U.S. patent application number 09/564289 was filed with the patent office on 2002-01-10 for discoloration-resistant vitamin composition.
Invention is credited to Oppenheim, Richard Charles, Truong, Hung Cam.
Application Number | 20020004069 09/564289 |
Document ID | / |
Family ID | 3804502 |
Filed Date | 2002-01-10 |
United States Patent
Application |
20020004069 |
Kind Code |
A1 |
Oppenheim, Richard Charles ;
et al. |
January 10, 2002 |
Discoloration-resistant vitamin composition
Abstract
The invention disclosed herein includes a vitamin composition
encapsulated in a soft or hard shell capsule, said vitamin
composition comprising water soluble vitamin particles suspended in
a fill liquid, wherein said water soluble vitamin particles are
coated with a material that is substantially insoluble in the fill
liquid and the shell of the capsule, but soluble in the
gastrointestinal tract of a mammal, and the coated water soluble
vitamin particles are of a size that are suitable for encapsulating
as a suspension in said capsule. The invention also includes a
process for manufacturing the same. Vitamin containing capsules
according to this invention are discoloration-resistant.
Inventors: |
Oppenheim, Richard Charles;
(Kew, AU) ; Truong, Hung Cam; (Chadstone,
AU) |
Correspondence
Address: |
Andrew G Rozycki
Cardinal Health Inc
7000 Cardinal Place
Dublin
OH
43017
US
|
Family ID: |
3804502 |
Appl. No.: |
09/564289 |
Filed: |
May 4, 2000 |
Current U.S.
Class: |
424/456 |
Current CPC
Class: |
A61K 9/1617 20130101;
A61K 9/4858 20130101; A61K 9/5015 20130101 |
Class at
Publication: |
424/456 |
International
Class: |
A61K 009/64 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 6, 1997 |
AU |
PP 0222 |
Claims
1. A vitamin composition encapsulated in a soft or hard shell
capsule, said vitamin composition comprising water soluble vitamin
particles suspended in a fill liquid, wherein; said water soluble
vitamin particles are coated with a material that is substantially
insoluble in said fill liquid and the shell of said capsule, but
soluble in the gastrointestinal tract of a mammal, and the coated
water soluble vitamin particles are of a size that are suitable for
encapsulating as a suspension in said capsule.
2. A vitamin composition according to claim 1 wherein the capsule
is a soft gelatin capsule.
3. A vitamin composition according to claim 1 or 2 wherein the
water soluble vitamin is selected from Thiamine, Riboflavin,
Nicotinic Acid, Pantothenic Acid, Pyridoxine, Biotin, Folic Acid,
Cyanocobalamin, Lipoic Acid and Ascorbic Acid.
4. A vitamin composition according to any one of the preceding
claims wherein the water soluble vitamin is Ascorbic Acid.
5. A vitamin composition according to any one of the preceding
claims wherein the fill liquid is hydrophobic.
6. A vitamin composition according to any one of the preceding
claims wherein the fill liquid is a vegetable oil, vegetable oil
derivative or a medium chain triglyceride or mixtures thereof.
7. A vitamin composition according to any one of the preceding
claims wherein the fill liquid is selected from Almond Oil; Arachis
Oil; Borage Oil; Canola Oil; Evening Primrose Oil; Fractionated
Coconut Oil; Lecithin; Linseed Oil; Maize Oil; Olive Oil; Rapeseed
Oil; Rice Bran Oil; Safflower Oil; Soya Bean Oil; Spearmint Oil;
Sunflower Oil or Wheatgerm Oil.
8. A vitamin composition according to any one of the preceding
claims wherein the coating material is hydrophilic.
9. A vitamin composition according to any one of the preceding
claims wherein the coating material is selected from a glycol, a
polyglycol or a polyglycol derivative having a molecular weight of
from 1000-8000.
10. An encapsulated vitamin composition according to claim 8 or 9
wherein the coating material is a lower alkoxy glycol, a lower
alkoxy polyglycol, a polyalkoxy or a polyoxy derivative.
11. A vitamin composition according to any one of claims 8 to 10
wherein the coating material is a polyethoxy glycol.
12. A vitamin composition according to any one of claims 1 to 4
wherein the fill liquid is hydrophilic.
