The present invention relates to a stable nutritional supplement tablet comprising a novel triple coating of a seal coating layer, a film coating layer, an overcoating layer, and process of preparation thereof.
Nutrition plays a critical role in maintaining good health. Proper nutrition prevents dietary deficiencies, and also protects against the development of disease. Further proper nutrition plays an increasingly important role in helping the body cope physiological stress. For example, pregnancy and lactation are among the most nutritionally volatile and physiologically stressful periods and processes in the lifetimes of women. Specifically, vitamin and mineral needs are almost universally increased during these natural processes. These increased needs are almost always due to elevated metabolic demand, increased plasma volume, increased levels of blood cells, decreased concentrations of nutrients, and decreased concentrations of nutrient-binding proteins.
Vitamins or multivitamins and multimineral preparations, commonly known as nutritional supplements are designed to supplement the nutritional needs of individuals without or within physiologically stressful states. These nutritional supplements serve a vital role in protecting against poor nutrition and disease. More specifically, research has suggested that optimizing specific nutrients before, during, and after the physiological processes of pregnancy or lactation can have a profound, positive, and comprehensive impact upon the overall wellness of the developing and newborn child as well as the safety and health of the mother.
Numerous prior art references are directed towards the preparation and use of multivitamin and/or multimineral nutritional supplements. US 5,869,084 discloses a group of multivitamin and mineral supplements for women which are designed to meet the nutritional requirements for women at the various stages of their lives. US 5,494,678 discloses a group of multivitamin and mineral supplements for pregnant women which are designed to maximize fetal development and
maternal health during each trimester of pregnancy. US 4,684,534 discloses a quick-liquefying chewable tablet containing vitamins and carbohydrate-based agglomerate, which resists absorption of moisture but quickly liquefies and melts in the mouth once it has been chewed. US 4,725,427 discloses an effervescent vitamin-mineral granule preparation which is designed to be dissolved in water or another liquid to provide a nutritional and tasteful beverage.
However while formulating nutritional supplement in the form of a tablet, use of a coating becomes the perquisite to overcome the bitter taste of multivitamins. Since multivitamins are also susceptible to degradation, the coating composition should be such that prevents the multivitamin degradation from moisture, air etc. Further regulatory involvement in the area of nutritional fortification of foods requires that any coating composition be substantially free of questionable residues employed to implement such coating materials. Thus the coating agents, as well as the solvents employed to facilitate distribution of the coating agent, should preferably be on the GRAS (generally recognized as safe by the Food & Drug Administration) list. Additionally, formulating these nutritional supplement tablets under PFA Act (Prevention of Food Adulteration Act) also remains a challenge. Under this act, like all other excipients use of natural colors in the coating remains the preferred ones. But the choice of specific natural color for a nutritional supplement tablet remains the critical step for formulating a stable and acceptable dosage form.
We have now developed a novel coating composition comprising natural colors that prevent nutritional supplement from degradation as well as mask the unpleasant taste of multivitamins.
Hence in one general aspect there is provided a stable nutritional supplement
tablet comprising a triple coating composition of:
a seal coating layer comprising film forming water-soluble polymer;
a film coating layer comprising film forming water-soluble polymer and natural
pigment;
an overcoating layer comprising film forming water-soluble polymer.
In another general aspect there is provided a stable nutritional supplement tablet
comprising a triple coating composition of:
a seal coating layer comprising film forming water-soluble polymer;
a film coating layer comprising film forming water-soluble polymer and caramel
colorant;
an overcoating layer comprising film forming water-soluble polymer.
In another general aspect there is provided a process for the preparation of a stable nutritional supplement tablet comprising the steps of:
a) blending ginseng root extract and all the vitamins with one or more
pharmaceutically inert excipients,
b) optionally granulating the blend,
c) blending all the minerals with one or more pharmaceutically inert excipients,
d) optionally granulating the blend,
e) mixing the blend/granules with one or more pharmaceutically inert excipients,
f) compressing the blend with appropriate tooling to form tablet core,
g) applying the aqueous solution of film forming water-soluble polymer and one
or more coating additives over tablet core of step f) to form a seal coat,
h) applying the aqueous dispersion of film forming water-soluble polymer, natural
pigment and one or more coating additives over the seal coat to form a film coat,
and
i) applying the aqueous solution of film forming water-soluble polymer and one or
more coating additives over the film coat to form a overcoat.
