US3125491A - Chew able hematinic vitamin tablet - Google Patents

Description

March 17, 1964 1.. N. ELOWE ETAL 3,125,491

CHEWABLE usum'rmc vmum TABLET Filed April 6, 1962 II [III/III,

I I l '0 III III! II a:

INVENTORS. L can; Nam/r E/ouc Gerald James Jae/(s00 Jr:

United States Patent M 3,125,491 CHEWABLE TEMATENTC VlTAMlN TABLET Louis Nash- Elowe and Gerald James Jackson, Jr., Bardonia, N.Y., assignors to American Cyanamid Cor parry, Stamford, (1021111., a corporation of Maine Filed Apr. 6, 1952, Ser. No. 135,664 1 Claim. (Cl. 167-452) This invention relates to novel medicinal chewable tablets. More particularly, this invention relates to a tablet superimposed on a second tablet to form a twolayered tablet, one of these layers consisting of a sugar compression-coated core containing a form of vitamin C, the other layer consisting of a granulation of therapeutic ferrous iron. The chewable tablet of this invention is especially useful for combining incompatible medicaments such as ascorbic acid and iron, in a pleasant tasting single dosage unit.

Therapeutic compositions containing iron for oral and parenteral use are usually administered in concentrated form to people sufiiering from iron deficiency anemia.

The oral administration of therapeutic ferrous iron as the sulfate, fumarate, saccharide, gluconate, lactate, etc., and a form of vitamin C such as ascorbic acid, for use in treating iron deficiency anemias, is well-known. Of the various forms of ferrous iron, ferrous fumarate is well tolerated and generally preferred.

Generally, chewable hematinic tablets are preferred when people are reluctant to take tablets or capsules because of swallowing difiiculties. Children are particularly a problem in this regard. It would also be an advantage to make available to people who take hematinics rather regularly, a pleasant tasting chewable dosage form containing both ascorbic acid and iron in therapeutic amounts.

The actual preparation of an oral dosage form, such as a chewable tablet containing these therapeutic agents, however, prevents certain difficulties, because of the oxidizing effects of iron on ascorbic acid, and the lability of ascorbic acid to oxygen and moisture, especially at 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 granulations of ascorbic acid and iron compressed into a single tablet separated by an inert middle layer. However, when these tablets are randomly filled into a package, the iron layer of one tablet is in contact with the ascorbic layer of another tablet, consequently oxidation of the ascorbic acid may occur during storage. This oxidation can be prevented by coating these tablets with sugars, 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.

According to the present invention, a stable, pleasant tasting, two-layered chewable hematinic tablet is prepared as follows: I

(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 acceptable ferrous iron compound.

(4) Compress the iron granulation on one face of the 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 therapeutically acceptable ferrous iron compound.

The sugar coating on the ascorbic acid must be com- 3,125,491 lc 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 core, usually with a tablet press. If the core is pancoated, for instance, the sugar coating is subject to cracking when the iron granulation is compressed superimposed thereon. The sugar must be compression-coated onto the ascorbic acid core in order to produce the two layered tablet of this invention.

Compression should be carried out preferably under low humidity conditions and with thoroughly dried granulations because of the adverse effect of moisture on the ascorbic acid.

The arrangement of the active ingredients in the twolayered tablets of this invention is critical. For instance, if the iron is compressed into the sugar compressioncoated core, and the ascorbic acid compression-layered on one face of this core, stability would still be a problem. 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.

A pleasant tasting wetting agent, in the spirit of this invention, can be incorporated in the:

(1) Core with ascorbic acid, (2) Ferrous fumarate granulation, (3) Sugar granulation around the ascorbic acid.

Any physiologically acceptable wetting agent can be used, but we prefer to add Pluronic F-68 powder, a polyoxyethylene-polyoxypropylene condensation product, manufactured by the Wyandotte Chemical Corp, Wyandotte, 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 orally.

An oral therapeutic dose of ferrous iron is about 1050 mg. and ascorbic acid is usually dispensed in 2S100 mg. doses, depending upon the individual and the degree of illness. An average dose is about 20 mg. of iron and 50 mg. of ascorbic acid.

Other vitamins and minerals can be incorporated, dependent upon the individual requirements. These medicaments can be added to the granulations by known methods for incorporation into the two-layered tablets of this invention.

Various pharmaceutically acceptable dyes may be used in the tablet of this invention to produce two-color and two-tone tablets. Pharmaceutically acceptable flavors 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.

The two-layered tablet of this invention possesses greater chemical stability of the ascorbic acid; has favorable size characteristics, lending itself to ease of administration; and is pleasant tasting and elegant.

The tablets of this invention are also illustrated in the attached drawing.

FIGURE 1Exploded outer side-view of the twolayered tablet. One of the layers contains the mannitol coated ascorbic acid core (1). The second layer contains the ferrous fumarate granulation compressed thereon (2).

FIGURE 2Cr0ss-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. The two granulations are clearly separated from each other by the mannitol coating.

