U.S. patent application number 09/877850 was filed with the patent office on 2001-11-01 for soft chewable multivitamin tablet comprising separated active ingredients.
This patent application is currently assigned to SAM-A-PHARMACEUTICALS CO., LTD.. Invention is credited to Han, Yoon Dong, Park, Jong Bum.
Application Number | 20010036468 09/877850 |
Document ID | / |
Family ID | 19545208 |
Filed Date | 2001-11-01 |
United States Patent
Application |
20010036468 |
Kind Code |
A1 |
Han, Yoon Dong ; et
al. |
November 1, 2001 |
Soft chewable multivitamin tablet comprising separated active
ingredients
Abstract
The present invention provides an improved soft chewable
multivitamin tablet in which vitamin C is separated from calcium
pantothenate and/or minerals such as iron, copper, zinc and
mixtures thereof in a core or multilaminate form and a process for
preparing the same. The soft chewable multivitamin tablet of the
present invention maintains its stability over a long-storage time
in terms of the content and potency of vitamins while overcoming
the problems of incompatibility, bad mouthfeel and
palatability.
Inventors: |
Han, Yoon Dong; (Seoul,
KR) ; Park, Jong Bum; (Anyang, KR) |
Correspondence
Address: |
DARBY & DARBY P.C.
805 Third Avenue
New York
NY
10022
US
|
Assignee: |
SAM-A-PHARMACEUTICALS CO.,
LTD.
|
Family ID: |
19545208 |
Appl. No.: |
09/877850 |
Filed: |
June 8, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09877850 |
Jun 8, 2001 |
|
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09314552 |
May 19, 1999 |
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Current U.S.
Class: |
424/405 ;
424/630; 424/643; 424/646 |
Current CPC
Class: |
A23L 33/15 20160801;
Y10S 514/905 20130101; A23G 3/368 20130101; A61K 33/34 20130101;
A23G 3/54 20130101; Y10S 514/96 20130101; Y10S 514/904 20130101;
A61K 9/0056 20130101; A61K 45/06 20130101; A23V 2002/00 20130101;
A61K 9/209 20130101; A23G 3/40 20130101; Y10S 514/961 20130101;
Y10S 514/97 20130101; A61K 33/34 20130101; A61K 2300/00 20130101;
A23V 2002/00 20130101; A23V 2250/1578 20130101; A23V 2250/161
20130101; A23V 2002/00 20130101; A23V 2250/702 20130101; A23V
2250/704 20130101; A23V 2250/708 20130101; A23V 2250/71 20130101;
A23V 2250/712 20130101; A23V 2002/00 20130101; A23V 2250/60
20130101; A23V 2250/1614 20130101; A23V 2250/032 20130101; A23V
2250/1578 20130101; A23V 2250/21 20130101; A23V 2002/00 20130101;
A23V 2250/628 20130101; A23V 2250/61 20130101; A23V 2250/612
20130101; A61K 33/34 20130101; A61K 33/32 20130101; A61K 33/26
20130101; A61K 31/375 20130101; A61K 31/195 20130101 |
Class at
Publication: |
424/405 ;
424/646; 424/643; 424/630 |
International
Class: |
A61K 033/34; A61K
033/32; A61K 033/26 |
Foreign Application Data
Date |
Code |
Application Number |
Jul 25, 1998 |
KR |
98-30049 |
Claims
What is claimed is:
1. A soft chewable multivitamin tablet comprising active
ingredients, sugars, fatty materials and emulsifiers, wherein the
improvement comprises that vitamin C is separated from calcium
pantothenate, and/or minerals of iron, copper, zinc and mixtures
thereof.
2. The soft chewable multivitamin tablet of claim 1, wherein the
active ingredients are contained in the tablet in an amount of 0.1
to 50 wt %.
3. The soft chewable multivitamin tablet of claim 1, wherein the
active ingredients comprise: vitamin selected from the group
consisting of vitamin A, vitamin B.sub.1, vitamin B.sub.2, vitamin
B.sub.6, vitamin B.sub.12, vitamin C, vitamin D, vitamin E, vitamin
K, nicotinamide, folic acid, calcium pantothenate, biotin and
mixtures thereof; mineral supplement selected from the group
consisting of calcium, calcium carbonate, calcium phosphate,
magnesium, magnesium carbonate, magnesium glycerophosphate,
manganese, potassium, lecithin, iron, copper, zinc, phosphorus and
mixtures thereof; and, herbal drug selected from the group
consisting of hippophae rhamnoides ext., pollen, Garcinia,
Echinaceae, ginsenoside ext., Ginkgo biloba ext., blueberry,
hawthorn ext., acanthopanax ext., aloe ext., Cardus marianus ext.
and mixtures thereof.
4. The soft chewable multivitamin tablet of claim 1, wherein the
sugars are contained in the tablet in an amount of 50 to 90 wt
%.
