U.S. patent number 3,639,169 [Application Number 04/820,287] was granted by the patent office on 1972-02-01 for direct compression vehicles and method therefor.
This patent grant is currently assigned to SuCrest Corporation. Invention is credited to Charles B. Broeg, Anthony Monti, John P. Troy.
United States Patent |
3,639,169 |
Broeg , et al. |
February 1, 1972 |
DIRECT COMPRESSION VEHICLES AND METHOD THEREFOR
Abstract
A granular, multicomponent direct compression vehicle is made by
uniformly blending at least one compactible material with other
materials, compacting the blend to a sheet, breaking the sheet up
into particles of a desired size and, if necessary, screening. The
resulting product when blended with an active material and, to the
extent necessary, a lubricant, can be directly formed into a
tablet.
Inventors: |
Broeg; Charles B. (Short Hills,
NJ), Monti; Anthony (Irvington, NY), Troy; John P.
(Hicksville, NY) |
Assignee: |
SuCrest Corporation (New York,
NY)
|
Family
ID: |
25230391 |
Appl.
No.: |
04/820,287 |
Filed: |
April 29, 1969 |
Current U.S.
Class: |
127/29; 8/526;
127/63; 264/122; 424/606; 424/686; 424/687; 424/690; 424/695;
424/720; 424/722; 424/723; 426/540; 426/548; 426/650; 426/656;
426/660; 514/777 |
Current CPC
Class: |
A61K
9/2095 (20130101); B01J 2/22 (20130101) |
Current International
Class: |
A61K
9/20 (20060101); B01J 2/22 (20060101); C13f
003/00 () |
Field of
Search: |
;127/29,30,63,59
;99/134R,DIG.4 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
A Lachmann, Food Engineering, 140, 143, 145, May 1966..
|
Primary Examiner: Wolk; Morris O.
Assistant Examiner: Marantz; Sidney
Claims
What is claimed is:
1. A method for producing a direct compression vehicle for tablets
comprising forming a dry mixture of a plurality of tablet
components, at least one of which is a compaction aid selected from
the group consisting of a polyethylene glycol having a molecular
weight in the range of from about 2,000 to about 10,000, glycerol
monostearate, sorbitol, lactose, mannitol, microcrystalline
cellulose, fatty acids, instantized gums, proteins, starch,
hydrolyzed polysaccharide derivatives, a free-flowing particulate
generally spherical, firm, agglomerate of sugar particles in a
matrix of noncrystalline sugar, or a free-flowing particulate
composition comprising an inert, edible diluent dispersed in a
matrix of a hydrophilic, hydratable, high polymer, said mixture
being free of active material, compacting said mixture to form a
compact, nonfriable sheet, and breaking up said sheet to form
particles thereof.
2. The granular product of the method of claim 1.
3. A method according to claim 1 wherein at least about 75 percent
of said mixture is formed into said sheet, and less than about 40
percent of said sheet is converted to dust upon said breaking
up.
4. A method according to claim 3 wherein said compaction aid
comprises from about 70 to about 95 percent of said mixture.
5. The method according to claim 1, including the steps of blending
the product thereof with an active material and directly
compressing the resulting blend to form a tablet.
6. The tablet of the method of claim 5.
7. A method according to claim 1 wherein said compaction aid is
selected from the group consisting of said generally spherical
sugar agglomerate and said particulate composition comprising an
inert, edible diluent dispersed in a matrix of a hydrophilic,
hydratable polymer.
8. A method according to claim 7 wherein said compaction aid is a
mixture of said agglomerate and said particulate composition.
9. A method according to claim 8 wherein the weight ratio of
agglomerate to particulate composition is in the range of from
about 50:1 to about 1:1.
10. The granular product of the method of claim 9.
11. A tablet obtained by blending the product of claim 10 with an
active material and directly compressing the resulting blend to
form a tablet.
Description
This invention relates to a multicomponent direct compression
vehicle and to a method for its manufacture. More particularly,
this invention relates to a particulate material, each granule of
which comprises an intimate mixture of two or more substances and
has substantially the same composition as the average composition
of the bulk of the material, which particulate material is useful
as a direct compression vehicle for the manufacture of tablets and
the like, and to a method for the manufacture of such particulate
material. This invention is particularly related to multicomponent
direct compression vehicles having a sugar as the predominant
component.
There are two general methods for forming tablets, i.e.,
compression of a dry particulate material and trituration, or
molding of a moist material, of which the first technique is by far
the most frequently employed. The compression technique may be
further subdivided into three major categories, viz, direct
compression, wet granulation and dry granulation. The direct
compression technique is the most desirable, in that it employs the
fewest steps and, in the case of the production of tablets
containing sensitive or unstable actives, such as certain
pharmaceuticals, minimizes the exposure to water or other
conditions tending to adversely affect stability of the active.
