Note: Descriptions are shown in the official language in which they were submitted.
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This invention relates to a process for preparing spray-
dried water-soluble vitamin powders which are directly com-
pressible into tablets, and to the powders prepared thereby.
Particularly useful water-soluble vitamins are ascorbic
acid, sodium ascorbate, and calcium ascorbate.
U.S. Patent 3,293,132 describes a continuous process for
making a vitamin C powder by spray drying. The process
involves spray drying from 75 to 95 parts by weight of
ascorbic acid, from 5 to 25 parts by weight of a carbo-
hydrate, and from 0.5 to 5 parts by weight of a film-
producing hydrophilic, organic colloid material such as
gelatin, water-soluble derivatives of casein, water-soluble
gums, and water-soluble derivatives of cellulose. Although
the process is continuous, a lubricant is not one of the
spray dried components. Instead, the lubricant is blended
into the spray-dried powder after spray drying.
Consequently, the powder taken directly from the spray dryer
cannot be directly compressed into tablets. Moreover, the
powder disclosed in this patent is l~kely to discolour at
use conditions.
The present invention provides a process for preparing free
flowing powders, which contain a water-soluble vitamin and
which are directly compressible into a tablet, which process
comprises spray drying effective amounts of (a) an aqueous
slurry of a water-soluble vitamin and a binder; (b~ a
lubricant; and preferably (c) an adsorbent. The process is
unique because the lubricant is mixed with all of the other
components during the spray-drying.
The invention also relates to the powders prepared by this
process. The powders are directly compressible into tablets
without needing the addition of other excipients, and are
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unique because they do not demix. They are also color
stable tablets which have acceptable disintegration times
and hardness.
DESCRIPTION OF THE PREFERRED EMBODIMENT
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The powders of this invention which contain a water-soluble
vitamin are prepared by spray drying an aqueous slurry of
water-soluble vitamin and a binder in the presence of a
lubricant and preferably an adsorbent. In general, any
water-soluble vitamin can be used in the process. Specific
examples include ascorbic acid, sodium ascorbate, calcium
ascorbate, niacin, riboflavin, pyridoxine, calcium d-panto-
thenate, thiamine hydrochloride, thiamine nitrate,
pantothenic acid, folic acid, and biotin. Of more interest,
however, are ascorbic acid, sodium ascorbate, and calcium
ascorbate. Natural sources of these water-soluble vitamins,
such as rosehips, may also be used, preferably in minor
amounts.
Typical binders (for example, see U~S. Patent 3,293,132 at
column 3, lines 29 54) that can be used include proteins
such as gelatin, water-soluble derivatives oE casein, e.g.,
sodium caseinate, and the like; water-soluble gums such as
gum acacia, gum karaya, gum ghatti, tragacanth, and the
like; cellulose, and water-soluble derivatives of cellulose
such as methylcellulose, hydroxyethyl cellulose, sodium
carboxymethylcellulose, and the like. For this purpose, use
may furthermore be rnade of certain polyvinyl resins such as,
for example, polyvinyl alcohol, polyvinyl pyrrolidine and
the like. Preferably used with ascorbic acid, sodium
ascorbate, and calcium ascorbate are microcrystalline
cellulose, and mixtures of microcrystalline cellulose and
hydroxypropylmethylcellulose.
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To prepare the aqueous slurry, the water-soluble vitamin and
binder are added to enough water -to make a finished feed
slurry having about 10 to 90 percent solids by weight, and,
preferably, about 50 to 75 percent by weight solids.
The aqueous slurry containing the water-soluble vitamin and
binder is preferably spray dried in the presence of an
adsorbent such as those disclosed ln U.S. Patent 3,914,430
a-t column 3, lines 43-68. ~referably used as the adsorbent
is silicon dioxide, particularly silicon dioxide having a
particle size of from 0.1 to 10.0 microns.
As was indicated previously, a lubricant is an essential
component of the powder and may be incorporated into the
powder product by spray drying the aqueous slurry of water-
soluble vitamin and microcrystalline cellulose in the
presence of the lubricant in addition to the adsorbent.