5. The soft chewable multivitamin tablet of claim 1, wherein the
sugars are selected from the group consisting of white sugar, corn
syrup, sorbitol (solution), maltitol (syrup), oligosaccharide,
isomaltooligosaccharide, fructose, lactose, glucose, lycasin,
xylitol, lactitol, erythritol, mannitol, isomaltose, polydextrose,
dextrin and mixtures thereof.
6. The soft chewable multivitamin tablet of claim 1, wherein the
fatty materials are contained in the tablet in an amount of 3 to 15
wt %.
7. The soft chewable multivitamin tablet of claim 1, wherein the
fatty materials are vegetable oil or animal oil.
8. The soft chewable multivitamin tablet of claim 7, wherein the
vegetable oil is selected from the group consisting of palm oil,
palm hydrogenated oil, corn germ hydrogenated oil, castor
hydrogenated oil, cotton-seed oil, olive oil, peanut oil, palm
olein oil, Cacao fat, margarine, butter, shortening and palm
stearin oil.
9. The soft chewable multivitamin tablet of claim 7, wherein the
animal oil is selected from the group consisting of refined oil and
refined lard whose melting point ranges from 30 to 42.degree.
C.
10. The soft chewable multivitamin tablet of claim 1, wherein the
emulsifiers are contained in the tablet in an amount of 0.01 to 5.0
wt %.
11. The soft chewable multivitamin tablet of claim 1, wherein the
emulsifiers are selected from the group consisting of glycerin
fatty acid ester, sorbitan monostearate, sucrose fatty acid ester,
lecithin and mixtures thereof.
12. The soft chewable multivitamin tablet of claim 1, wherein the
multivitamin tablet further comprises fondant, gums, flavors or
mixtures thereof.
13. The soft chewable multivitamin tablet of claim 12, wherein the
fondant is contained in the tablet in an amount of 3 to 20 wt
%.
14. The soft chewable multivitamin tablet of claim 12, wherein the
gums are contained in the tablet in an amount of 0.1 to 5.0 wt
%.
15. The soft chewable multivitamin tablet of claim 12, wherein the
gums are selected from the group consisting of gelatin, agar,
arabic gum, guar gum and carrageenan.
16. The soft chewable multivitamin tablet of claim 12, wherein the
flavors are selected from the group consisting of strawberry
flavor, tutti fruity flavor, orange flavor, banana flavor and mint
flavor.
17. The soft chewable multivitamin tablet of claim 1, wherein a
stabilizer is further added to the vitamin C.
18. The soft chewable multivitamin tablet of claim 17, wherein the
stabilizer is added to the vitamin C 100 parts in an amount of 10
to 200 parts by weight.
19. The soft chewable multivitamin tablet of claim 17, wherein the
stabilizer is citric acid or sodium citrate.
20. The soft chewable multivitamin tablet of claim 19, wherein the
citric acid is separated from calcium pantothenate.
21. The soft chewable multivitamin tablet of claim 1, wherein
sodium citrate is further added to the calcium pantothenate.
22. The soft chewable multivitamin tablet of claim 1, wherein the
multivitamin tablet is a core or multilaminate form.
23. A process for preparing a soft chewable multivitamin tablet
which comprises the steps of: (i) dissolving and concentrating
sugars in a concentrating tank at a temperature of 120 to
135.degree. C., cooling the concentrated sugars to a temperature of
80 to 100.degree. C., adding a molten mixture of fatty materials
and emulsifiers, and kneading to a temperature of 60 to 80.degree.
C., adding and thoroughly kneading an active ingredient of vitamin
C and the other active ingredients except calcium pantothenate
and/or minerals such as iron, copper, zinc and mixtures thereof, or
calcium pantothenate and/or the said minerals and cooling to obtain
a kneaded mixture; (ii) dissolving active ingredients which are
different from those contained in the kneaded mixture, together
with sugars and a stabilizer at a temperature of 40 to 60.degree.
C. to obtain a dispersed material; and, (iii) extruding, rope
sizing and tabletting the kneaded mixture and the dispersed
material in a separate manner to give a soft chewable multivitamin
tablet.
24. The process for preparing a soft chewable multivitamin tablet
of claim 23, wherein the soft chewable multivitamin tablet is
prepared in a core or multilaminate form.
25. The soft chewable multivitamin tablet of claim 24, wherein the
soft chewable multivitamin tablet having a core is prepared by
centerfilling the dispersed material for core part to the kneaded
mixture for outershell.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to a soft chewable
multivitamin tablet, more specifically, to an improved soft
chewable multivitamin tablet in which vitamin C is separated from
calcium pantothenate, and/or minerals such as iron, copper, zinc
and mixtures thereof in a core or multilaminate form and a process
for preparing the same.