Unfortunately, however, it has been found that the direct
compression technique is of limited applicability.
First, most active materials possess poor compression properties,
and thus are unsuitable for this technique. In addition, many
actives are required in such small amounts per unit dosage form
that direct compression of the active alone is impractical, if not
impossible. As a result, the active must be admixed with a direct
compression vehicle, i.e., an inert composition which is compatible
with the active and has good compressibility. In addition, the
direct compression vehicle must have good flowability, good
stability under normal ambient conditions, no adverse effect on
tablet disintegration time, the ability to produce good tablet
surfaces, and low cost.
To date, however, no material has been found which satisfies all of
these criteria. For example, of the most popular of such
compression aids, spray-dried lactose possesses poor stability and
discolors on storing, dicalcium phosphate forms a tablet having
poor strength, and microcrystalline cellulose is expensive.
In addition to active and compression vehicle, a tabletting
formulation normally includes additives such as diluents,
lubricants, flavors, colors, disintegration agents and the like.
When the tabletting formulation includes a large number of
components, direct compression techniques are even less useful
because of the difficulty of assuring uniform mixing of the various
components on dry blending. As a result, a pregranulation
technique, normally wet granulation, has been found essential.
It is an object of the present invention to provide a new direct
compression vehicle and a process for its production.
It is a further object of this invention to provide a
multicomponent compression vehicle which may be combined with an
active and, if desired, a lubricant, and the resulting dry mixture
subjected to direct compression, and to a method for the production
of such vehicle.
Other objects and advantages of this invention will be apparent to
those skilled in the art in tablet manufacture upon review of the
specification and claims.
In general the present invention relates to a method comprising
mixing two or more components, compacting the resulting mixture to
form a sheet, breaking up the sheet into particles of a desired
size and, if desired, screening, and the product of such
process.
At least one of the components charged to the process of this
invention must be a compactible material. That is, at least one
material must be capable of forming a coherent film which resists
disintegration on handling. The material should be sufficiently
compactible and employed in amounts such that at least about 75
percent, and preferably at least about 85 percent, of the mixture
is converted to a compacted sheet, and less than about 40 weight
percent of the compacted mixture, and preferably less than about 20
weight percent, of the compacted mixture forms dust on granulation.
By the term "dust" is meant particles having their largest
cross-sectional dimension below about 325 mesh.
Suitable compactible materials, hereinafter referred to as
"compaction aids," are those which, after admixture with other
components, permit compaction to a homogenous, grindable product
which, after grinding to form a particulate product, is
compressible. Illustrative compacting aids include high molecular
weight ethyleneoxide polymers, i.e., polyethylene glycols having
molecular weights in the range of from about 2,000 to about 10,000
such as the "Carbowaxes," especially Carbowax 6,000; glycerol
monostearate; sorbitol; lactose; mannitol; microcrystalline
cellulose such as "Avicel"; fatty acids such as palmitic;
instantized gums such as those disclosed in U.S. Pat. Nos.
2,963,373 and 3,042,668; proteins; starch and hydrolyzed
polysaccharide derivatives such as hydrolyzed cereal starch and
dextrin; and certain sugar agglomerates.
One suitable sugar agglomerate is one comprising generally
spherical, firm porous agglomerates of sugar particles in a
cementum or matrix of a noncrystalline sugar. These agglomerates
are dry (from about 0.1 about 3 percent moisture), free-flowing
particles having particle sizes within the range of from about 325
to about 12 mesh, and are obtained by:
1. Spraying a particulate solid sugar with an aqueous solution of
binder;
2. Providing the resulting mixture with sufficient high-intensity
agitation to uniformly intermingle the sugar and binder and to
build up agglomerates of a desired size:
3. "Snowballing" the agglomerates to impart a general spherical
shape thereto and to firm or densify the agglomerate;
4. Drying; and, if necessary
5. Separating over- and under-sized agglomerates.
The particulate sugar can be a mono-, di- or tri- saccharide, such
as arabinose, xylose, ribose, fructose, mannose, galactose,
glucose, sucrose, maltose, lactose and the like, including mixtures
of two or more of such sugars, with sucrose being preferred. The
particulate sugar can be obtained synthetically or it can be a
refined natural product such as corn syrup solids, molasses solids,
honey solids, maple syrup solids and the like. The particle size of
the sugar is not narrowly critical, so long as it is small enough
to permit formation of agglomerates of the desired size. For most
purposes, ordinary 6X powdered sugar, of which most (95-99 percent)
passes through a 200-mesh screen, is suitable, If the agglomerate
is to be employed in the production of a chewable tablet, however,
the particulate solid sugar should be more finely divided to avoid
grittiness. For this use, the sugar should have substantially no
particles, i.e., not more than about 1percent, having sizes greater
than about 40 microns, and at least 50percent of the particles
should have sizes below about 25 microns. Preferred are sugars
having an average particle size of about 15 microns.