However, the preblending step to mix the absorbent and
lubricant can be eliminated by adding the lubricant to the
slurry and spray drying the slurry plus lubricant in the
presence of only the adsorbent. Preferably used as the
lubricant are stearic acid, magnesium stearate and mixtures
thereof. However, other stearic acids salts may be used
such as calcium stearate. Also, there can be used wax-like
materials, for instance, wax-like saturated fatty acids,
wax-like mixtures containing two or more saturated fatty
acids or wax-like hydrogenated glyceride, in admixture with
a metallic stearate and/or titanium dioxide such as are
disclosed in U.S. Patent 3,396,226 (column 3, lines 29-55).
Additional excipients may also be used in preparing the
subject powders. Although not used on a preferred basis
because of nutritional factors, the subject powders may also
contain carboxyhydrates such as sugars including lactose,
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sucrose, maltose, glucose, mannose, Eructose, arabinose, and
the like; non-sugars such as pectin, starch, and the like
and closely related polyhydric alcohols containing from 4 to
6 hydroxyl radicals such as mannitol, dulcitol, sorbitol,
and the like.
The components described herein are used in effective
amounts. Those skilled in the art can determine what
amounts are to be used based upon their own experience and
the examples set forth herein. However, when ascorbic acid,
sodium ascorbate, and calcium ascorbate are used as the
water-soluble vitamin, the components described herein are
added in amounts such that the final powder formed will
contain at least 80 (preferably at least 90) percent by
weight of the water-soluble vitamin, less than 15
(preferably less than 9) percent by weight of binder, 0.2 to
2 percent by weight of adsorbent, and 0.2 to 5 percent by
weight of lubricant and less than 3 percent of other
excipients. Although these amounts may also be effective
for other water-soluble vitamins, those skilled in the art
may discover better proportions with them and for specific
purposes.
Any suitable spray drier may be used to prepare the powders
of this invention such as vertical spray drier
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equipped with a means of making droplets, such as a rotary
atomizer operated between 10,000 and 35,000 rpm, preferably
18,000 to 25,000 rpm for a small dryer or suitable atomizer
nozzles (such as high pressure, two- and three-fluid). The
inlet temperature is maintained at 190 C to 200 C and the
outlet temperature is a function of the inlet temperature
and flow rate, generally between 90 C to 100 C. From 0.5
to 2.5 percent by weight, based on the weight of the dry
powder of silicon dioxide and from 0.5 to 5.0 percent of the
lubricant is added to the spray drier chamber, pre~erably at
a point of negative pressure. The aqueous slurry of water-
soluble vitamin and microcrystalline cellulose is then spray
dried to form a frae-flowing, nonagglomerated powder.
Tablets from the powder are made by conventional
methods. Useful tabletting aids are disclosed in Pharmaceu-
tical Technology, July, 1980, pages 27-35, and 62.
The examples which follow will provide more
details regarding how to practice the invention. In the
examples, unless otherwise stated, all parts are by weight
and all temperatures are in degrees centigrade.
EXAMPLE 1:
An aqueous slurry containing 60 percent by weight
solids was formed by adding 9286 parts of ascorbic acid and
714 parts of microcrystalline cellulose to water beld in a
stainless steel jacketed tank equipped with a turbine
agitator. The aqueous slurry was sprayed into a four foot
diameter vertical spray drier through a rotary atomizer at
20,000 to 23,000 revolutions per minute. About 1.0 percent
3Q by weight of silicon dioxide (sold under the trade name
AEROSIL 200*), and 1.0 percent by weight of magnesium
stearate were added into the drying chamber at a point of
negative pressure.
The resulting spray-dried powder contained:
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Component Percen~ by Weight Based on
the Weight of the Dry Powder
Ascorbic acid 90.0
5 Microcrystalline cellulose 7.0
Silicon dioxide 1.0
Magnesium stearate 1.0
Moisture 1.0
The particle size of the powder was such that 15
to 40 percent of the powder was retained on a 200 mesh
screen, 40 to 65 percent of the powder was retained on a 325
mesh screen, and 5 to 30 percent of the powder was able to
pass through a 325 mesh screen.