The present invention provides stable nutritional supplement tablets for both prophylactic and therapeutic individual's states. Specifically, for example, the present invention relates to stable nutritional supplement tablets that can be used
to supplement the nutritional deficiencies observed in patients throughout physiologically stressful states such as, for example, pregnancy, lactation, and any disease states. Optimizing specific nutrients before, during, and after the physiological processes of pregnancy and lactation can have a profound, positive, and comprehensive impact on the overall wellness of the developing and newborn child as well as the safety and health of the mother. The compositions and methods of the present invention provide the means to optimize good health by utilizing vitamin and mineral nutritional supplementation. The compositions and methods of the present invention may comprise or use a combination of vitamins and minerals, in either chelated or non-chelated form, that work together with various metabolic systems and physiological responses of the human body. The specific triple coating composition having specific natural colourants provides stable dosage forms having improved taste or having the bitter taste masked. Further, as these tablets are quite larger in size, the uniformity of color achieved adds to the aesthetic value of the tablet, making it more consumer compliant.
The term "stable" as used herein refers to the physical appearance of tablet, in particular, color of the tablet.
The term "seal coating" as used herein describes the coating over the tablet core and the term "overcoating" as used herein describes the final coating over the intermediate film coating. Both the seal coating and overcoating act as a moisture barrier to prevent nutritional supplement from degradation. Both the seal coating and overcoating comprises one or more film forming water-soluble polymer and one or more coating additives. Both the seal coating and overcoating comprises from about 0.5 to about 2% w/w.
The term "film coating" as used herein describes the coating in between seal and overcoating layers. The film coating comprises film forming polymer, natural
pigment and one or more coating additives. The film coating comprises from about 2 to about 5% w/w.
Examples of film forming water-soluble polymers include hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol, polyvinylpyrrolidone (PVP), starch and derivatives thereof, hydroxypropyl cellulose, carboxymethyl cellulose, methyl cellulose, acrylic acid polymers, polymethacrylates, and the like.
The natural pigment may be selected from dry and edible, natural color pigments that at the present time do not require certification by the Food and Drug Administration since they utilize natural ingredients. Examples of natural pigments include caramel colorant, beta-carotene, canthaxanthin, chlorophyll, riboflavin, annatto, saffron, turmeric, in particular caramel colorant. Caramel colorant, is an amorphous, dark-brown material that may be produced by the controlled heat treatment of saccharine materials such as dextrose, invert sugar, lactose, malt syrup, molasses, sucrose, starch hydrolysates and fractions thereof, in the presence of small amounts of food grade acids, alkalis, or salts. Caramel colorants are exceptionally stable, tolerant of a wide range of physical and chemical environments, e.g. caramel colorant has good functionality across a wide range of pH from 2 to 10. Further caramel colorants help to prevent the degradation of multivitamins. The suppliers of caramel colorants include Sethness, D. D. Williamson and Valentine Agro Ltd. Alternatively commercially available coating composition comprising natural colorant and film forming polymers may be used. Specific examples include Instacoat® IC-N-055, Instacoat® IC-N-054, Instacoat® IC-N-058 and Instacoat® IC-U-6137.
The stable nutritional supplement tablet may comprise about 2.5 to about 3.5% w/w of ginseng extract powder and one or more vitamins such as about 0.3 to about 0.7% w/w of vitamin A, about 0.05 to about 0.15% w/w of vitamin B1, about 0.07 to about 0.2% w/w of vitamin B2, about 0.05 to about 0.15% w/w of vitamin B6, about 0.05 to about 0.15% w/w of vitamin B12, about 0.2 to about 1.5% w/w
of vitamin E, about 0.05 to about 0.2% w/w of folic acid, about 0.25 to about 0.75% w/w of calcium D-pantothenate, about 0.0015 to about 0.0035% w/w of biotin, about 1 to about 2% w/w of nicotinamide, about 2.5 to about 5% w/w of vitamin C and about 0.15 to about 0.25% w/w of vitamin D3 based on total tablet weight, and the like. The vitamins may be used in free form or in the form of corresponding salts. These may be coated, if desired.
