Note: Descriptions are shown in the official language in which they were submitted.
lns(~ s
Background of the Invention
1. Field of the Invention
This invention relates to a process for producing
a pharmaceutical grade of barium sulphate.
2. Description of the Prior Art
Pharmaceutical barium sulphate is widely used as `~
a radiopaque medium in the gastrointesinal tract, It is a
fine, white, odourless, tasteless bulky powder which is
practically insoluble in water, in organic solvents and
in solutions of acids and of alkalies. It does, however,
exhibit some solubility in hot concentrated sulphuric acid.
; While this extremely inert quality of barium sulPhate makes -~
it ideal as a radiopaque mediu~it has also in the past
created great problems in the production of barium sulphate
of pharmaceutical purity.
s~ The chemical specifications of pharmaceutical
' barium sulPhate are precisely known. The USP specifications
can be summarized as follows:
Test USP Specifications
Heavy Metals (as Pb) 0.0010% maximum
Sulphide To pass test
, Arsenic 0.0001% maximum (As203)
Acid Soluble Substance 0.3% maximum
Soluble Barium Salts To pass test
Phosphate To pass test
Acid or Alkalinity To pass test
The usual commercial procedure now being used
is the Mallinckrodt process in which finely divided barite
ore is taken into solution by means of an acid and then
precipitating barium sulphate. Because of the inertness of
barlum sulphate,this is a very difficult and expensive procedure.
Even the precipitate formed still contains many impurities
and must be sub~ected to a number of additional purification
steps including acid leaching.
It is the object of the present invention to
provide a simpler and less expensive process for producing
pharmaceutical barium sulphate.
Summary of the Invention
In accordance with the present invention, it has
surprisingly been found that a greatly simplified procedure
for producing pharmaceutical barium sulphate is possible by
commencing with a naturally occurring barite ore which contains
individual crys~als of substantially pure barium sulphate.
In other words, the barium ~ulphate within the individual -
crystals is of pharmaceutical purity.
According to thè inventive prccess, this naturally
occurring barite ore containing individual crystals of
~ sub~tantially pure barium sulphate,together with gangue minerals,
:~ i9 first ground to form a finely divided particulate ore
~l material. This finely divided ore is then passed through a
high intensity wet magnetic separator to remove magnetic
particles, leaving a non-magnetic fraction containing barium
-~ sulfate and low specific gravity minerals. The non-magnetic
.. ,~ . .
~,
fraction is subjected to gravity separation and from this
gravity separation a substantially pure barium sulphate fraction
i is obtained. This barium sulphate fraction is then subjected
,~ to leac~ing with sulphuric acid to remove any remaining acid
sOluble impurities and is washed to form a final pharmaceutical
' barium sulphate.
f
The barium sulphate obtained by this procedure
; 30 easily meets all of the USP specifications.
;
f
-- 2
S
DescriPtion of Preferred Embodimen~s
Preparation of Ore
The ore contains, in addition to the individual
crystalls of substantially pure barium sulphate, many other
gangue! minerals. These gangue minerals typically include
iron carbonate, iron oxides, silica and iron silicates.
One example of a typical ore analysis is as follows:
BaS04 74.4%
FeC03 18.6%
SiO2 5.6% ;
Miscellaneous 1.4%
However, it will be appreciated that the gangue minerals
and their proportions can vary greatly in relation to the barium
sulphate and the main consideration is that the lower the amount
of barium sulpbate present in the ore~ the greater amount of ore
; that will hsve to be prepared and processed through the wet
I magnetic ~eparator to obtain a given amount of barium sulphate.
i The ore a~ obtained fxom the mine is preferably sub-
jected to an initial primary grinding with care being taken to
keep the production of fine particle~ to a minimum. This can
conveniently be done, for instance, by means of a ~aw crusher
followed by a gyratory crusher or other means to reduce the
i particles to a convenient working size of, for instance, 1/2 inch.
These ore particles are then subjected to a secondary
grinding, for instance in a ball mill, rod mill or hammer mill,
to produce finely divided particles suitable for feeding to
a high intensity wet magnetic separator. Preferably the
separator feed has a particle size of -35 mesh ~U.S. sieve)
with care being taken to avoid excessive fines.
The size of the particles can be varied depending
on the n~tture of the ore deposits with the concept being to
- 3 -
form particles among which there will be a large number of
individual particles of substantially pure barium sulphate,
Magnetic Separation
The suitably ground ore is subjected to high intensity
wet 1nagnetic separation and a variety of high intensity wet
magnetic separators are known. A particularly suitable machine
is the Jones separator.
The ground ore can be passed through the separator
one or more times to remove as much of the magnetic particles
a~ posslble. The ore will contain particles of varying
s degrees of magnetic susceptability and, for instance, there
may be combined particles of iron carbonate and silica where
the combined particle, due to its iron carbonate content, is
sufficiently magnetic to remove the entire particle. It is
also sometimes desirable to size the feed to the separator
since better recults may be obtained if the feed does not
contain particles of too greatly varying sizes. For instance,
the ore feed to the separator could be divided into three
different size ranges for feeding, e.g. -10 ~ 35; -35 + 65;
-65 + 100 mesh.