BACKGROUND OF THE INVENTION
[0002] In general, tablets are prepared by compression of a mixture
of active ingredients and pharmaceutically acceptable carriers such
as diluting agents. However, the hard nature of conventional
tablets does not allow children and the old to take them easily. In
this connection, several approaches have been made to prepare
tablets having softer mouthfeel in an attempt to overcome said
problems and to facilitate easy taking for children and the elderly
people.
[0003] For example, U.S. Pat. No. 4,327,076 discloses a chewable
tablet comprising Premix I (pretreated fat composition containing
fatty materials, fat-sorbing materials, tabletting binders,
antioxidants, flavors and colorants), Premix II (pretreated active
ingredient composition containing antacids, oil binders,
emulsifiers, flavors and colorants) and Premix III (pretreated
direct compression tabletting aids containing tabletting binders
and flavors). However, the prior art chewable tablet has revealed
shortcomings as followings: the tablet is uncomfortable to take,
because of its bad mouthfeel and palatability; and, an
intermediate-type tablet having the characters of hard tablet and
soft tablet is produced, since individually prepared Premix I,
Premix II and Premix III are simply mixed and tabletted.
[0004] Moreover, many multivitamin tablets developed so far are
proven to be less satisfactory in the senses that: they have
worries of the incompatibility owing to the chemical natures of
vitamins or minerals in the tablet containing vitamin complexes,
multivitamins-minerals or natural products; and, they revealed
undesirable aspects of lowering the content and potency of active
ingredients over a long-storage time.
[0005] Under the circumstances, there are strong reasons for
exploring and developing alternative soft chewable multivitamin
tablet which can avoid the chemical interactions among the various
vitamins to cause incompatibility while maintaining pleasant
mouthfeel and palatable taste.
SUMMARY OF THE INVENTION
[0006] The present inventors have made an effort to solve the said
problems by partitioning active ingredients whose potencies are
affected by the incompatibility, and formulated an improved soft
chewable multivitamin tablet in which one component of vitamin C is
separated from the other components of calcium pantothenate and/or
minerals to maintain a more stabilized pharmaceutical activity over
a long-storage time.
[0007] A primary object of the present invention is, therefore, to
provide a soft chewable multivitamin tablet whose active ingredient
of vitamin C is separated from calcium pantothenate, and/or
minerals such as iron, copper, zinc and mixtures thereof in a core
or multilaminate form.
[0008] The other object of the invention is to provide a process
for preparing the soft chewable multivitamin tablet which comprises
separated active ingredients.
BRIEF DESCRIPTION OF DRAWINGS
[0009] The above and the other objects and features of the present
invention will become apparent from the following description given
in conjunction with the accompanying drawings, in which:
[0010] FIG. 1 is a cross-sectional view of a core-type soft
chewable multivitamin tablet of the present invention.
[0011] FIG. 2(A) is a perspective view of a double-layered soft
chewable multivitamin tablet of the invention.
[0012] FIG. 2(B) is a perspective view of a three-layered soft
chewable multivitamin tablet of the invention.
DETAILED DESCRIPTION OF THE INVENTION
[0013] A soft chewable multivitamin tablet of the present invention
comprises active ingredients, sugars, fatty materials and
emulsifiers, wherein an active ingredient of vitamin C is separated
from calcium pantothenate, and/or minerals such as iron, copper,
zinc and mixtures thereof.
[0014] The soft chewable multivitamin tablet of the invention is
formulated by a process which comprises the steps of:
[0015] (i) dissolving and concentrating sugars in a concentrating
tank at a temperature of 120 to 135.degree. C., cooling the
concentrated sugars to a temperature of 80 to 100.degree. C.,
adding a molten mixture of fatty materials and emulsifiers, and
kneading to a temperature of 60 to 80.degree. C., adding and
thoroughly kneading an active ingredient of vitamin C and the other
active ingredients except calcium pantothenate and/or minerals such
as iron, copper, zinc and mixtures thereof, or calcium pantothenate
and/or the said minerals, and cooling to obtain a kneaded
mixture;
[0016] (ii) dissolving active ingredients which are different from
those contained in the kneaded mixture, together with sugars and a
stabilizer at a temperature of 40 to 60.degree. C. to obtain a
dispersed material; and,
[0017] (iii) extruding, rope sizing and tabletting the kneaded
mixture and the dispersed material in a separate manner to give a
soft chewable multivitamin tablet.
[0018] A soft chewable multivitamin tablet of the invention is
explained in more detail as below.