The second component which is employed to form the agglomerate is
an aqueous solution or dispersion of a polyhydroxy compound as a
binder. Illustrative polyhydroxy compounds include propylene
glycol, glycerol, erythritol, arabitol, xylitol, adonitol,
mannitol, dulcitol, sorbitol, sugars, such as arabinose, xylose,
ribose, glucose, mannose, levulose, fructose, sucrose, maltose and
lactose, dextrin and the like, with polyols of the formula
HOCH.sub.2 (CHOH).sub.x CH.sub.2 OH, wherein x is 1 to 4, and
sugars being preferred. The aqueous binder composition can be a
solution or dispersion of a pure compound, or can comprise two or
more polyhydroxy binders. The aqueous medium can be obtained
synthetically, or it can be a refined natural product, such as corn
syrup, molasses, honey, maple syrup and the like. Invert syrup is
preferred.
The concentration of binder in the aqueous medium is not narrowly
critical, provided that it is not so high as to cause
crystallization or provide solutions so viscous as to prevent
spraying and intimate intermingling and uniform distribution of
binder and solids. Thus, the concentration will depend upon the
solubility of the binder. For example, glucose ordinarily cannot be
employed in amounts greater than about 48 percent, whereas
propylene glycol, glycerol, mannitol and sorbitol can be present in
amounts up to about 80 percent. When invert sugar is the binder,
concentrations of from about 50 to about 80 percent are employed,
with concentrations of from about 70 to about 74 percent being
preferred. Other than this, the amount of water in the aqueous
medium should be so correlated with the desired ratio of binder to
sugar that agglomeration occurs. Thus the amount of water should be
insufficient to form a paste, and yet sufficient to minimize the
presence of powder, or unagglomerated sugar. In general it has been
found that the mixture of sugar and aqueous binder should contain
from about 2 to about 6 percent water, with amounts of about 4
percent water being preferred.
The initial contact of the solids and liquid is effected by
spraying the aqueous medium onto the dry solids at a rate such that
there is employed from about 0.1 to about 30 parts of binding agent
per 100 parts of solid.
The mixing is ordinarily conducted at about room temperature
(65.degree.-75.degree. F.). Higher and lower temperatures can be
employed, if desired, provided the properties of the aqueous medium
and the agglomerate product are not adversely affected. In
particular, the temperature of the aqueous medium may be varied to
achieve a desired viscosity for spraying. However, if the
temperature is too low, e.g., below about 50.degree. F., the
aqueous medium is ordinarily too viscous to be easily sprayed; and
if the temperature is too high, e.g., above about 200.degree. F.,
water may evaporate too rapidly to permit adequate control of the
characteristics of the binding solution. In addition, the use of
elevated temperatures during processing tends to result in a
discolored product, and also may cause dissolution of the dry
ingredient and thus adversely affect particle size and quality.
Simultaneously with the spraying, the mixture is agitated to effect
thorough and uniform intermingling of the sugar and binder and to
effect agglomeration. High-intensity mixing, such as is obtained
with a Patterson-Kelley Blender or a Lodige mixer is essential to
achieve the necessary thorough, uniform mixing and
agglomeration.
The agitation is continued until agglomerates of the desired size
are formed. Ordinarily, agglomeration is continued until
agglomerates above about 325 mesh are formed, and is terminated
before significant amounts of agglomerates larger than about 12
mesh are formed. The size of the agglomerate is also affected by
the ratio of aqueous binder to particulate sugar, with larger
agglomerates being formed when a greater proportion of liquid
medium is present.
The agglomerates typically have a narrow size distribution. That
is, high yields, normally 80 percent or more, of the agglomerates
fall within a few screen sizes. For example, when operating to
produce a 20- to 80-mesh agglomerate, at least 80 percent, and in
some instances at least 90 percent, of the agglomerated product
will fall within this range.
Simultaneously with and/or subsequent to agglomeration, the
agglomerates are "snowballed," i.e., subjected to a tumbling or
rolling operation, to impart a general spherical shape thereto. In
addition, the agglomerates are firmed or densified whereby the bulk
density is increased to about 50 to 100 percent over that of the
dry particulate sugar, and normally in the range of from about 30
to about 50 pounds per cubic foot.