The following'examples are illustrative of the processes and products of this invention and are not to be construed as limiting.

EXAMPLE 1 (A) Preparation of Tablet Cores Each core contains:

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 flavor mg 2.0

Granulating Solution Ethylcellulose mg 1.2 213 alcohol ml 0.05 Red dye, PD. and C mg 0.10

Lubrication Magnesium stearate, U.S.P mg 2.25 Talc, U.S.P mg 2.25

The ascorbic acid was blended with mannitol, flavor, sodium cyclamate and acacia. The resulting powder mixture was passed through a 40 mesh screen and then gran ulated with the ethylcellulose-dye-alcohol solution and finally with 213 alcohol. The wet granulation was passed through a 12 mesh screen and dried at 70 to 110 Fahrenheit for 8 hours. The dried granulation was passed through a 16 mesh screen. The lubricants were added and blended thoroughly.

(B) Preparation of Sugar Coating Each Mannitol coating contains:

Mannitol, NF "mg" 277.62 Methylcellulose, 400 cps, U.S.P mg 6.00 Sodium cyclamate, NF mg 2.40 Dried lemon flavor mg 3.83

Granulating Solution Purified water rnl 0.055 Yellow dye, PD. and C. mg 0.15

Lubrication Magnesium stearate, U.S.P mg 4.50 Talc, U.S.P mg 4.50

The mannitol, methylcellulose, sodium cyclamate and flavor were blended and passed through a 40 mesh screen, then granulated with the dye-water solution and finally with purified 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 mesh screen. The lubricants were added and blended thoroughly.

(C) Preparation of Ferrous Fumarate Layer Each ferrous fumarate layer contains:

Ferrous fumarate mg. 60.846 Mannitol, N.F mg 205.704 Methylcellulose, 400 cps mg 6.000 Sodium cyclamate, N.F mg 12.000 Dried spearmint flavor mg 6.25

Granulating Solution Purified 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, sodium cyclamate, and flavor were blended and passed through a mesh screen, then granulated with the dye-water solution and finally with purified water. The wet granulation was passed through a 12 mesh screen and thoroughly dried at 110 Fahrenheit for 12 hours. It was then passed through a 30 mesh screen. The lubricants were added and blended thoroughly.

(D) Compression of Layered Tablet The two layered tablets were compressed as follows:

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.

EXAMPLE 2 Using the procedure of Example 1, two-layered tablets, wherein one layer consisted of a compression coated core of ascorbic acid, were prepared containing 50 mg. of polyoxyethylene-polyoxypropylene copolymer wetting agent in the ferrous fumarate layer replacing 50 mg. of the mannitol.

EXAMPLE 3 Using the procedure of Example 1, two-layered tablets, wherein one layer consisted of a compression coated core of ascorbic acid, were prepared containing 25 mg. ascorbic acid per tablet in place of the 50 mg. of Example 1.

EXAMPLE 4 Using the procedure of Example 1, two layered tablets, wherein one layer consisted of a compression coated core of ascorbic acid, were prepared containing sodium ascorbate in amounts equivalent to about mg. ascorbic acid.

I EXAMPLE 5 Using the procedure of Example 1, two layered tablets, wherein one layer consisted of a compression coated core of ascorbic acid, were prepared containing ferrous fumarate in an amount equivalent to about 10 mg. of iron in place of the 60.846 mg. of ferrous fumarate (equivalent to 20 mg. of iron) in Example 1.

EXAMPLE 6 Using the procedure of Example 1, two layered tablets, wherein one layer consisted of "a compression coated core of ascorbic acid, were prepared containing ferrous sulfate in an amount equivalent to about 50 mg. of iron.

Having thus described our invention, we claim:

A chewable hematinic vitamin tablet form comprising 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 finished tablet, an inert compression-coated methylcellulosegranulated mannitol barrier coating completely surrounding said vitamin tablet core portion and a hemantinic granulation layer containing methylcellulosegranulated mannitol and a therapeutically acceptable ferrous iron compound, said chewable vitamin tablet form having the hematinic tablet layer compressed to one face of the mannitol-coated precompressed vitamin core portion.

References Cited in the file of this patent UNITED STATES PATENTS 2,410,110 Taylor Oct. 29, 1946 2,811,483 Alterno et al Oct. 29, 1957 2,822,317 Gulesich et al Feb. 4, 1958 2,887,436 Kloize et al May 19, 1959 2,939,820 Gerber et al. June 7, 1960 2,985,559 Coles May 23, 1961 2,996,431 Barry Aug. 15, 1961 3,019,169 Klumpp et al Jan. 30, 1962 3,048,526 Boswell Aug. 7, 1962 (Qther references on foiiowiug page) FOREIGN PATENTS 807,638 Great Britain Jan. 21, 1959 851,761 Great Britain Oct. 19, 1960 OTHER REFERENCES Atlas-Guide to Using Mannitol, N. F. as a Base in

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