[0019] A soft chewable multivitamin tablet of the invention
comprises active ingredients, sugars, fatty materials and
emulsifiers, and may further comprise fondant, gums, flavors,
stabilizers and the like to improve mouthfeel and palatability and
to stabilize the active ingredients. The active ingredients are
contained in a soft chewable multivitamin tablet in an amount of
0.1 to 5 wt %, preferably 0.1 to 25 wt %, which includes vitamins
such as vitamin A, vitamin B.sub.1, vitamin B.sub.2, vitamin
B.sub.6, vitamin B.sub.12, vitamin C, vitamin D, vitamin E, vitamin
K, nicotinamide, folio acid, calcium pantothenate, biotin and
mixtures thereof; mineral supplements such as calcium, calcium
carbonate, calcium phosphate, magnesium, magnesium carbonate,
magnesium glycerophosphate, manganese, potassium, lecithin, iron,
copper, zinc, phosphorus and mixtures thereof; and, herbal rugs
such as hippophae rhamnoides ext., pollen, Garcinia, Echinaceae,
ginsenoside ext., Ginkgo biloba ext., blueberry, hawthorn ext.,
acanthopanax ext., aloe ext., Cardus marianus ext. and mixtures
thereof.
[0020] Further, the soft chewable multivitamin tablet may comprise
citric acid or sodium citrate as a stabilizer for vitamin C in a
level of 10 to 200 parts, preferably 20 to 80 parts, by weight of
the vitamin C 100 parts, whereby vitamin C becomes stabilized to
give synergic effect, where the stabilizer plays a dual role as a
chelating agent and pH controller as well. In this connection, if
the level of stabilizer is lower than the said range, the
stabilization cannot be realized, or if it is higher than the said
range, the chelation is not realized and pH will rise or fall as
well.
[0021] In addition, the present invention includes a multivitamin
tablet which further comprises sodium citrate for the stabilization
of an active ingredient of calcium pantothenate, where calcium
pantothenate is stabilized by forming a microenvironment of pH 6 to
7 to permit a long-term storage. Citric acid for stabilizing
vitamin C should also be separated from calcium pantothenate.
[0022] In the soft chewable multivitamin tablet of present
invention, sugars such as white sugar, corn syrup, sorbitol
(solution), maltitol (syrup), oligosaccharide,
isomaltooligosaccharide, fructose, lactose, glucose, lycasin,
xylitol, lactitol, erythritol, mannitol, isomaltose, polydextrose,
dextrin and mixtures thereof are added to improve mouthfeel and
palatability, in an amount of 50 to 90 wt %, preferably 75 to 85 wt
% by weight of the whole tablet.
[0023] A soft chewable multivitamin tablet of the invention also
comprises fatty materials in an amount of 3 to 15 wt %, preferably
5 to 7 wt %, by weight of the whole tablet, to prevent separation
phenomenon and improve mouthfeel. The fatty materials include
vegetable oil such as palm oil, palm hydrogenated oil, corn germ
hydrogenated oil, castor hydrogenated oil, cotton-seed oil, olive
oil, peanut oil, palm olein oil, Cacao fat, margarine, butter,
shortening and palm stearin oil, or animal oil such as refined oil
and refined lard whose melting point ranges from 30 to 42.degree.
C.
[0024] To prevent the separation phenomenon and stickiness
appearing in the conventional soft chewable tablets and to
facilitate conversion of the active ingredients to emulsion or
suspension upon taking, the soft chewable multivitamin tablet
further comprises emulsifiers such as glycerin fatty acid ester,
sorbitan monostearate, sucrose fatty acid ester, lecithin and
mixtures thereof, in an amount of 0.01 to 5.0 wt %, preferably 0.05
to 2.0 wt % by weight of the whole tablet. If the level of
emulsifier is lower or higher than the said range, the
emulsification cannot be realized, or wax value will rise.
[0025] To improve the chewiness of the tablet, the soft chewable
multivitamin tablet may comprise fondant in an amount of 3 to 20 wt
%, preferably 5 to 15 wt %, or gums such as gelatin, agar, arabic
gum, guar gum, and carrageenan in an amount of 0.1 to 5 wt %, by
weight of the whole tablet. In addition, flavors such as strawberry
flavor, tutti fruity flavor, orange flavor, banana flavor and mint
flavor may be further included to improve flavorance of the
multivitamin tablet.
[0026] A process for preparing a soft chewable multivitamin tablet
of the present invention is further illustrated as below, where the
present inventors separated an active ingredient of vitamin C from
the others in a core or multilaminate form, since the contact
between one component of vitamin C and the other component of
calcium pantothenate, iron, copper, zinc and mixtures thereof, may
bring about incompatibility and loss of content and potency of some
vitamins.