Finally, and when necessary, the agglomerates are dried to a
moisture content of less than about 3 percent, and preferably less
than about 1.5 percent. Although complete drying is theoretically
possible, the moisture content of the product is ordinarily at
least about 0.1 to 0.2 percent. The temperature at which drying
occurs is not narrowly critical in all cases, but ordinarily the
temperature of the agglomerate should not exceed about 140.degree.
F. To achieve such drying, the product is preferably contacted with
hot air at a temperature not exceeding 190.degree. F. A preferred
drying technique is the use of a fluid bed dryer. In this manner,
very fine particles, i.e., dust, are separated from the
product.
If desired, the dried product may be screened to remove oversized
and undersized particles. Oversized particles are discarded or can
be reduced to smaller size. Undersized particles may be
recycled.
A second class of compacting aids comprises a product comprising a
dry (moisture content of less than about 4 percent), free-flowing,
particulate composition comprising an inert edible diluent
dispersed in a matrix of a hydrophilic, hydratable, high polymer,
such as the products of U.S. Pat. Nos. 2,963,373 and 3,042,668.
The diluent can be any normally solid material, i.e., any material
which is solid under conditions of normal atmospheric pressures and
temperatures, provided it is inert, edible and permissible in the
tablet formed from the direct compression vehicle. Thus it can be
either soluble or insoluble in water. If insoluble, however, it
must be capable of reduction to a size which is useful in the
practice of this invention, i.e., a size below about 200 mesh and
preferably below about 10 microns.
Preferred diluents include normally saccharine materials, i.e., a
mono- or disaccharide such as glucose, mannose, galactose,
fructose, arabinose, xylose, sucrose, maltose, and lactose; as well
as certain polyols of the formula HOCH.sub.2 (CHOH).sub.x CH.sub.2
OH, wherein x is 1 to 4, such as glycerol, erythritol, arabitol,
xylitol, adonitol, mannitol, dulcitol and sorbitol. In addition,
certain salts may be employed, including sodium chloride, sodium
citrate, calcium carbonate, calcium sulphate and tricalcium
phosphate. The diluent may be one or a mixture of two or more of
the aforesaid substances. In the event the diluent is a sugar, it
may be of synthetic or natural origin, and may be supplied to the
mixing step in the form of a solution or syrup, such as molasses,
affination syrup, invert syrup and the like.
The hydratable polymer includes hydrophilic polysaccharides,
hydrocolloids or proteinaceous materials which, although not
soluble in water, are hydrated upon admixture with water, and when
substantially fully hydrated form a clear aqueous sol of swollen
polymer and water. Illustrative examples of these high polymers
include starch, agar, locust bean gum, carrageen, dextrin, cereal
flour and the like.
The polymer, diluent and water are admixed in any convenient manner
and in proportions such that there is obtained a substantially
clear fluid mixture comprising an aqueous solution or dispersion of
diluent dispersed throughout the swollen hydrated polymer. The
precise conditions and proportions will vary widely, depending upon
the polymer employed, and the amount of and the additive employed.
The amount of water necessary to hydrate the hydrophilic polymer is
either known or is readily determined by the simple experiment of
adding water is known amount to a known amount of dry polymer until
a clear sol is obtained. In general, at least about 8 parts of
water are required per part of starch or dextrin, at least about 25
parts of water are required per part of locust bean gum, and at
least about 33 parts of water are required per part of agar or
carrageen. The foregoing amounts of water yields a product of
optimum properties, but lesser amounts of water, for example as low
as 50 percent or more of the above values, can be employed.
When the diluent is insoluble in water, no additional water is
required. When, however, the diluent is water-soluble, enough
additional water must be employed to dissolve the additive, For
example, if sucrose is added to a clear, fully hydrated starch the
resulting mixture becomes more fluid because the sucrose has a
greater affinity for water than starch, and thus removes some of
the water of hydration. If, however, in addition, there is added at
least 0.5 part of water per part sucrose to ensure solution of the
sucrose, the starch remains fully hydrated and the sucrose remains
in solution. Although greater quantities of water can be employed,
if desired, they are unnecessary and in fact disadvantageous in
increasing the heat load for drying and may preclude the use of
certain drying techniques, such as drum drying, which require a
relatively viscous liquid.
The ratio of water-soluble additive to hydratable polymer can vary
widely, depending upon the particular materials employed and the
characteristics desired in the product direct compression vehicle.
In general, however, ratios of from about 0.25 to about 250 parts
of additive per part of polymer, preferably from about 2 to about
50 parts additive per part of polymer, are useful. Ratios of from
about 20 to about 30 parts additive per part of polymer are most
preferred.
