March 17, 1964
1.. N. ELOWE ETAL
3,125,491
CHEWABLE usum'rmc vmum TABLET
Filed April 6, 1962
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INVENTORS.
L can; Nam/r E/ouc
Gerald James Jae/(s00 Jr:
BY / , ,
,
AG -
United States Patent 0 Mlc€
3,125,491
' ‘Patented Mar. 17, 1964
pression-coated” as is described in Remmington, Practice
of Pharmacy, 11th edition, page 406 (1956). Essentially
this step involves actually compressing a coating on a
3,125,491
CHEWABLE TEMATENTC VlTAMlN TABLET
Louis Nash- Elowe and Gerald James Jackson, Jr., Bar
d‘onia, N.Y., assignors to American Cyanamid Cor parry, Stamford, (1021111., a corporation of Maine
core, usually with a tablet press.
If the core is pan
coated, for instance, the sugar coating is subject to crack
ing when the iron granulation is compressed superim
Filed Apr. 6, 1952, Ser. No. 135,664
1 Claim. (Cl. 167-452)
posed thereon. The sugar must be “compression-coated”
onto the ascorbic acid core in order to produce the two
layered tablet of this invention.
This invention relates to novel medicinal chewable
Compression should be carried out preferably under
tablets. More particularly, this invention relates to a 10
low humidity conditions and with thoroughly dried gran
ulations because of the adverse effect of moisture on the
layered tablet, one of these layers consisting of a sugar
ascorbic acid.
compression-coated core containing a form of vitamin
The arrangement of the active ingredients in the two
C, the other layer consisting of a granulation of thera
peutic ferrous iron. The chewable tablet of this inven 15 layered tablets of this invention is critical. For instance,
if the iron is compressed into the sugar compression
tion is especially useful for combining incompatible‘
coated core, and the ascorbic acid compression-layered
' medicaments such as ascorbic acid and iron, in a pleasant
tablet superimposed on a second tablet to form a two
tasting single dosage unit.
Therapeutic compositions containing iron for oral and
on one face of this core, stability would still be a prob
lem. The ascorbic acid, although separated from the iron
would be exposed to attack by the oxygen and moisture
of the atmosphere. It is evident that this arrangement of
active ingredients would not be acceptable.
parenteral use are usually administered in concentrated
form to people su?iering from iron de?ciency anemia.
The oral administration of therapeutic ferrous iron as
A pleasant tasting wetting agent, in the spirit of this
the sulfate, fumarate, saccharide, gluconate, lactate, etc.,
invention, can be incorporated in the:
and a form of vitamin C such as ascorbic acid, for use
in treating iron de?ciency anemias, is well-known. Of the 25
various forms of ferrous iron, ferrous fumarate is well
tolerated and generally preferred.
(3) Sugar granulation around the ascorbic acid. '
Generally, chewable hematinic tablets are preferred
when people are reluctant to take tablets or capsules be
cause of swallowing di?‘iculties. Children are particu
larly a problem in this regard. It would also be an ad
vantage to make available to people who take hematin
30
polyoxyethylene-polyoxypropylene condensation product,
manufactured by the Wyandotte Chemical Corp, Wyan
dotte, Michigan, because of its taste. The added wetting
agent, of course, helps to reduce the incidence of fecal
impaction associated with the administration of iron
amounts.
The actual preparation of an oral dosage form, such
as a chewable tablet containing these therapeutic agents,
orally.
An oral therapeutic dose of ferrous iron is about 10—50
mg. and ascorbic acid is usually dispensed in 2S—100 mg.
doses, depending upon the individual and the degree of
however, prevents certain difficulties, because of the oxi
dizing effects of iron on ascorbic acid, and the lability
of ascorbic acid to oxygen and moisture, especially at
illness. An average dose is about 20 mg. of iron and
50 mg. of ascorbic acid.
Other vitamins and minerals can be incorporated, de
higher temperatures. Furthermore, when ascorbic acid
decomposes, a gas evolves which could be hazardous in
an air-tight package.
In the past, hematinic tablets have been prepared with
pendent upon the individual requirements. These medi
caments can be added to the granulations by known
granulations of ascorbic acid and iron compressed into
a single tablet separated by an inert middle layer. How
methods for incorporation into the two-layered tablets
of this invention.
ever, when these tablets are randomly ?lled into a pack
age, the iron layer of one tablet is in contact with the
Various pharmaceutically acceptable dyes may be used
in the tablet of this invention to produce two-color and
ascorbic layer of another tablet, consequently oxidation
two-tone tablets.
of the ascorbic acid may occur during storage. This oxi
dation can be prevented by coating these tablets with
vsugars, fats, waxes, polyethylene glycol or other known
coatings. However, this extra step would add to the
manufacturing cost, and in the case of the sugar coating,
would add to the unwanted bulk of the tablet.