[0027] Preparation of a Soft Chewable Multivitamin Tablet Having a
Core
[0028] Sugars and water are mixed, dissolved, and concentrated by
heating to a temperature of 120 to 135.degree. C. under a reduced
pressure of -100 to -500 mmHg in a concentrating tank and cooled to
a temperature of 90 to 100.degree. C., where concentration at a
high temperature over 135.degree. C. is undesirable because sugars
become degraded, conversed, browned or hardened. To the concentrate
are added a molten mixture of fatty materials with emulsifier, and
kneaded to a temperature 60 to 80.degree. C. and an active
ingredient of vitamin C and the other active ingredients except
calcium pantothenate and/or minerals such as iron, copper, zinc and
mixtures thereof, or calcium pantothenate and/or the said minerals,
are added and thoroughly kneaded, and then tempered to a
temperature of 40 to 50.degree. C. to obtain a kneaded mixture for
outer shell.
[0029] On the other hand, sugars, stabilizers and an active
ingredient of vitamin C, or the other active ingredients of calcium
pantothenate and/or minerals such as iron, copper, zinc and
mixtures thereof, which are different from the components contained
in the outer shell, are dissolved at a temperature of 40 to
60.degree. C. to obtain a dispersion for core part.
[0030] Finally, extruding, rope sizing and tabletting the kneaded
mixture for outer shell and the dispersion for core part are
carried out to give a soft chewable multivitamin tablet in a core
form (see: FIG. 1).
[0031] Preparation of a Multilaminated Soft Chewable Multivitamin
Tablet
[0032] Sugars and water are mixed, dissolved and concentrated by
heating to a temperature of 120 to 135.degree. C. under a reduced
pressure of -100 to -500 mmHg in a concentrating tank and cooled to
a temperature of 90 to 100.degree. C. To the concentrate are added
a molten mixture of fat with emulsifier, and kneaded to a
temperature of 60 to 80.degree. C., and gums, flavors, stabilizers
and an active ingredient of vitamin C and the other active
ingredients except calcium pantothenate and/or minerals such as
iron, copper, zinc and mixtures thereof, are added and thoroughly
kneaded, and then tempered to a temperature of 40 to 50.degree. C.
to obtain a kneaded mixture of vitamin C layer.
[0033] Then, a kneaded mixture for multivitamins-minerals layer is
prepared in a similar manner as in the layer of vitamin C.
[0034] Finally, the kneaded mixture for vitamin C layer and
multivitamins-minerals layer are subjected to an extruder with two
inlets (one for the kneaded mixture for the vitamin C layer and the
other for the kneaded mixture for the multivitamins-minerals
layer), extruded and cooled to give a soft chewable multivitamin
tablet in a multilaminate form (see: FIGS. 2A and 2B).
[0035] The present invention is further illustrated by the
following examples, which should not be taken to limit the scope of
the invention.
EXAMPLE 1
A Soft Chewable Multivitamin Tablet Having a Core of Calcium
Pantothenate and an Outer Shell Containing Multi-Vitamins
[0036] White sugar, corn syrup, lactose and water whose contents
are shown in Table 1, were mixed, concentrated at 130.degree. C.
and then cooled to 90.degree. C. To the concentrated solution were
added a molten mixture of hydrogenated vegetable oil with glycerin
fatty acid ester and sorbitan monostearate which had been
preliminarily prepared, and kneaded to a temperature of 70.degree.
C. Then, fondant, gelatin solution, tutti fruity flavor and active
ingredients of multi-vitamins whose contents are shown in Table 1,
were added to the above mixture, and thoroughly kneaded to a
temperature of 40.degree. C. to give a kneaded mixture for outer
shell. Subsequently, sodium citrate and calcium pantothenate were
added to lycasin in a ratio shown in Table 2, dissolved and then
fruit juice powder was added and thoroughly dispersed to give a
core dispersion of pH 7. Thereafter, the said kneaded mixture for
an outer shell maintained at a temperature of 40.degree. C. was
subjected to an extruder equipped with a center filling device, to
obtain cylindrical outer shell of a proper width. Then, the core
dispersion was pumped into the center of outershell by the aid of
centerfilling device. Finally, a core-type soft chewable
multivitamin tablet of 4 g was prepared, after extruding, rope
sizing and tabletting, and packaged in a sealed form.
1TABLE 1 The composition of an outer shell in a soft chewable
multivitamin tablet Component Content Sugar white sugar 1,140 mg
corn syrup 1,400 mg lactose 175 mg Fatty Material hydrogenated
vegetable 260 mg Emulsifier glycerin fatty acid ester 10 mg
sorbitan monostearate 3 mg Fondant 480 mg Gum gelatin solution 14
mg Flavorant tutti fruity flavor 6 mg Water 130 mg Active
Ingredient vitamin A 1,000IU vitamin B.sub.1 0.65 mg vitamin
B.sub.2 0.75 mg vitamin B.sub.6 0.90 mg vitamin B.sub.12 0.002 mg
vitamin C (96% granule) 20.83 mg vitamin D.sub.3 115IU nicotinamide
5.4 mg tocopherol acetate 5.0 mg folic acid 0.2 mg calcium
phosphate 20 mg magnesium 10 mg lecithin 3.33 mg hippophae
rhamnoides ext. 6 mg
[0037]
2TABLE 2 The composition of a core part in a soft chewable
multivitamin tablet Component Content (mg) Sugar lycasin 450
Stabilizer sodium citrate 12 Active Ingredient calcium pantothenate
3 Fruit Juice Powder 50
EXAMPLE 2
A Soft Chewable Multivitamin Tablet Having a Core of Calcium
Pantothenate and an Outer Shell Containing Multi-Vitamins and
Citric Acid
[0038] A soft chewable tablet having a core of calcium pantothenate
and an outer shell of multi-vitamins and citric acid was prepared
in an analogous manner as in Example 1, with an exception of adding
12.5 mg of citric acid to the multi-vatamins component of the outer
shell.