13. A vitamin composition according to claim 12 wherein the fill
liquid is selected from a polyethylene glycol having a molecular
weight of from 300 to 8,000 or a mixture of a polyethylene glycol
with other polyols.
14. A vitamin composition according to claim 12 and 13 wherein the
fill liquid is Macrogol 400 or a mixture of Macrogol 400 and
propylene glycol and/or glycerol.
15. A vitamin composition according to any one of claims 12 to 14
wherein the coating material is a vegetable oil derivative, fatty
acid, a fatty acid derivative or a fatty oil.
16. A vitamin composition according to claim 14 wherein the coating
material is a hydrogenated vegetable oil.
17. A vitamin composition according to any one of the preceding
claims further including a suspending/dispersing agent.
18. A vitamin composition according to claim 17 wherein the
suspending dispersing agent is selected from fatty acids, lecithins
and wax mixtures or mixtures thereof if the fill liquid is
hydrophobic, and a high molecular weight polyethylene glycols or a
high molecular weight polyoxyethylene if the fill liquid is
hydrophilic.
19. A vitamin composition according to claim 18 wherein the high
molecular weight polyethylene glycol is Macrogol 8000.
20. A vitamin composition according to any one of the preceding
claims wherein the coated water soluble vitamin particle size is
less than 300 .mu.m.
21. A vitamin composition according to claim 20 wherein the coated
water soluble vitamin particles are a coated Ascorbic Acid particle
of less than 180 .mu.m.
22. A vitamin composition according to any one of the preceding
claims wherein the coating material comprises at least 10% by
weight of the coated vitamin particle.
23. A vitamin composition according to claim 22 wherein the coating
material comprises from 10% to 50% by weight of the coated vitamin
particle.
24. A vitamin composition according to claim 22 or 23 wherein the
coating material comprises approximately 30% by weight of the
coated vitamin particle.
25. A vitamin composition according to claim 2 wherein the shell of
the soft gelatin capsule comprises a mixture of gelatin, a suitable
polyol and water.
26. A vitamin composition according to claim 25 wherein the polyol
is glycerol.
27. A vitamin composition according to any one of the preceding
claims wherein the shell of the capsule is either opaque or clear
coloured in a citrus or light colour.
28. A vitamin composition according to any one of the preceding
claims wherein the capsule contains from 10 mg to 1000 mg of active
vitamin material.
29. A process for manufacturing a capsule containing a coated
vitamin composition including the steps of: (i) providing water
soluble vitamin particles which have been coated with a material
that is insoluble in a fill liquid and the shell of a soft or hard
shell capsule, but soluble in the gastrointestinal tract of a
mammal, wherein the coated water soluble vitamin particles are of a
size that are suitable for encapsulating as a suspension; (ii)
suspending the coated vitamin particles in a compatible fill
liquid; and (iii) encapsulating the vitamin composition in a soft
or hard shell capsule to produce a vitamin composition according to
any one of the preceding claims.
30. A process according to claim 29 wherein the compatible fill
liquid is selected from a hydrophobic fill liquid if the coating
material is hydrophilic, and a hydrophilic fill liquid if the
coating material is hydrophobic.
31. A vitamin composition according to claim 1 substantially as
hereinbefore described with reference to any one of the examples.
Description
[0001] This application relates to an encapsulated vitamin
composition, and is particularly applicable to a vitamin
composition encapsulated in a soft gelatin capsule.
[0002] Soft and hard shell capsules are widely used within the
pharmaceutical and health food industry and have gained an
acceptance as they present pharmaceutical and health products in a
form that is readily consumed and digested by a user. These
capsules are generally made up of a shell and an active filling
material. The shell is formed of readily digested materials, for
example a soft gelatin capsule may comprise a mixture of gelatin,
glycerol and water. Hard shell capsules generally comprise gelatin
and water. Generally soft and hard shell capsules are suitable for
encapsulating a wide range of pharmaceutical and health products in
the form of a suspension.
[0003] Water soluble vitamins such as the B group vitamins, and
Ascorbic Acid are generally presented in the form of a suspension
in edible oil when encapsulated in a soft gelatin or hard shell
capsule. Oils such as Soya Bean Oil are generally used. The
vitamins may be used on their own as the active ingredient, or in
combination with herbal materials such as Biofiavanoids, Rutin etc;
or with other vitamins. Ascorbic Acid for example, may be combined
with other vitamins such as B groups, Betacarotene, Vitamin D and
Vitamin E etc; or with minerals such as trace elements of iron,
calcium, magnesium and zinc etc. Soft gelatin capsules containing
vitamins such as Ascorbic Acid are used for a number of therapeutic
and complementary medicine purposes, for example as a component in
anti-oxidant therapy in conjunction with Betacarotene and Vitamin
E.