The two-layered tablet of this invention possesses great
er chemical stability of the ascorbic acid; has favorable
size characteristics, lending itself to ease of administra
tion; and is pleasant tasting and elegant.
The tablets of this invention are also illustrated in the
pared as follows: I
attached drawing.
(1) Prepare a core containing a therapeutic dose of
ascorbic acid.
(2) Compression-coat this core with an inert sugar
granulation to form one layer.
(3) Prepare a granulation of a therapeutically ac
FIGURE 1—Exploded outer side-view of the two
layered tablet. One of the layers contains the mannitol
coated ascorbic acid core (1).
The sugar coating on the ascorbic acid must be “com
The second layer con
tains the ferrous fumarate granulation compressed there
on (2).
(4) Compress the iron granulation on one face of the 65
peutically acceptable ferrous iron compound.
Pharmaceutically acceptable ?avors
may also be added to granulations in the tablet of this
invention to mask the taste of iron and ascorbic acid, and
render it a more elegant chewable tablet.
According to the present invention, a stable, pleasant
tasting, two-layered chewable hematinic tablet is pre
sugar-coated ascorbic acid layer of step 2.
Thus, a two layered tablet is produced containing:
(1) A layer of sugar coated ascorbic acid.
(2) A superimposed layer containing a dose of thera
Any physiologically acceptable wetting agent can be
used, but we prefer to add Pluronic F-68 powder, a
ics rather regularly, a pleasant tasting chewable dosage
form containing both ascorbic acid and iron in therapeutic
ceptable ferrous iron compound.
(1) Core with ascorbic acid,
(2) Ferrous fumarate granulation,
FIGURE 2——Cr0ss-section of the side-view of the tablet
showing the ascorbic acid core clearly visible (3); the
mannitol coating about the ascorbic acid core (1). The
ferrous fumarate granulation (2) compressed thereon.
70 The two granulations are clearly separated from each
other by the mannitol coating.
The following'examples are illustrative of the processes
3,125,491
3
and products of this invention and are not to be con
strued as limiting.
EXAMPLE 1
lation was passed through a 12 mesh screen and thorough
ly dried at 110° Fahrenheit for 12 hours. It was then
passed through a 30 mesh screen. The lubricants were
added and blended thoroughly.
(A) Preparation of Tablet Cores
(D) Compression of Layered Tablet
Each core contains:
The two layered tablets were compressed as follows:
Ascorbic acid, U.S.P __________________ __mg__ 50.00
Mannitol, NF ________________________ __mg__ 75.20
Sodium cyclamate, N.F ________________ __mg__ 10.00
Acacia, powdered, U.S.P _______________ __mg__ 5.00
Ethyicellulose ________________________ __mg__
1.20
Dried raspberry ?avor _________________ __mg__
2.0
First Stage: Compression of asorbic acid core.
Second Stage: Compression of the mannitol coating
about the core.
Third Stage: Compression of the ferrous fumarate
layer to one face of the coated core.
Granulating Solution
EXAMPLE 2
Ethylcellulose _________________________ __mg__ 1.2
213 alcohol ____________________________ __ml__ 0.05
Using the procedure of Example 1, two-layered tablets,
wherein one layer consisted of a compression coated core
Red dye, PD. and C ___________________ __mg__ 0.10
of ‘ascorbic acid, were prepared containing 50 mg. of
Lubrication
polyoxyethylene-polyoxypropylene copolymer wetting
agent in the ferrous fumarate layer replacing 50 mg. of
Magnesium stearate, U.S.P ______________ __mg__ 2.25 20
the mannitol.
Talc, U.S.P ____________________________ __mg__ 2.25
The ascorbic acid was blended with mannitol, ?avor,
sodium cyclamate and acacia. The resulting powder mix
EXAMPLE 3
Using the procedure of Example 1, two-layered tablets,
wherein one layer consisted of a compression coated core
ture was passed through a 40 mesh screen and then gran—
of ascorbic acid, were prepared containing 25 mg. ascorbic
acid per tablet in place of the 50 mg. of Example 1.
ulated with the ethylcellulose-dye-alcohol solution and
?nally with 213 alcohol. The wet granulation was passed
through a 12 mesh screen and dried at 70° to 110°
EXAMPLE 4
Fahrenheit for 8 hours. The dried granulation was passed
through a 16 mesh screen.
Using the procedure of Example 1, two layered tablets,
The lubricants were added
and blended thoroughly.
wherein one layer consisted of a compression coated core
of ascorbic acid, were prepared containing sodium ascor
bate in amounts equivalent to ‘about 100 mg. ascorbic
(B) Preparation of Sugar Coating
Each Mannitol coating contains:
acid.