Tablets were made on a single rotary tablet press
at 30 revolutions per minute. The resulting tablets had a
hardness of 14.0 (SCU), a friability percent of 3.90 which
was measured as loss after 120 revolutions in a Vandercamp
friabilator, and a disintegrating time of 3.9 minutes in
water at 37 C in a Vandercamp disintegration/dissolution
tester.
EXAMPLE 2
A suspension was made in a stainless steel
jacketed tank equipped with an agitator by adding water to
I0~2 parts of hydroxypropylmethylcellulose such that the
resulting suspension had a solids weight of 7.5 percent by
weight. The suspension was heated to about 80 C and then
cold water was added in an amount such that the suspension
~; ~ 30 had 2.25 percent solids. Then 5572 parts of ascorbic acid
and 274 parts of microcrystalline cellulose were added.
The resulting slurry was sprayed into a nine foot
diameter vertical spray driar through a rotary atomizer at
10,000 to 14,000 revolutions per minute. About 1.0 percent
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by weight of silicon dioxide (sold under the trade name
AEROSIL 200) and 2.0 percent by weight of stearic acid were
added into the drying chamber at a point of negative
pressure.
The resulting yield was 5882 parts of a spray
dried powder which contained:
Component Percent by Weight Based on
the Weight of the Dry Powder
10 Ascorbic acid 90.5
Microcrystalline cellulose 4.6
Hydroxypropylmethylcellulose 1.4
Silicon dioxide 1.0
Stearic acid 2.0
15 Moisture 0.5
The resulting tablets had a hardness of 15.0
(SCU), a friability of 2.14 percent, and a disintegration
time of 21 minutes.
EXAMPLE 3
A suspension was made in a stainless steel
jacketed tank equipped with an agitator by adding water to
200 parts of hydroxypropylmethylcellulose such that the
resulting suspension had a solids weight of 6.7 percent by
weight. The suspension was heated to about 80 C, and then
cold water was added in an amount such that the suspension
had 2.32 percent solids. Then 433 parts of microcrystalline
cellulose and 200 parts of stearic acid were added.
The resulting slurry was sprayed through a two-
fluid nozzle (2.9 mm diameter, 39 peig) from the bottom of a
four-foot diameter spray drier into a counter current air
stream. About 1.0 percent by weight of silicon dioxide was
added into the drying chamber at a point of negative
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pressure.
The resulting powder contained:
Component Percent by Weight Based on
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the Weight of the Dry Powder
Ascorbic acid 90.5
Microcrystalline cellulose 4.2
Hydroxypropylmethylcellulose 1.9
10 Stearic acid 1.9
Silicon dioxide 1.0
Moisture 0 5
The resulting tablets had hardness of 14.1 (SCU),
a friability of 2.15 percent, and a disintegration time of
17 minutes.
EXAMPLE 4
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A suspension was made in a stainless steel tank
equipped with an agitator by adding hot water to 195 parts
of hydroxypropylmethylcellulose such that the resulting
suspension had a solids weight of 9.75 percent by weight.
The suspension was heated on a hot plate to about 80 C and
then cold water was added in an amount such that the
25 suspension had 3.17 percent solids. Then 9290 parts of
sodium ascorbate and 515 parts of microcrystalline cellulose
were added, followed by 800 parts additional water.
The resulting slurry was sprayed into a four foot
diameter vertical spray drier through a rotary atomizer at
30 about 23,000 revolutions per minute. About 1.0 percent by
weight of silicon dioxide (sold under the trade name Syloid
244FP*) and 2.0 percent by weight of stearic acid were added
into the drying chamber at a point of negative pressure.