[0004] Ascorbic Acid has been formulated in a soft gelatin capsule
for some time. Generally, when such capsules are presented in the
market place they are prepared with opaque shell colouring.
Ascorbic Acid and other water-soluble vitamins, such as the B group
vitamins, however have a finite solubility in the shell and can
migrate from the filling material to the shell if not completely
insolubilised. Over time, the water soluble vitamin in the shell
may oxidise or may react with the shell causing the shell to
darken. The amount needed to cause this darkening can be quite
small. The darkening will not effect the overall assay of the
capsule, however it can become unsightly. For this reason,
generally dark, opaque shells are used to encapsulate Ascorbic Acid
and B group vitamin compositions to hide the darkening of the
shell. The darkening precludes the use of light colours such as
citrus colours for the shell, such as yellow, orange or lime
colouring.
[0005] Accordingly, it is an object of the present invention to
overcome or at least alleviate one or more of the difficulties
associated with the prior art.
[0006] As part of the development of this invention, it was
considered that if the water soluble vitamin particle such as an
Ascorbic Acid particle was coated with a material that did not
dissolve in both the fill liquid excipients, such as oil based
solutions or other encapsulatable liquid based systems, and the
shell of the soft or hard shell capsule, but was still able to
dissolve from the vitamin particle in the gastrointestinal tract,
then the disadvantages of discolouration of the shell may be
overcome. Ascorbic Acid particles that are available for use in
tablet form may be coated, but have a much larger particle size
than what would be suitable for use as a filling material for a
soft gelatin or hard shell capsule.
[0007] Accordingly, in a first aspect, the present invention
resides in a vitamin composition encapsulated in a soft or hard
shell capsule, said vitamin composition comprising water soluble
vitamin particles suspended in a fill liquid, wherein;
[0008] said water soluble vitamin particles are coated with a
material that is substantially insoluble in the fill liquid and the
shell of the capsule, but soluble in the gastrointestinal tract of
a mammal, and
[0009] the coated water soluble vitamin particles are of a size
that are suitable for encapsulating as a suspension in said
capsule.
[0010] Most preferably the capsule is a soft gelatin capsule
comprising gelatin, a suitable polyol and water. The suitable
polyol is preferably glycerol. Although soft gelatin capsules are
preferred, the advantages of the invention are applicable to other
soft shell capsules and hard shell capsules, and compositions
encapsulated in hard shell capsules also form part of the
invention.
[0011] Water soluble vitamins that have found to be suitable for
use in this invention are the B group vitamins namely Thiamine,
Riboflavin, Folic Acid, Biotin, Nicotinic Acid, Pantothenic Acid,
Pyridoxine, Cyanocobalamine and Lipoic Acid and Vitamin C, namely
Ascorbic Acid. The invention has been found to be particularly
applicable for use with Ascorbic Acid.
[0012] The fill liquids of the invention may be any liquid based
system that is encapsulatable in a soft or hard shell capsule. The
coating material may be either hydrophobic or hydrophilic in
nature. The selection of the fill liquid for encapsulation will
depend upon the nature of the coating material used. For example,
if the coating material is hydrophobic, a hydrophilic fill liquid,
such as Macrogol 400 will preferably be used. If the coating
material is hydrophilic, a hydrophobic fill liquid will preferably
be used, such as Soya Bean Oil. This will ensure that the coating
material will be insoluble in the fill liquid.
[0013] Preferred hydrophobic fill liquids include vegetable oil,
vegetable oil derivatives or medium chain triglycerides or mixtures
thereof. Suitable vegetable oils include Almond Oil; Arachis Oil;
Borage Oil; Canola Oil; Evening Primrose Oil; Fractionated Coconut
Oil; Lecithin; Linseed Oil; Maize Oil; Olive Oil; Rapeseed Oil;
Rice Bran Oil; Safflower Oil; Soya Bean Oil; Spearmint Oil;
Sunflower Oil or Wheatgerm Oil.