Mannitol, NF _______________________ "mg" 277.62
Methylcellulose, 400 cps, U.S.P ________ __mg__
6.00
Sodium cyclamate, NF _______________ __mg__
2.40
Dried lemon ?avor ___________________ __mg__
3.83
wherein one layer consisted of a compression coated core
Granulating Solution
rate in an amount equivalent to about 10 mg. of iron in
I
EXAMPLE 5
Using the procedure of Example 1, two layered tablets,
of [ascorbic acid, were prepared containing ferrous fuma
0.15
place of the 60.846 mg. of ferrous fumarate (equivalent
to 20 mg. of iron) in Example 1.
Magnesium stearate, U.S.P ______________ __mg__ 4.50
Using the procedure of Example 1, two layered tablets,
Talc, U.S.P ___________________________ __mg__ 4.50
wherein one layer consisted ‘of "a compression coated core
Puri?ed water _________________________ __rnl__ 0.055
Yellow dye, PD. and C. #5 ____________ __mg__
EXAMPLE 6
Lubrication
of ascorbic acid, were prepared containing ferrous sulfate
The mannitol, methylcellulose, sodium cyclamate and
in an amount equivalent to about 50 mg. of iron.
Having thus described our invention, we claim:
?avor were blended and passed through a 40 mesh screen,
then granulated with the dye-water solution and ?nally
A chewable hematinic vitamin tablet form comprising
with puri?ed water. The wet granulation was passed
through a 12 mesh screen and thoroughly dried at 110°
Fahrenheit for 12 hours. This dried granulation was
passed through a 20 mesh screen.
a pro-compressed vitamin tablet core portion containing
ethylcellulose-granulated mannitol and a source of vitamin
C, said tablet core portion having smaller dimensions than
the desired ?nished tablet, an inert compression-coated
methylcellulosegranulated mannitol barrier coating com
pletely surrounding said vitamin tablet core portion and
The lubricants were
added and blended thoroughly.
(C) Preparation of Ferrous Fumarate Layer
a hemantinic granulation layer containing methylcellulose
granulated mannitol and a therapeutically ‘acceptable fer
Each ferrous fumarate layer contains:
Ferrous fumarate ___________________ __mg.__ 160.846
Mannitol, N.F ______________________ __mg__ 205.704
Methylcellulose, 400 cps _____________ __mg__
6.000
rous iron compound, said chewable vitamin tablet form
having the hematinic tablet layer compressed to one face
Sodium cyclamate, N.F ______________ __mg__
Dried spearmint ?avor _______________ __mg_..
tion.
of the mannitol-coated precompressed vitamin core por
12.000
6.25
Granulating Solution
References Cited in the ?le of this patent
UNITED STATES PATENTS
Puri?ed water __________________________ __ml__ 0.06
Green dye, PD. and C. #2______________ __mg__
0.2
Lubrication
Magnesium stearate, U.S.P ______________ __mg__ 4.500
Talc, U.S.P __________________________ __mg__ 4.500
1 Equivalent to 20 mg. iron.
The ferrous fumarate, mannitol, methylcellulose, sodi
um cyclamate, and ?avor were blended and passed through
a 40‘ mesh screen, then granulated with the dye-water
solution and ?nally with puri?ed water. The wet granu
70
2,410,110
2,811,483
2,822,317
2,887,436
2,939,820
2,985,559
2,996,431
3,019,169
3,048,526
Taylor _______________ __ Oct. 29,
Alterno et val __________ __ Oct. 29,
Gulesich et al __________ __ Feb. 4,
Kloize et al ___________ __ May 19,
Gerber et al. __________ __ June 7,
Coles ________________ __ May 23,
Barry _______________ __ Aug. 15,
Klumpp et al ___________ __ Jan. 30,
Boswell ______________ __ Aug. 7,
(Qther references on foiiowiug page)
1946
1957
1958
1959
1960
1961
1961
1962
1962
3,125,481
1
‘ ‘-
s
FOREIGN PATENTS
807,638
1851,761
Great Britain _________ __ Jan. 21, v1959
Great Britain __________ __ Oct. 19, 1960
6
Press-Coated =and Multi-Layer Tablets,” 12 1113., copy
right 1959, Atlas Powder Co., Wilmington 99, Del-aware,
published August 1959.
American Cyanamid “Fen'o-Mandets,” registered Trade
OTHER REFERENCES
5 mark No. 735,221, registered July 31, 1962, ?rst used
“Atlas-Guide to Using Mannitol, N. F. as a Base in
in ‘commerce December 15, 1961.