Drying of the resulting dispersion may be effected by a variety of
techniques, such as spray drying, belt drying, tray drying, drum
drying and the like. In a preferred technique, the dispersion is
dried by deposition on a heated surface to effect evaporation and
convert the dispersion into a dry, hot, plastic film, removing the
firm from the heated surface and attenuating the film while
simultaneously cooling it, to convert the plastic film to a brittle
or frangible condition. After the film has been thus cooled, it is
fragmented and ground to a desired particle size and the ground
product is employed.
A preferred way to practice the method of this invention is through
the use of a heated drum dryer and a cooled rotary takeoff reel
located a slight distance therefrom with a current of cooling air
passing therefrom.
In such a process the dispersion of the aqueous solution of a
saccharine material and the high polymer is prepared and introduced
into the nip between a pair of steam-heated oppositely rotating
drums at a rate to effect rapid evaporation of the water, but
without permitting the resultant dehydrated product which contains
not more than 4 percent moisture, and which forms a relatively
thick plastic film on the surfaces of the drums, to reach a
temperature at which destructive decomposition would begin. Thus
the temperature of the dehydrated material should not exceed about
350.degree. F., and the operating conditions of the drums should be
adjusted accordingly. At the line of transfer to the reel, which is
rotating with a peripheral speed greater than that of the drum, the
hot dehydrated film is removed by a doctor blade from its
associated drum and transferred to the reel across a current of
cooling air, having a 60.degree.-80.degree. F. temperature, which
effects an initial cooling of the dehydrated material to near room
temperature of about 70.degree. F. to about 95.degree. F. and the
cooling air at the line of removal of the film from the reel aids
both its removal therefrom and a final cooling to a brittle or
frangible state. The frangible film then drops away from the reel
as a brittle sheet or fragments onto a conveyor for transport to a
storage bin or to a comminuting device for reduction to the desired
particle size for direct tabletting.
If only one takeoff reel is used, it will, of course, be necessary
to provide a scraper or other means on the opposite drum to prevent
passage of the hot dehydrated film therearound and force it over
onto the other drum.
Although in the foregoing description of the method mention has
been made of a two-drum dryer with either a single or two takeoff
reels, it will be appreciated that a single drum dryer with a
single takeoff reel can be used with equal effectiveness.
A particularly preferred product is obtained when a mixture of the
above-described spherical agglomerates and flakes is employed as
the compacting aid. Tablets made from the direct compression
vehicles of this invention employing the spherical agglomerate
alone tend to have poor color stability, and tablets made from the
vehicles of this invention employing the flake material have poor
strength characteristics when magnesium stearate is employed as a
lubricant during tabletting.
When both materials are employed, however, the tablets produced
from the resulting vehicle possess both good strength and color
stability. The weight ratio of spherical agglomerate to flake can
obviously vary widely depending upon the composition of these
materials as well as the composition and properties of the
remaining components and the compaction properties desired in the
directly compressible vehicle. In general, however, this ratio is
in the range of from about 50:1 to 1:1, preferably from 20:1 to
30:1, and most preferably about 25:1.
The remaining components which are charged to the mixing step of
the process of this invention are those commonly employed in
tablets, other than the active material. By the term "active
material" is meant any material intended for ingestion having a
beneficial or desirable effect on the user. Suitable active
materials include therapeutic materials, such as anesthetics,
antibiotics, antitussives, vitamins, aspirin, antacids, and the
like; foodstuffs such as cocoa, dried oats, fruit flakes, and the
like; edible dyes and other food additives; and so on. Illustrative
additional components include flavors, colors, diluents, materials
to impart the desired texture, hardness, lubricity and
disintegration rate in use of the ultimate tablet and the like. The
process of this invention is of particular importance when granular
sugar, especially sucrose, is employed as a diluent.
The proportions of the several components in the mixture to be
compacted is not critical, provided that the desired degree of
compaction is achieved, and the granular product has the desired
properties. In general, there should be at least 10 weight percent
of one or more compaction aids, with amounts in the range of about
70 to about 95 percent being most usual. In some instances, as
where glycerol monostearate is employed, the compaction aid may be
present in amounts as low as about 3 percent.
Particularly preferred direct compression vehicles within the scope
of the present invention are those wherein a sugar, especially
sucrose, is employed in admixture with one of the above-mentioned
compaction aids. In such compositions, the sugar comprises from
about 50 to about 90 percent of the direct compression vehicle.
Although not essential to the process of this invention, it is
desirable that the compacting aid and the remaining components have
substantially similar particle sizes to minimize segregation by
size on handling before compacting and compacted product. As a
general rule, the particle sizes of the components should not vary
more than .+-.50 percent from the mean particle size of the entire
mixture. It should be noted, however, that at small mean particle
sizes, deviations of larger than 50 percent may be tolerated
because at lower overall dimensions, small absolute variations in
particle size represent larger percentages of the mean size.