[0014] Preferred hydrophilic fill liquids include polyethylene
glycols having a molecular weight of from 300 to 8,000 or mixtures
of polyethylene glycol with other polyols. Most preferred
hydrophilic fill liquids include Macrogol 400 and mixtures of
Macrogol 400 and propylene glycol and/or glycerol.
[0015] The coating material may comprise any material having the
requisite properties of insolubility in the fill liquid and the
shell of the capsule, whilst being able to disassociate from the
particle in the gastrointestinal tract.
[0016] The selection of the fill liquid is determined by the
solubility of coating material in the fill liquid. Whereas this is
largely determined by the hydrophobic/hydrophilic nature of the
fill liquid, it has been found that some hydrophobic coating
materials remain insoluble in hydrophobic fill liquids. For
example, some hydrogenated vegetable oils remain insoluble in a
hydrophobic fill liquid such as Soya Bean Oil. Similarly some
hydrophilic coating materials will remain insoluble in polyethylene
glycol fill liquids.
[0017] Whereas it is preferred to select the fill liquid by its
hydrophobic/hydrophilic nature, the selection of the fill liquid is
determined by the solubility of the coating material in the fill
liquid.
[0018] Suitable hydrophilic coating materials include glycols and
polyglycols having a molecular weight of from 1000-8000. Preferred
hydrophilic coating materials include lower alkoxy glycols and
lower alkoxy polyglycols, for example, a most preferred material is
polyethoxy glycol.
[0019] Suitable hydrophobic coating materials include vegetable oil
derivatives, fatty acids, fatty acid derivatives including polyoxy
ethylene derivatives or fatty oils. Most preferred are hydrogenated
vegetable oils, for example derivatives based on Arachis, Coconut
or Soya Bean Oils.
[0020] The selection of an appropriate fill liquid is essential to
ensure that the coating material will remain insoluble within the
fill liquid and the shell of the capsule. For this reason it is
preferred that if the coating material is essentially hydrophilic
in nature, the fill liquid will be hydrophobic. If the coating
material is essentially hydrophobic in nature, the fill liquid will
preferably be hydrophilic.
[0021] In some circumstances, the coating material may contain a
mixture of materials, including a mix of hydrophilic and
hydrophobic materials. In such circumstances the selection of fill
liquid is determined by the overall nature of the coating material
and whether that coating material will remain insoluble in the fill
liquid. It is however anticipated that the coating material will be
essentially either hydrophilic or hydrophobic in nature.
[0022] The shell of some soft and hard shell capsules may be
considered to be slightly hydrophilic in nature. It has been found
that the preferred hydrophilic and hydrophobic coating materials of
the invention remain substantially insoluble against the shell of
the soft or hard shell capsule. It is only appropriate to use
coating materials that are substantially insoluble against the
shell of the capsule.
[0023] The coating material should be continuous surrounding the
vitamin particle to avoid leaching of the vitamin. Preferably, the
coating material comprises at least 10% w/w of the coated vitamin
particle. More preferably the coating material comprises between
10% w/w and up to 50% w/w of the coated particle and most
preferably about 30% w/w.
[0024] The coated vitamin particle size may be of any size that is
suitable for encapsulation as a suspension in a soft or hard shell
capsule. Preferably the particle size is 300 .mu.m or less however
larger particle sizes are also contemplated. Most preferably, the
particle size is 180 .mu.m or less. As the vitamin composition is
presented as a suspension, the particle size of the coated vitamin
particle should be appropriate for encapsulation as a suspension in
a soft or hard shell capsule.
[0025] The coated vitamin particle may be produced by first coating
the particles and then obtaining the correct particle size upper
limit by sieving out the bigger particles. The coating may also be
achieved by admixing the coating material and the vitamin, however
an inferior result is generally achieved unless a continuous
coating of the particle is achieved and aggregates of the particles
are removed.
[0026] The fill liquid may also include other suspending/dispersing
agents such as fatty acids, lecithins and wax mixtures if the fill
liquid is hydrophobic, or higher molecular weight dispersing agents
such as Macrogol 8000 if a hydrophilic fill liquid excipient is
used.
[0027] The soft or hard shell capsule may include any suitable
amount of vitamin particles in suspension, but generally will
include from 10 mg to 1000 mg of vitamin as an active ingredient.
