Note: Descriptions are shown in the official language in which they were submitted.
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This invention relates to a process for producing
aluminum hydroxide gels of pharmaceutical grade and particu-
larly a gel product which is free of or substantially free of
sodium salts.
Physicians are becoming increasingly aware of the
fact that sodium salts are counterindicated for persons having
hypertension and other cardio-vascular diseases and for persons
having renal impairment. For instance, such persons are
instructed to eliminate or severely curtail their consumption
of table salt. If such persons have gastrointestinal disorders
~hich are medicinally benefited by antacids, including aluminum
hydroxide gel, it is quite important that the gel not be con-
taminated by entrained sodium ions. A process which produces
aluminum hydroxide gel with no appreciable sodium ion content,
at a relatively low cost, is desirable.
Prior processes for producing aluminum hydroxide gel
have not been entirely satisfactory either because the process
produced a gel product which included an undesirably large
amount of sodium salts or because the process was too complex
and expensive to be commercially practicable. According to one
prior process, aluminum chloride is reacted with sodium carbon-
ate but this has required extensive flushing with wash water to
remove the sodium chloride. Another known process involves
reacting sodium aluminate with gaseous carbon dioxide but this
also involves using considerable wash water to reduce the
sodium ion content to an acceptable level.
The patent 3,066,012 to C.P. Wilson, Jr. et al is of
interest because it involves as a first step the reaction of an
aluminum sulfate solution with calcium carbonate to form a
basic aluminum sulfate sol, the second step of isolating the
sol, the third step of adding a sodium carbonate solution to
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form the alumina gel and the fourth step of washing out the
sodium salts and other soluble impurities. This process
involves a series of homogeneous step-wise reactions. The com-
mercial processes mentioned earlier above likewise involve
homogeneous reactions.
The process of the present invention involves a
heterogeneous reaction in water between a water soluble alumi-
num salt such as aluminum chloride and an alkaline earth carbon-
ate such as calcium carbonate. These reactants should be
selected or be properly purified to minimize sodium, iron and
other contaminants. The process can be carried out either as a
batch or as a continuous operation. A definite advantage of
the chemical reaction is that it may occur at ambient atmos-
pheric pressure and temperature. In either a batch or a con-
tinuous process reaction should be allowed to continue for at
least from 5 to 20 minutes.
Aluminum chloride is the preferred aluminum salt
reactant and it should constitute from 14 to 28% by weight of
the solution which is used. Calcium carbonate is the preferred
carbonate reactant and it should constitute from 4 to 10% by
weight of the aqueous slurry which is used. These two aqueous
preparations are combined in a relative amount so that the
reaction bath is maintained between about pH 4.7 and 5.5. This
will generally require the addition to 100 grams of calcium
carbonate of from 70 to 90 grams of aluminum chloride but it is
preferred that the reaction conditions be controlled on the
basis of the pH of the reaction.
The exact nature of the heterogeneous reaction is not
fully understood but it would appear that the fixing of the
carbonate by the solid calcium carbonate insures that carbonate
is present at the site of precipitation. This gives the alumi-
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num ion the immediate opportunjty of complexing with the carbon-
ate, which results in the most reactive and stable gel. This
stabilizing reaction is evidenced by a split of the carbonate
band in the 1400 - 1500 cm 1 region of the infrared spectrum.
The precipitated aluminum hydroxide gel is isolated
from the reaction bath and then washed to obtain it in a puri-
fied form. A unique feature of this process is that the gel
product which it produces is considerably more reactive than
gels produced by present day commercial processes. Because of
its exceptional acid consuming capacity it is particularly
valuable as a medicinal antacid.
Instead of aluminum chloride, other water soluble
aluminum salts may be substituted, such as for example the
sulfate or the nitrate, an amount being used to yield the same
aluminum content. Instead of calcium carbonate, other water
insoluble alkaline earth carbonates may be substituted, such as
for example magnesium carbonate, an amount being used to yield
the same carbonate ion content.
In a batch operation it is preferable, but not
essential, to add the aluminum salt in its water solution, to a
reactor vessel containing the alkaline earth carbonate in its
aqueous slurry. The vessel should be equipped with a stirrer
or other mechanical agitator and the aluminum salt solution
should gradually be added to it. Representative examples are
the following:
EXAMPLE 1
A total of 5000 ml. of water was charged to an agi-
tated reactor under ambient conditions and 210 gm. of U.S.P.
calcium carbonate was added and dispersed, thus forming a
slurry. Aluminum chloride solution (28% by weight) was then
fed to the slurry at a rate of 15 ml./min. until a total of
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490 ml. solution had been fed. The reaction bath assayed gener-
ally a pH 5.0 - 5.5 at the end of this addition. The resulting
aluminum hydroxide gel was isolated as by filtration and given
several water washes.
The 4% aluminum hydroxide gel suspension ~hich was
prepared from the gel slurry exhibited the following properties:
Assay, % Al 23 8.53
pH 6.70
Viscosity, cps 1 488
Acid consumption, ml.
O.l N HCl/gm. 25.2
CaO, % O. 44
Chlorides, % Q.04
EXAMPLE 2
In Example 1, magnesium carbonate was substituted for
the calcium carbonate and the product assayed as follows:
Assay, % A~ 23 6.98
pH 7.10
Viscosity, cps 1 084
Acid consumption, ml.
O.l N HCl/gm. 25.2
Mg(OH)2, % 0.38
C 1 , % _ _ _ _
EXAMPLE 3
In Example 1, aluminum sulfate was substituted For
the aluminum chloride.
EXAMPLE 4
This illustrates a continuous process in which the
reactants are constantly being added and intermixed with each
30 other and the resulting product is isolated.
A calcium carbonate slurry, maintained at a con-
sistency to contain 5% CaC03 by weight, and an aluminum
chloride solution, maintained at a consistency to contain 14%
by weight AlC13, were fed simultaneously to an agitated reactor
at ambient pressure and temperature. The calcium carbonate
feed rate was about 1 gal/min and the aluminum chloride feed
was maintained by a pH controller-reactor system to give a
reactor pH around 5Ø Overflow from the reactor, containing
the aluminum hydroxide gel slurry, was filtered and washed on a
rotary filter.
The 4% aluminum hydroxide gel suspension prepared
from this partlcular reaction showed the following properties:
Assay, % A1203 8.09
pH 6.50
Viscosity, cps 420
Acid consumption, ml.
0.1 N HCl/gm. 26.2
CaO, % 0.86
Chlorides, % 0.15
EXAMPLE 5
In Example 4, magnesium carbonate was substituted for
the calcium carbonate and the product assayed as follows:
Assay, % A1203
pH 7.10
Viscosity, cps 1358
Acid consumption, ml.
0.1 N HCl/gm. 24.7
Mg(OH)2, % 0.44
C 1 , %
EXAMPLE 6
In any of the above examples the relative amounts of
the reactants can be varied within the limits of this in-
vention.
The foregoing examples are to be construed as illus-
trations of this invention and are not considered to be limi-
tations thereof.
EXAMPLE 7
The aluminum hydroxide gel obtained in any of
Examples 1-4 is mixed with pharmaceutically acceptable excipi-
ents to form a pharmaceutical composition in oral dosage form.
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