The stable nutritional supplement tablet may further comprise one or more minerals such as about 0.8 to about 1.5% w/w of zinc oxide, about 0.008 to about 0.015% w/w of potassium iodide, about 1.75 to about 2.15% w/w of carbonyl iron, about 5 to about 15% w/w of light magnesium oxide, about 0.10 to about 0.60% w/w of magnesium sulphate, about 0.10 to about 0.20% w/w of cupric oxide, about 12 to about 18% w/w of calcium carbonate, about 30 to about 40% w/w of dibasic calcium phosphate, about 3.0 to about 7.0% w/w of potassium chloride, about 0.005 to about 0.015% w/w of chromic chloride, about 0.001 to about 0.007% w/w of sodium molybdate, about 0.005 to about 0.015% w/w of sodium selenate, about 0.001 to about 0.002% w/w of nickel sulphate, about 0.001 to about 0.002% w/w of sodium metavandate, about 0.13 to about 0.23% w/w of sodium borate, about 0.0005 to about 0.0016% w/w of stannus chloride, and the like.
The stable nutritional supplement tablet of the present invention may further comprise one or more "pharmaceutically acceptable excipients" selected from one or more of fillers, binders, disintegrants and lubricant/glidants.
Specific examples of fillers include lactose, microcrystalline cellulose, pregelatinized starch, calcium carbonate, calcium phosphate dibasic, calcium phosphate tribasic, calcium sulphate, kaolin, starch, and the like.
Specific examples of binders include methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, gelatin, gum arabic, ethyl
cellulose, polyvinyl alcohol, pullulan, pregelatinized starch, agar, tragacanth, sodium alginate, propylene glycol, and the like.
Specific examples of disintegrants include sodium carboxymethyl cellulose, low-substituted hydroxypropylcellulose L-HPC), sodium starch glycollate, carboxymethyl cellulose, calcium carboxymethyl cellulose, croscarmellose sodium, starch, partially pregelatinized starch, and the like.
Specific examples of lubricants/glidants include colloidal silicon dioxide, stearic acid, magnesium stearate, calcium stearate, zinc stearate, sodium stearyl fumarate, talc, hydrogenated castor oil, sucrose esters of fatty acid, microcrystalline wax, yellow beeswax, white beeswax, and the like.
The tablet core of the present invention may be prepared by wet granulation, dry granulation, direct compression, extrusion-spheronization or combination of any of these. The wet granulation process involves use of water or any other suitable solvent as granulating fluid. The dry granulation may involve use of roller compacter or any suitable technique. As vitamins are moisture sensitive, use of dry granulation or direction compression remains preferred, however if using coated vitamins, use of only direct compression remains preferred. For minerals, use of any formulating technique may be employed.
Coating additives may be selected from the group comprising of plasticizers, opacifiers, and the like. In addition to the above one or more pharmaceutically acceptable excipients may be also be included as coating additives.
Specific examples of plasticizers include triethylcitrate, acetylated triacetin, tributylcitrate, glyceroltributyrate, monoglyceride, rape oil, olive oil, sesame oil, acetyltributylcitrate, acetyltriethylcitrate, glycerin sorbitol, diethyloxalate, diethyl phthalate, diethylmalate, diethylfumarate, dibutylsuccinate, diethylmalonate,
dioctylphthalate, dibutylsebacate, glycerin, polyethylene glycol 8000, triacetin, lecithin, and the like.
Specific examples of opacifiers include talc, calcium carbonate, behenic acid, cetyl alcohol and the like.
The core tablets may be coated with solution/suspension of film forming polymers and coating additives with or without natural pigment using any conventional coating technique known in the prior art such as spray coating in a conventional coating pan or fluidized bed processor; dip coating or compression coating.