During the magnetic separation, the bulk of the
magnetic minerals or combined particles that as a whole
e~hibit some magnetic susceptability are removed. The non-
magnetic fraction at this stage contains primarily barium --
' sulfate and the lighter specific gravity minerals such as
~ quartz, as well as other contaminants such as lead, zinc, etc.
i Gravity Separation
Much of the undesirable material remaining in the
non-magnetic fraction obtained from the magnetic separator
can be removed by gravity separation. A variety of gravity
separators are known and a highly useful one for this purpose
- 4 -
~ iO;~35
is the wet shaking table. Once again, it may be desirable to
brealc the non-magnetic fraction up into quite restricted `
size ranges by screening prior to the gravity separation.
This tends to give a better separation.
The "heavys" end of the table contains predominantly
barium sulfate while the "lights" end contains the gangue.
There may be a fraction removed in between these that, on
completion of the leaching process, does not meet pharmaceutical
specifications, but it has been found that this fraction
normally meets the requirements for a commercial product
known as "Ground White Barite".
Leachin~
The purpose of the leaching step is to eliminate
any remaining soluble impurities f such as soluble barium
salt~ etc. which must be eliminated in order to pass the
specified test. In order to obtain a product meeting USP
specifications, it has been found that the leaching must
be conducted with sulphuric acid.
convenient technique for this is a counter-current
three-stage leach starting with 25% commercial sulphuric acid
; ~ith commercial tap water and three washing steps. Of course,
these steps can be greatly varied depending on the concentration
of the acid used, economics, grade of water, etc.
The product obtained from the leaching step is
1 filtered and washed and can either be made up in plastic bags --
in the ~orm of pre~Mixed dosage units or it may be dried
screened and packaged as a dry powder.
EXAMP~E
An ore sample was obtained from a mine located at
Brookfield, Nova Scotia, Canada. This ore had the following
analysis.
-- 5 --
lO~iOZ35
BaS04
FeC03 18.6%
SiO2 5.6%
Miscellaneous 1.4Z
The ore was reduced in size by means of a jaw crusher
to form particles having a dimension of about 1/2 inch. These ~
particles were then passed through a hammer mill to produce a -
flnely divided ore having particles of -35 mesh.
This finely divided ore was passed through a "Standard
Laboratory Jones High Intensity Wet Magnetic Separator" with a
maximum amperage to coils of 40 amperes to obtain 44% by weight
of a magnetics fraction and 56% by weight of a non-magnetics
fraction. The non-magnetic fraction was screened into the
following ize fractions:
-35 + 60 mesh
! -60 + 150 mesh,~ -150 mesh
Each of the above fractions was subjected to gravity
separation on a wet table no. 11099 ava~lable from Deister
Concentrating Company Inc. and three cuts were made of the
heavys product. In other words, the heavys product was
'1
removed from the wet table as three separate fractions. The
weight distribution of these various fractions is shown in -
3~
-~ Table 1 below:
~ TABLE 1
. _
~; ~ Particle Size -35 + 60 -80 + 150 -150
1 __
, ~ Wet Table Cut C-l C-2 C-3 C-l C-2 C-3 C-l C~2 C-3
% Wt. BaS04
Based on 12.0 4.7 1.91.7 0.9 0.9 2.0 2.6 1.3
Orig. Feed
~ 30 Total BaS04
i (% Wt.) 28.0%
, - 6 -
l~()Z35
The various fractions obtained were then subjected
to leaching with 20~ sulphllric acid solutions using a coun~er
current four stage procedure with analytical grade and commercial
grade sulfuric acid and either tap water or distilled water.
~ach leaching stage was of 30 minutes duration and the leaching
procedures used on the various fractions are set out in Table
2 below:
TABLE 2
Product No.Source Relevant Process Differences
117 Analytical grade ~2S04 and
118 All C-l's distilled water wa~h. All
119 leaching on -150 mesh.
131 C-l, C-2, Analytical grade H2S04 and
132 C-3 tap water wash. Leaching on
133 (-35+60) finely ground.
; 134 C-l, C-2 Analytical grade H2S04 and
135 C-3 tap water wash. Leaching on
136 (-60+150) finely ground.
137 C-l, C-2, Analytical grade H2S04 and
~i 138 C-3 tap water wash. Leaching on
139 (-150) finely ground.
145 C-l Commercial grade acid and tap
146 (-35+60) water. Leaching on -150 mesh.
147 C-l Three stage commercial grade.
148 (-35+60) Last stage analytical with top
water wash. Leaching on -150
mesh.
The above samples were submitted to an independent
testing laboratory for the prescribed tests required under
the USP specifications. The results of these tests are
given in Table 3 below:
:
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