The vitamin composition may include a mixture of coated vitamin
particles or a combination of coated particles and other coated or
uncoated active ingredients.
[0028] During the manufacturing process, it is most preferred that
the coated vitamin particle is not milled by a high shear process
prior to encapsulation in the soft or hard shell capsule. Milling
the coated particles by high shear processes may cause the coating
material to crack, which can lead to migration of the vitamin
material to the shell. Generally a continuous coating is maintained
if the coated particle is not milled by high shear processes prior
to encapsulation.
[0029] The present invention also resides in a process for
manufacturing a soft or hard shell capsule containing a coated
vitamin composition including the steps of:
[0030] (i) providing water soluble vitamin particles which have
been coated with a material that is insoluble in a fill liquid and
the shell of a soft or hard shell capsule, but soluble in the
gastrointestinal tract of a mammal, wherein the coated water
soluble vitamin particles are of a size that are suitable for
encapsulating as a suspension in the capsule;
[0031] (ii) suspending the coated vitamin particles in a compatible
fill liquid; and
[0032] (iii) encapsulating the vitamin composition in a soft or
hard shell capsule to produce the vitamin composition as
hereinbefore described.
[0033] It is a particular advantage of the present invention that
any darkening of the shell by the vitamin is avoided. Therefore
this avoids the need to utilise dark shell colours when
encapsulating the vitamin. Although conventional shell colours may
be used, the shell of the soft or hard shell capsule of the
invention may also be coloured to reflect citrus fruits, for
example colours such as yellow, orange and lime may be used. Other
light colours may also be used. The shell may also be clear or
clear coloured. Fruit flavours, odours, perfumes and other
additives may also be used as an additive to the shell material.
This is particularly advantageous when encapsulating Ascorbic
Acid.
[0034] The present invention will now be described with reference
to the following examples. It should be appreciated that these
examples are merely illustrative of the present invention and that
the present invention should not be considered to be limited
thereto.
EXAMPLE 1
[0035] Some pilot filling material consisting of a coated Ascorbic
Acid composition, Soya Bean Oil and a suspending/dispersing wax
mixture was encapsulated in a soft gelatin capsule. The soft
gelatin capsule shell comprised a mixture of gelatin, glycerol and
water. The particles were coated with a fat composition of either
10, 20 and 30% w/w. As a control, uncoated Ascorbic Acid was used
in a similar suspending solution and encapsulated in a similar soft
gelatin capsule. The capsules were placed within a sealed HDPE
bottle.
[0036] The following Table represents the results of shell
discolouration after six weeks stored at different
temperatures.
1 Discolouration 40.degree. C. 30.degree. C. 5.degree. C. Control
Significant Significant None 10% w/w Some Some, but less than at
40.degree. C. None 20% w/w Slight Slight, but less than at
40.degree. C. None 30% w/w None None None
[0037] The results show that with a 30% w/w there was no leaching
of the Ascorbic Acid to this shell material. Whereas there was some
slight discolouration at 20% w/w that discolouration was within
acceptable levels. There was some discolouration with the 10% w/w
coated particle which may indicate that the particle coating was
not continuous.
[0038] At 30.degree. C., the results were in the same order but to
a less extent than at 40.degree. C. At 5.degree. C. there was no
discolouration noticed in any of the capsules.
EXAMPLE 2
[0039] The stability trials for the Ascorbic Acid composition
described in Example 1 continued over a ten month period. Shell
darkening occurred in all lots however there was an appreciable
difference between the shell darkening in those compositions where
the Ascorbic Acid particle was coated. Those capsules that
contained particles of 30% w/w showed the least darkening.
[0040] The trial over the ten month period demonstrated that the
capsule containing uncoated (0%) particles are appreciably darker
than those capsules that contain coated Ascorbic Acid particles. As
anticipated those particles that have been subjected to 40.degree.
C. heat and 75% relative humidity show appreciably more darkening
than those capsules that have not been subjected to such heat,
however the capsules that contain coated particles show less
darkening even under those adverse temperature conditions.
Relatively little darkening occurred in those capsules that had
been coated with 10%, 20% and 30% w/w of coating material at
30.degree. C. while even less darkening occurred at 5.degree.
C.
[0041] Finally, it should be appreciated that many variations,
modifications and alterations may be made to the above described
composition without departing from the spirit or ambit of the
invention.
* * * * *