In one of the embodiments, the stable nutritional supplement tablet may be prepared by a process comprising the steps of;
i) blending ginseng root extract and all the vitamins with one or more
pharmaceutically inert excipients, ii) compacting the blend of step (i), iii) screening the compact of step (ii) to form granules, iv) blending all the minerals with one or more pharmaceutically inert
excipients, v) granulating the blend of step (iv) with a granulating fluid to form
granules, vi) mixing the granules of steps (iii) and (v) with one or more
pharmaceutically inert excipients, vii) compressing the blend with appropriate tooling to form tablet cores, viii) preparing an aqueous solution of film forming water soluble polymer
and one or more coating additives, ix) applying the aqueous solution of step viii) over the tablet core of step
vii) to form a seal coat, x) preparing the aqueous dispersion of film forming water-soluble
polymer, caramel pigment and one or more coating additives,

xi) applying the aqueous dispersion of step x) over the seal coat layer to
form a film coat;, xii) preparing an aqueous solution of film forming water soluble polymer
and one or more coating additives, and xiii) applying the aqueous solution of step xii) over the film coat to form an
overcoat.
In another embodiment, the stable nutritional supplement tablet may be prepared by a process comprising the steps of;
i) blending ginseng root extract and one or more vitamins with one or
more pharmaceutically inert excipients, ii) compacting the blend of step (i), iii) screening the compact of step (ii) to form granules, iv) blending all the minerals with one or more pharmaceutically inert
excipients, v) granulating the blend of step (iv) with a granulating fluid to form
granules, vi) blending one or more vitamins with one or more pharmaceutically inert
excipients, vii) mixing the granules of steps (iii) and (v), and blend of step (vi) with one
or more pharmaceutically inert excipients, viii) compressing the blend with appropriate tooling to form tablet cores, ix) preparing an aqueous solution of film forming water soluble polymer
and one or more coating additives, x) applying the aqueous solution of step ix) over the tablet core of step
viii) to form a seal coat, xi) preparing the aqueous dispersion of film forming water-soluble
polymer, caramel pigment and one or more coating additives, xii) applying the aqueous dispersion of step xi) over the seal coat layer to
form a film coat,
xiii) preparing an aqueous solution of film forming water soluble polymer
and one or more coating additives, and xiv) applying the aqueous solution of step xiii) over the film coat to form an
overcoat
The invention is further illustrated by the following examples, which is for illustrative purpose only and should not be construed as limiting the scope of the invention in any way.

(Table Removed)
Preparation of Blend A
1. Vitamin A, Vitamin B1, Vitamin B2, Vitamin B6, Vitamin B12, Vitamin E, folic acid, calcium pantothenate, biotin, nicotinamide, ginseng root extract and colloidal silicon dioxide were sifted through BSS #22 mesh and mixed
2. Microcrystallines cellulose and croscarmellose sodium were sifted through BSS#44 mesh.
3. Materials of step 2 was added to the material of step 1 and mixed in DCB for 15 minutes.
4. Magnesium stearate was sifted through BSS #44 mesh.
5. Material of step 4 was added to the material of step 3 and mixed in DCB for 5 minutes.
6. The material of step 5 was compacted on a roller compactor.
7. The compacts of step 6 were screened through BSS #22 mesh.
8. The material of step 7 was screened through BSS #44 mesh and the material collected below this mesh was recompacted.
9. The compacts of step 8 were crushed again and screened through BSS#22 mesh and added to the remaining granules of step 8.
10. The material of step 9 was transferred to triple laminated polybag.
Preparation of Blend B
1. Zinc oxide, potassium iodide, carbonyl iron, magnesium sulfate, cupric oxide, calcium carbonate, potassium chloride, chromic chloride, sodium molybdate, sodium selenate, nickel sulphate, sodium meta vanadate, sodium borate and stannous chloride were sifted through BSS#22 mesh and mixed in a geometric order.
