aluminium, if intended for use in the manufacture of an adsorbed product without a further appropriate procedure for the removal of bacterial endotoxins.

ASSAY

Dissolve 2.50 g in 10 mL of hydrochloric acid R, heating for 30 min at 100 °C on a water-bath. Cool and dilute to 20 mL with water R. To 10 mL of the solution, add concentrated ammonia R until a precipitate is obtained. Add the smallest quantity of hydrochloric acid R needed to dissolve the precipitate and dilute to 20 mL with water R. Carry out the complexometric titration of aluminium (2.5.11). Carry out a blank titration.

STORAGE

At a temperature not exceeding 30 °C. Do not allow to freeze. If the substance is sterile, store in a sterile, airtight, tamper- evident container.

LABELLING

The label states the declared content of aluminium.