EXAMPLE 3
A Soft Chewable Multivitamin Tablet Having a Core of Calcium
Pantothenate and an Outer Shell Containing Multi-Vitamins and
Citric Acid
[0039] A soft chewable tablet having a core of calcium pantothenate
and an outer shell of multi-vitamins and citric acid was prepared
in an analogous manner as in Example 1, with the exceptions of
adding 12.5 mg of citric acid to the multi-vitamins component of
the outer shell and replacing lycasin with sorbitol solution.
EXAMPLE 4
A Sucrose-Free Soft Chewable Multivitamin Tablet Having a Core of
Vitamin C and an Outer Shell Containing Multi-Vitamins
[0040] corn syrup, lycasin, mannitol, sorbitol solution, lactose
and water whose contents are shown in Table 3, were mixed,
concentrated at 130.degree. C. and then cooled to 90.degree. C. To
the concentrated solution were added a molten mixture of
hydrogenated vegetable oil with lecithin and span 60, which had
been preliminarily prepared and kneaded to a temperature of
70.degree. C. Then, gelatin solution, strawberry flavor and active
ingredients were added to the above mixture, and thoroughly
kneaded, and then a kneaded material was prepared to have a
material temperature of 40.degree. C. through tempering process.
Subsequently, an active ingredient of vitamin C and citric acid,
fruit juice powder and tutti fruity flavor were added and
thoroughly dispersed to lycasin in accordance with the contents
shown in Table 4 to give a homogeneous core dispersion. Thereafter,
the said kneaded mixture for an outer shell maintained at a
temperature of 40.degree. C. was subjected to an extruder equipped
with a center filling device, to obtain cylindrical outer shell of
a proper width. Then, the core dispersion was pumped into the
center of outershell by the aid of center filling device. Finally,
a core-type multivitamin tablet of 4 g was prepared, after
extruding, rope sizing and tabletting, and packaged in a sealed
form.
3TABLE 3 The composition of an outer shell in a soft chewable
multivitamin tablet Component Content (mg) Sugar corn syrup 1,300
lycasin 1,000 mannitol 500 sorbitol solution 300 lactose 150 Fatty
Material hydrogenated vegetable 260 Emulsifier lecithin 5 Span 60
2.5 Gum gelatin solution 12 Flavorant strawberry flavor 10 Water
150 Active Ingredient vitamin A 2 vitamin B.sub.1 0.65 vitamin
B.sub.2 0.75 vitamin B.sub.6 0.90 0.1% vitamin B.sub.12 2 vitamin
D.sub.3 1.15 tocopherol 5 folic acid 0.2 nicotinamide 5.4 calcium
pantothenate 3 calcium phosphate 20 magnesium 10 lecithin 3.33
hippophae rhamnoides ext. 6
[0041]
4TABLE 4 The composition of a core part in a soft chewable
multivitamin tablet Component Content (mg) Sugar lycasin 430
Stabilizer citric acid 15 Flavorant tutti fruity flavor 5 Active
Ingredient Vitamin C 20.83 Fruit Juice Powder 30
EXAMPLE 5
A Sucrose-Free Soft Chewable Multivitamin Tablet Having a Vitamin C
Layer and Multi-Vitamins Layer
[0042] Corn syrup, maltitol, sorbitol solution, lactose and water
whose contents are shown in Table 5, were mixed, concentrated at
130.degree. C. and cooled to 90.degree. C. To the concentrated
solution were added a molten mixture of palm hydrogenated oil with
lecithin and glycerin fatty acid ester, which had been
preliminarily prepared and kneaded to a temperature of 70.degree.