The various components are then mixed by suitable means, such as
ribbons blenders, Lodige mixers, Patterson-Kelley mixers and the
like to produce a uniform blend of the several particulate
components.
The resulting blend is fed to a compactor, such as a Compacting
Rolls made by Komarek-Greaves Co., or a Chilsonator made by
Fitzpatrick Co., which converts the particulate mixture into a
compact, nonfriable sheet. The degree of compaction will vary
widely, depending upon the nature and proportions of the compacting
aid and the remaining components, but it is essential that the
sheet does not disintegrate under slight pressure. More
particularly, the sheet should not, upon granulation, form more
than about 40, preferably about 20, percent dust upon
granulation.
The next step of the process of this invention is granulation,
i.e., reduction of the compacted sheet to particles of a desired
average size, preferably within the range of from about 16 to about
325. This size reduction is effected with conventional equipment,
such as Fitzmills and the like, and may be accomplished in one or
more steps.
The final, and optional, step of the process of this invention for
producing a directly compressible vehicle is screening of the
particulate product to a desired size range. Illustrative size
ranges include 16 to 100 mesh; 100 to 200 mesh; and 200 to 325
mesh. The particular mesh size will vary depending upon the
particular active with which the vehicle of this invention is to be
blended and formed into a tablet. In general, the size range should
approximate that of the active to ensure a uniform blend of vehicle
and active in the tabletting mixture and the tablet produced
therefrom.
The vehicle is a g free-flowing granular material and imparts
improved flow characteristics to the active material and other
components of the blend, thereby assuring ease of tabletting. The
uniform granular direct compression vehicle of this invention is
employed by blending with the active material and, if necessary, a
lubricant, and compressed in conventional manner to form a tablet
or wafer.
The following examples are illustrative. Unless otherwise
specified, all parts and percentages are by weight. In the
examples, the following products were employed:
Flake A-- a flake containing 34 percent starch, 27 percent sucrose
and 39percent invert (sucrose and invert dispersed throughout a
starch matrix) prepared by mixing 3,750 parts water, 350 parts
starch and 284 parts powdered sucrose, cooking the resulting
mixture at 180.degree. F. to hydrate the starch and dissolve the
sucrose, and adding 571 parts of a 70 percent invert syrup,
followed by drum drying to about 2 percent moisture and granulating
to about one-half inch.
Flake B-- a flake product containing about 25 percent invert and 50
percent sucrose dispersed in a matrix of 25 percent starch produced
in a manner similar to Flake A.
Flake C-- a flake product containing about 45 percent invert and 30
percent sucrose dispersed in a matrix of 25 percent starch produced
in a manner similar to Flake A.
Flake D-- a flake product containing about 25 percent starch and 75
percent sucrose produced in a manner similar to Flake A.
Agglomerate A-- a product comprising generally spherical
agglomerates of about 8.5 percent invert, 91.5 percent sucrose and
less than 1 percent water prepared by spraying a 72.degree. Brix
full invert syrup on sucrose in a Patterson-Kelley blender, drying
and screening to a fraction having a size of from 20 to 80
mesh.
Agglomerate B-- a product comprising generally spherical, uniform
agglomerates containing about 2.5 percent invert, 97.5 percent
sucrose and less than about 1 percent moisture produced in a manner
similar to Agglomerate A, except that the syrup comprised 20
percent invert and 52 percent sucrose.
Unless otherwise specified, all parts and percentages are by
weight.
EXAMPLE 1
A dry blend of 50 parts of Flake C and 50 parts of powdered sugar
was fed to a Chilsonator operated at a roll speed of 15 r.p.m. and
hydraulic pressure of 200 p.s.i. The resulting compacted sheet was
fed to a Fitzmill equipped with a 2A screen and number 225 K blades
operating at 2,200 r.p.m. The resulting particulate product was
screened to provide +30-mesh; 30 to 60-mesh; 60 to 80-mesh and
-80-mesh fractions as follows:
Particle Parts by Size, mesh Weight of Total +30 9.2 30-60 66.8
60-80 15.0 -80 6.4
The thus obtained product was employed to produce 13/32 -inch,
0.5-gram tablets at 3,000 and 9,000 p.s.i. and only slight capping
was observed.
EXAMPLE 2
Employing procedures similar to those described in example 1,
except that the initial blend comprised 10 parts of Flake B and 30
parts of sucrose, there was produced a compacted granular product
having the following particle size distribution:
Particle Parts by Size Weight of Total +30 mesh 3.8 30-60 mesh 75.4
60-80 mesh 12.0 -80 mesh 5.2
The thus obtained product could be used as a direct compression
vehicle.