The resulting yield was 10,~00 parts of a spray
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dried powder which contained:
Component Percent by Weight Based on
the Weight of the Dry Powder
Sodium Ascorbic 87.6
Microcrystalline cellulose 4.9
Hydroxypropylmethylcellulose 1.8
Silicon dioxide l.0
Stearic acid 2.0
Moisture 3 0
The xesulting tablets had a hardness of 13.6
(SCU), a friability of 0.44 percent, and a disintegration
time of 28 minutes.
EXAMPLE 5
A suspension was made in a stainless steel tank
equipped with an agitator by adding hot water to 195 parts
of hydroxypropylmethylcellulose such that the resulting
suspension had a solids weight of 7.9 percent by weight.
The suspension was heated to about 80 C on a hot plate and
then cold water was added in an amount such that the
suspension had 2.8 percent solids. Then 9290 parts of
calcium ascorbate and 515 parts of microcrystalline
cellulose were added, followed by an additional 600 parts
water.
The resulting slurry was sprayed into a four foot
diameter vertical spray drier through a rotary atomizer at
23,000 revolutions per minute. About 1.0 percent by weight
of silicon dioxide (sold under the trade name Syloid 244FP)
and 2.0 percent by weight of stearic acid were added into
the drying chamber at a point of negative pressure.
The resulting yield was 10,532 parts of a spray
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dried powder which contained:
Component Percent by Weight Based on
the Weight of the Dry Powder
Calcium ascorbate 88.2
Microcrystalline cellulose4.9
Hydroxypropylmethylcellulose 1.9
Silicon dioxide 1.0
10 Stearic acid 2.0
Moisture 2.0
The resulting tablets had a hardness of 11.9
(SCU), a friability of 0.69 percent, and a disintegration
time of > 45 minutes.
These examples show that powders containing water-
soluble vitamins can be prepa~ed by spray drying the
components, including the lubricant, by a continuous process
to make a directly compressible powder that does not demix.
The tablets formed with the powders have acceptable
hardness, disintegration times, and color stability.
Comparison Example
Following the procedure of Example 3, a spraydried
powder (Powder #1) was prepared having the following
composition:
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ComponentPercent by Weight Based
upon the Dry Powder _
Ascorbic Acid 90.1
5 Microcrystalline cellulose 5.0
Adsorbent (Hydrated Silica) 1.0
Hydroxymethyl cellulose 1.9
Lubricant (Stearic acid) 2.0
Moisture 1.0
100.0*
Another powder (Powder #2) was prepared in the same way
except the adsorbent and lubricant were not added to the
spray drier, but were mixed in manually to the unlubricated,
spray-dried powder so that the final composition of Powder
#2 was essentially the same as Powder #1.*
Powder #1 and Powder #2 were then tested to see
whether they were susceptible to demixing. Powder #2 was
first mixed for about 20 minutes in a blender without
heating. Then two 11-inch tubes 1'~ inches in diameter were
filled with Powder #1 and Powder #2, and were sealed at both
ends. These were then placed upright in a vibrating tray
and vibrated for 4 hours. The cylinders were then divided
into three equal portions - top, middle, and bottom. The
top and bottom portions were then analyzed by gas
chromotography using a capillary column, according to
AR-14036, to determine the amount of stearic acid in each
portion.
* A small amount of lubricant (0.2%) and adsorbent (0.1%)
were discharged into the spray drier during the spray
drying process.
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The percentage of stearic acid in the portions
containing Powder #1 was l.S1 percent (top) and 1.57 percent
(bottom). On the other hand the percentage of stearic acid
in the portions containing Powder ~2 was 1.52 percent (top)
and 2.24 percent (bottom).
These results indicate Powder #2 experienced
demixing because there is a difference of 0.72 percent
between the amount of stearic acid in the two portions.
This difference can lead to less uniformity in lubrication
and can cause problems in tableting such as capping due to
over lubrication, and die wall binding in the tablet press
due to under lubrication. Note that the difference between
the amount of stearic acid in the top and bottom portions of
Powder #1, which was prepared in accordance with the subject
matter, was only 0.06 percent.
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