C. Then, gelatin solution, strawberry flavor, FD & C Red No.
40, citric acid and an active ingredient of vitamin C whose
contents are shown in Table 5 were added to the above mixture, and
thoroughly kneaded, and then a kneaded material of vitamin
C-containing layer was prepared to have a material temperature of
40.degree. C. through tempering process. Subsequently, corn syrup,
maltitol, sorbitol solution, lactose and water were weighed in
accordance with the contents shown in Table 5, mixed, concentrated
at 130.degree. C. and cooled to 90.degree. C. analogously as in the
procedure of vitamin C layer. To the concentrated solution were
added a molten mixture of palm hydrogenated oil with lecithin and
glycerin fatty acid ester, which had been preliminarily prepared,
and kneaded to a temperature of 70.degree. C. Then, active
ingredients except for citric acid, strawberry flavor, FD&C Red
No. 40 and coated vitamin C were added to the above mixture in
accordance with the contents shown in Table 5, and thoroughly
kneaded, and then a kneaded material of multi-vitamins layer was
prepared to have a material temperature of 40.degree. C. through
tempering process. Thereafter, the said kneaded mixtures for
vitamin C layer and for multi-vitamins layer maintained at a
temperature of 40.degree. C. were subjected to an extruder with two
inlets, extruded, cooled, and cut to give a soft chewable
multilaminated tablet of 4 g which has vitamin C layer and
multi-vitamins layer was prepared, and packaged in a sealed
form.
5TABLE 5 The composition of a soft chewable multilaminated tablet
Vitamin C Vitamins Component (mg) (mg) Sugar corn syrup 750 750
maltitol 500 500 sorbitol solution 300 300 lactose 100 100 Fatty
Material palm hydrogenated oil 130 130 Emulsifier lecithin 2.5 2.5
glycerin fatty acid ester 5 5 Gum gelatin solution 6 6 Flavorant
strawberry flavor 5 -- tutti fruity flavor -- 6 Colorant FD&C
red No. 40 0.25 -- FD&C yellow No. 203 -- 0.2 Stabilizer citric
acid 12.5 -- Water 75 75 Active vitamin A -- 2 Ingredient vitamin
B.sub.1 -- 0.65 vitamin B.sub.2 -- 0.75 vitamin B.sub.6 -- 0.9 0.1%
vitamin B.sub.12 -- 2 vitamin D.sub.3 -- 1.15 tocopherol acetate --
5 folic acid -- 0.2 nicotinamide -- 5.4 calcium pantothenate -- 3
calcium phosphate -- 20 magnesium glycerophosphate -- 10 lecithin
-- 3.33 hippophae rhamnoides ext. 6 vitamin C (type SC) 20.83
--
EXAMPLE 6
A Soft Chewable Multilaminated Tablet Having a Vitamin Layer and
Mineral Layer
[0043] A multilaminated tablet was prepared in an analogous manner
as in Example 5, whose contents are shown in Table 6 below.
6TABLE 6 The composition of a soft chewable multilaminated tablet
Mineral Component Vitamin (mg) (mg) Sugar white sugar 500 500 corn
syrup 700 700 lactose 100 100 oligosaccharide 70 70 Fatty Material
hydrogenated vegetable 120 120 Emulsifier lecithin 2.5 2.5 Span 60
2.5 2.5 Fondant 250 250 Gum arabic gum (50%) 5 5 Stabilizer citric
acid 20 -- Flavorant grape flavor 7.5 7.5 Water 75 75 Active
Ingredient calcium carbonate -- 187.3 ferrous fumarate -- 7.6
magnesium carbonate -- 29.6 vitamin C 12.5 -- tocopherol acetate
7.5 --
COMPARATIVE EXAMPLE 1
A Conventional Soft Chewable Tablet Containing Multi-Vitamins
[0044] A soft chewable tablet whose components and contents are
shown in Table 1 was prepared by mixing all the active ingredients
in a simultaneous manner.
[0045] White sugar, corn syrup, lactose and water were mixed,
concentrated at 130.degree. C. and then cooled to 90.degree. C. To
the concentrated solution were added a molten mixture of
hydrogenated vegetable oil with glycerin fatty acid ester and
sorbitan monostearate, which had been preliminarily prepared and
kneaded to a temperature of 70.degree. C. Then, fondant, gelatin
solution, tutti fruity flavor and active ingredients were added
together with calcium pantothenate in an amount shown in Table 2 to
the above mixture, and thoroughly kneaded to a temperature of
40.degree. C. Thereafter, the kneaded mixture maintained at a
temperature of 40.degree. C. was subjected to extruding, rope
sizing and tabletting to give a soft chewable tablet of 4 g, and
packaged in a sealed form.
COMPARATIVE EXAMPLE 2
A Conventional Soft Chewable Tablet Containing Multi-Vitamins and
Citric Acid
[0046] A soft chewable tablet was prepared in an analogous manner
as in Comparative Example 1, with an exception of adding 25 mg of
citric acid.
COMPARATIVE EXAMPLE 3
A Conventional Soft Chewable Tablet Containing Vitamin and
Mineral
[0047] A soft chewable tablet was prepared analogously as in
Example 6, with an exception of mixing all the active ingredients
in a simultaneous manner.