EXAMPLE 3
A mixture of 1,125 parts of Agglomerate B, 37 parts of Flake A, 5
parts of magnesium stearate and 83 parts sugar was charged at a
rate of 3,000 parts per hour to a Chilsonator at a roll speed of 16
r.p.m. and a hydraulic pressure of 1,200 p.s.i., and the resulting
compacted sheet was fed to a Fitzmill equipped with 225 K blades
and a No. 1 screen operating at 1,590 r.p.m. The resulting granular
product contained 3.95 percent invert, 0.5 percent magnesium
stearate, 0.35 percent moisture, 0.7 percent starch and 94 percent
sucrose and had the following sieve analyses:
Particle Size Parts by Weight +20 mesh 0 20-40 mesh 2.8 40-100 mesh
14.8 100-200 mesh 21.0 -200 mesh 61.4
EXAMPLE 4
A mixture of 250 parts of the -200 mesh fraction of example 3, 930
parts of Agglomerate A, 30 parts of Flake A and 40 parts of sucrose
was blended, pulverized by a Mikro pulverizer to a particle size of
less than about 800 mesh (95 percent through 200 mesh), and fed to
a Chilsonator under essentially the conditions described in example
3. The product, after granulation on the Fitzmill, was screened
through 40-, 100- and 200-mesh screens to yield three products
(coarse-- plus 40 mesh; medium-- 40 to 100 mesh; fine-- 100 to 200
mesh). The yields and analyses of these products, based upon the
dry blend fed to the Chilsonator, is as follows:
Product Coarse Medium Fine Yield, % 21.6 16.8 26.4 Density, g./cc.
0.796 0.811 0.756 Sieve Analyses 30 20 mesh 0.8% Tr Tr 20-40 mesh
93.3% 0.2% Tr 40-60 mesh Tr 60.5% Tr 60-80 mesh Tr 22.3% 8.8%
80-100 mesh Tr 8.0% 41.3% 100-140 mesh Tr 5.2 25.6 140-200 mesh Tr
1.0 20.3 31 200 mesh Tr Tr
EXAMPLE 5
Employing procedures and equipment similar to these described in
example 4, a blend of 25 parts of a particulate composition
containing 90 percent tricalcium phosphate and 10 percent locust
bean gum made as described in U.S. Pat. No. 3,420,668 and 75 parts
sugar was fed to the Chilsonator at a roll pressure of 1,400 p.s.i.
The +200 mesh portion of the granulated product comprised 0.4
percent of a +40-mesh fraction; 1.9 percent of a 40- to 100-mesh
fraction and 97.7 percent of a 100- to 200-mesh fraction.
EXAMPLE 6
Employing procedures and equipment similar to those described in
example 4, a blend of 25 parts microcrystalline cellulose and 75
parts sucrose was pulverized and fed to the Chilsonator at a roll
pressure of 1,200 p.s.i. The +200-mesh product comprised 0.3
percent +40-mesh fraction, 15.5 percent 40-100-mesh fraction and
84.5 percent 100-200-mesh fraction.
EXAMPLE 7
Employing procedures and equipment similar to those described in
example 4, a blend of 10 parts of Carbowax 6,000 and 90 parts
sucrose was pulverized and fed to the Chilsonator at a roll
pressure of 1,200 p.s.i. The +200-mesh product comprised 3.9
percent +40-mesh fraction; 45.6 percent 40-100-mesh fraction and
50.5 percent 100-200-mesh fraction.
EXAMPLE 8
Employing procedures and equipment similar to those of example 4, a
dry blend of 30 parts sorbitol and 70 parts sugar was pulverized
and fed to the Chilsonator at a roll pressure of 1,200 p.s.i. to
yield a +200-mesh product comprising 2.1 percent +40-mesh fraction,
76.4 percent of a 40-100-mesh fraction and 21.5 percent of a
100-200-mesh fraction.
EXAMPLE 9
Employing procedures and equipment similar to those of example 4, a
dry blend of 75 parts dextrose and 25 parts sorbitol was fed to the
Chilsonator to yield a +200-mesh product comprising 10.4 percent of
a +40-mesh fraction, 66.3 percent of a 40-100-mesh fraction and
22.2 percent of a 100-200-mesh fraction.
EXAMPLE 10
Employing procedures and apparatus similar to those of example 4, a
blend of 1 part of Flake D and 2 parts sucrose was fed to the
Chilsonator at a roll pressure of 1,100 p.s.i. to yield a +200-mesh
product comprising 3.6 percent of a +40-mesh fraction, 60 percent
of a 40-100-mesh fraction and 36.4 percent of a 100-200-mesh
fraction.