2. Microcrystalline cellulose and croscarmellose sodium were sifted through BSS#22 mesh.
3. Dibasic calcium phosphate and light magnesium oxide were sifted through BSS#22 mesh.
4. The materials of steps 2 and 3 were added to material of step 4 and mixed for 15 minutes in RMG.
5. PVP K-30 was dissolved in purified water to get clear solution.
6. The material of step 4 was granulated with the binder solution of step 5.
7. The wet mass was dried till the LOD was 2-3% w/w.
8. The dried material was passed through BSS#22 mesh.
9. The material of step 8 was transferred to triple laminated polybag.
Preparation of Blend C
1. Vitamin C and Vitamin D3, colloidal silicon dioxide, microcrystalline cellulose and croscarmellose sodium were sifted through BSS#22 mesh and mixed in a geometric order.
2. Magnesium stearate was sifted through BSS#44 mesh and collected separately.
Preparation of Final Tablets
1. The material of blend A was mixed with material of blend C (step 1 for the preparation of Blend C) for 15 minutes.
2. The material of blend B was added to the above material of step 1 and mixed for 10 minutes.
3. Sifted magnesium stearate of blend C (step 2 for the preparation of Blend C) was added to the above material of step 2 and mixed for 5 minutes.
4. The final blend of step 3 was compressed with approved tooling.
Film Coating
Seal Coating
1. Opadry II 85F19250 clear was dissolved in purified water to prepare a coating solution.
2. The compressed tablets were coated using above solution to a weight gain of 1%.
Film Coating
1. Instacoat IC-N-055 Brown was dispersed in purified water to prepare the coating solution.
2. The above seal coated tablets were coated using above solution to a weight gain of 2.5%.
Over Coating
1. Opadry II 85F19250 clear was dissolved in purified water to prepare a coating solution.
2. The above film coated tablets were coated using above solution to a weight gain of 1.0%.
Stability Data
The physical appearance of tablet, in particular, color of the tablet as obtained from the above example, is observed under different conditions, as mentioned below in table 1. (Table Removed)

WE CLAIM:
1. A stable nutritional supplement tablet comprising a triple coating
composition of:
a seal coating layer comprising film forming water-soluble polymer,
a film coating layer comprising film forming water-soluble polymer and
natural pigment, and
an overcoating layer comprising film forming water-soluble polymer.
2. The stable nutritional supplement tablet of claim 1, wherein the film forming water-soluble polymer is selected from the group consisting of hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol, polyvinylpyrrolidone (PVP), starch and derivatives thereof, hydroxypropyl cellulose, carboxymethyl cellulose, methyl cellulose, acrylic acid polymers and polymethacrylates.
3. The stable nutritional supplement tablet of claim 1, wherein the natural pigment is selected from the group consisting of caramel colorant, beta-carotene, canthaxanthin, chlorophyll, riboflavin, annatto, saffron and turmeric.
4. The stable nutritional supplement tablet of claim 1, wherein the seal coating comprises about 0.5 to about 2% w/w.
5. The stable nutritional supplement tablet of claim 1, wherein the film coating comprises about 2 to about 5% w/w.
6. The stable nutritional supplement tablet of claim 1, wherein the overcoating comprises about 0.5 to about 2% w/w.
7. The stable nutritional supplement tablet of claim 1, wherein the tablet is
prepared by a process comprising the steps of;
a) blending ginseng root extract and all the vitamins with one or more pharmaceutically inert excipients,
b) optionally granulating the blend,
c) blending all the minerals with one or more pharmaceutically inert
excipients,
d) optionally granulating the blend,
e) mixing the blend/granules with one or more pharmaceutically inert
excipients,
f) compressing the blend with appropriate tooling to form tablet core,
g) applying the aqueous solution of film forming water-soluble polymer and
one or more coating additives over tablet core of step f) to form a seal
coat,
h) applying the aqueous dispersion of film forming water-soluble polymer, natural pigment and one or more coating additives over the seal coat to form a film coat
i) applying the aqueous solution of film forming water-soluble polymer and one or more coating additives over the film coat to form an overcoat.
8. The stable nutritional supplement tablet of any of the preceding claims wherein the pharmaceutically acceptable excipients is selected from the group consisting of fillers, binders, disintegrants and lubricants/glidants.
9. The stable nutritional supplement tablet of any of the preceding claims wherein the coating additives may be selected from the group consisting of plasticizers and opacifiers.
10. A stable nutritional supplement tablet and process of coating thereof substantially as described herein.