COMPARATIVE EXAMPLE 4
A Conventional Soft Chewable Tablet Having a Core of Calcium
Pantothenate Containing Vitamin C and an Outer Shell of
Multi-Vitamins
[0048] A soft chewable tablet having a core was prepared in an
analogous manner as in Example 1, with an exception that a core
part contains vitamin C which is one of components of the outer
shell of Example 1.
COMPARATIVE EXAMPLE 5
A Conventional Soft Chewable Multilaminated Tablet Having a Core of
Vitamin C Containing Calcium Pantothenate and an Outer Shell of
Multi-Vitamins
[0049] A soft chewable tablet having a core was prepared in in an
analogous manner as in Example 5, with an exception that vitamin C
layer contains calcium pantothenate which is one of components of
multi-vitamins layer of Example 5.
[0050] Stability of Vitamin C and Calcium Pantothenate
[0051] The stabilities of vitamin C and calcium pantothenate in the
soft chewable tablets prepared in Examples 1 to 6 and Comparative
Examples 1 to 5 were examined over a period of 2 years. More than
20 soft chewable tablets were weighed and mean weight per tablet
was calculated. Tablets were finely cut and precisely took a weight
equivalent to two tablets (40 mg as vitamin C and 6 mg as calcium
pantothenate). To this was added 0.1N HCl, dissolved for 30 min,
and 0.1N HCl was added again, and dissolved while vortexing. Then,
ultrasonication was carried out for 30 min and 100 ml of test
solution was prepared by adding 0.1N HCl. On the other hand,
vitamin C 1,000 mg and calcium pantothenate 150 mg were dissolved
in water to give 50 ml of stock solution. To 2 ml of the stock
solution was added 0.1N HCl to obtain 100 ml of standard solution.
Thereafter, each of 10 .mu.l of test solution and standard solution
was injected to high performance liquid chromatography (HPLC) to
give peak area Rt and Rs values respectively, in accordance with
the analytical conditions described below and in Table 7. The
amounts of vitamin C and calcium pantothenate thus calculated were
disclosed in Table 8 below.
[0052] Column: Capcellpak C.sub.18 UG 120(46.times.250 mm, 5
.mu.m)
[0053] Column temperature: 40.degree. C.
[0054] Detector: UV spectrophotometer (measured at a wavelength of
210 nm)
[0055] Mobile phase:
[0056] A--70% (v/v) acetonitrile
[0057] B--5 mM hexane sodium sulfonate in 20 mM
phosphate/acetonitrile (91:9, v/v)
[0058] C--water
[0059] Calculation:
[0060] amount of vitamin C (C.sub.6H.sub.8O.sub.6) (mg) 1 amount of
vitamin C ( C 6 H 8 O 6 ) ( mg ) = amount of standard ( mg )
.times. Rt Rs .times. 1 25
[0061] amount of calcium pantothenate
(C.sub.18H.sub.32CaN.sub.2O.sub.10) (mg) 2 amount of calcium
pantothenate ( C 18 H 32 CaN 2 O 10 ) ( mg ) = amount of standard (
mg ) .times. Rt Rs .times. 1 25
7TABLE 7 Flow rate and concentration gradient of mobile phase in
HPLC Time (min) Flow Rate (ml/min) % A % B % C 0 0.8 -- 70 30 9 0.8
-- 70 30 9.5 0.8 -- 100 -- 24 0.8 -- 100 -- 24.5 0.8 8 92 -- 36 0.8
8 92 -- 36.5 0.8 -- 70 30
[0062]
8TABLE 8 Stabilities of vitamin C and calcium pantothenate in soft
chewable tablets (%) Examples Comparative Examples 1 2 3 4 5 6 1 2
3 4 5 Vitamin C initial 141 142 141 139 140 138 144 141 144 142 143
1 yr 105 130 130 127 129 132 107 127 82 113 128 2 yr 86 122 117 119
122 121 85 120 46 91 115 Calcium panto- thenate initial 143 140 141
139 142 -- 143 141 -- 143 140 1 yr 131 129 130 124 130 -- 94 61 --
103 91 2 yr 121 122 122 117 124 -- 47 24 -- 54 30
[0063] As clearly illustrated and demonstrated as aboves, the
present invention provides an improved soft chewable multivitamin
tablet in which vitamin C is separated from calcium pantothenate
and/or minerals such as iron, copper, zinc and mixtures thereof in
a core or multilaminate form and a process for preparing the same.
The soft chewable multivitamin tablet of the present invention
maintains its stability over a long-storage time in terms of the
content and potency of vitamins while overcoming the problems of
incompatibility, bad mouthfeel and palatability.
[0064] Although the preferred embodiments of the present invention
have been disclosed for illustrative purpose, those who are skilled
in the art will appreciate that various modifications, additions
and substitutions are possible, without departing from the spirit
or scope of the invention as it is set forth herein.
* * * * *