EXAMPLE 11
Employing procedures and apparatus similar to those of example 4, a
blend of 50 parts corn starch, and 50 parts sucrose were fed to the
Chilsonator to yield a +200-mesh product comprising 8.4 percent of
a +40-mesh fraction, 68 percent of a 40-100-mesh fraction and 22.6
percent of a 100-200-mesh fraction.
EXAMPLE 12
Employing procedures and apparatus similar to those of example 4, a
blend of 15 parts of a flake comprising 5 percent agar, 31/2
percent starch and 911/2 percent sucrose made as described in U.S.
Pat. No. 2,963,373 and 85 parts sucrose was fed to the Chilsonator
at 1,200 p.s.i. roll pressure to yield a +200-mesh fraction
comprising 9.2 percent of a +40-mesh fraction, 72 percent of a
40-100-mesh fraction, and 18.8 percent of a 100-200-mesh
fraction.
EXAMPLE 13
Employing procedures and apparatus similar to those of example 4, a
blend of 10 parts of a flake product produced by drum drying a
mixture of 833 parts of water, 9 parts agar, 9 parts locust bean
gum, 12 parts tapioca flour (starch) and 200 parts sucrose, and 20
parts sucrose were fed to the Chilsonator at 1,200 p.s.i. roll
pressure to yield a +200 -mesh product comprising 4.6 percent of a
+40-mesh product, 78.4 percent of a 40-100 -mesh product and 17
percent of a 100-200-mesh product.
Each of the direct compression vehicles of the foregoing examples
can be blended in accordance with the following recipes and
compressed to form tablets and wafers.
A. CONFECTIONERY TABLETS OR WAFERS 1. LEMON FLAVORED confectionery
tablet: 100.0 pts. direct compression vehicle 1.0 pt. citric acid,
dry 0.25 pt. encapsulated lemon flavor 0.10 pt. yellow color No. 5
1.0 pt. magnesium stearate 2. GRAPE FLAVORED tablet: 50.0 pts.
direct compression vehicle 50.0 pts. 6X powdered sugar 2.0 pts.
tartaric acid 0.25 pt. grape flavor 0.05 pt. grape color 0.5 pt.
calcium stearate 3. CHERRY FLAVORED confectionery tablet: 100.0
pts. direct compression vehicle 2.0 pts. fumaric acid 0.2 pt.
cherry flavor 0.1 pt. red color 1.0 pt. magnesium stearate
B. PHARMACEUTICAL FORMULATIONS 1. 50.0 pts. direct compression
vehicle 37.5 pts. aluminum hydroxide 1.0 pt. magnesium stearate 2.
100.0 pts. direct compression vehicle 25.0 pts. calcium carbonate
5.0 pts. magnesium carbonate 1 drop peppermint oil 2.0 pts.
magnesium stearate 3. 100.0 pts. direct compression vehicle 25.0
pts. acetyl salicylic acid 15.0 pts. corn starch 2.0 pts. magnesium
stearate 90.0 pts. direct compression vehicle 10.0 pts. vitamin C
in dry form 2.0 pts. magnesium stearate
Other active ingredients of use in blends with the agglomerate are:
sodium bicarbonate, acetanilid, phenacetin, and magnesium
trisilicate.
C. SPECIALTY PRODUCTS 1. INVERTASE SUGAR TABLET 96.4 pts. direct
compression vehicle 3.6 pts. liquid triple strength invertase
(K=0.9) 1.0 pt. magnesium stearate 2. COCOA-SUGAR TABLET 90.0 pts.
direct compression vehicle 10.0 pts. high fat cocoa 0.2 pts.
dendritic salt 1.0 pt. magnesium stearate After blending, the
mixture is tabletted to form a cocoa-sugar tablet. 3.
SUGAR-SYNTHETIC SWEETENER TABLET 450.0 pts. direct compression
vehicle 7.16 pts. calcium cyclamate 0.8 pt. sodium saccharin 5.0
pts. calcium stearate 4. HIGHLY CONCENTRATED COLOR TABLET 90.0 pts.
direct compression vehicle 10.0 pts. dried yellow FD & C No. 6
10.0 pts. sodium benzoate 5. YEAST FOOD TABLET 34.0 pts. calcium
sulfate (2H.sub.2 0) 23.0 pts. flour 9.0 pts. ammonium chloride
0.25 pt. potassium bromate 17.75 pts. sodium dihydrogen phosphate
16.0 pts. salt 900.0 pts. direct compression vehicle 10.0 pts.
magnesium stearate
* * * * *