U.S. patent number 3,608,083 [Application Number 04/734,540] was granted by the patent office on 1971-09-21 for vitamin e powder.
This patent grant is currently assigned to Hoffmann La Roche Inc.. Invention is credited to Raymond Howard Bunnell, Marco Alfred Cannalonga.
United States Patent |
3,608,083 |
Bunnell , et al. |
September 21, 1971 |
**Please see images for:
( Certificate of Correction ) ** |
VITAMIN E POWDER
Abstract
High potency vitamin E powders, suitable for use in tablets and
capsules are produced by spray drying an emulsion of a vitamin E
active compound and a gelatin hydrolysate having very low
Bloom.
Inventors: |
Bunnell; Raymond Howard
(Branchville, NJ), Cannalonga; Marco Alfred (Fort Lee,
NJ) |
Assignee: |
Hoffmann La Roche Inc. (Nutley,
NJ)
|
Family
ID: |
24952104 |
Appl.
No.: |
04/734,540 |
Filed: |
June 5, 1968 |
Current U.S.
Class: |
514/458;
514/774 |
Current CPC
Class: |
A61K
47/42 (20130101) |
Current International
Class: |
A61K
47/42 (20060101); A61k 015/10 () |
Field of
Search: |
;424/284,360
;167/81E,344 ;260/117,999 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Friedman; Stanley J.
Assistant Examiner: Drezin; Norman A.
Claims
What is claimed is:
1. A powder comprising from about 40 percent to about 60 percent by
weight of a vitamin E active compound and from about 60 percent to
about 40 percent by weight of a gelatin hydrolysate, said
hydrolysate having a 0 Bloom and a molecular weight of from about
9,000 to about 11,000.
2. The powder of claim 1 wherein the amount of the vitamin E active
compound present is 50 percent by weight.
3. The powder of claim 1 wherein the vitamin E active compound is
dl-.alpha.-tocopheryl acetate.
4. The powder of claim 1 containing from about 0.5 percent to about
0.9 percent of an antimicrobial preservative.
Description
SUMMARY OF THE INVENTION
This invention relates to vitamin E powders with good tabletting
characteristics suitable for incorporation into multivitamin
tablets and capsules and high potency vitamin E tablets. The
powders are composed of a vitamin E active compound, preferably
dl-.alpha.-tocopheryl acetate, and a gelatin hydrolysate having a
molecular weight of from about 9,000 to about 11,000 and a 0
Bloom.
BACKGROUND OF THE INVENTION
Vitamin E comprises a group of natural substances known as
tocopherols. They are fat-soluble, closely related chemical
compounds found in vegetable oils such as wheat germ oil, rice oil,
soybean oil and the like. .alpha.-Tocopherol has the greatest
biological activity while its isomers, beta, gamma, delta, epsilon,
zeta and eta tocopherols have vitamin E activity to a lesser
extent. The tocopherols and their esters such as tocopheryl
acetate, tocopheryl palmitate, tocopheryl succinate and the like
are normally water-insoluble and oily, waxy or low melting, which
properties make them unsuitable for certain pharmaceutical
applications, particularly, those in which a powder is required,
e.g., vitamin tablets and capsules.
DETAILED DESCRIPTION OF THE INVENTION
According to this invention, a powder containing from about 40
percent to about 60 percent by weight of vitamin E is provided.
This powder contains besides the vitamin E component, a gelatin
hydrolysate of very low Bloom. The amount of hydrolyzed gelatin in
the powder generally varies from about 60 percent to about 40
percent by weight. The gelatin hydrolysate suitable for use in this
invention has no Bloom or jelly strength, since it does not gel
under the conditions of the conventional gelatin test. It also has
a molecular weight of from about 9,000 to about 11,000. The jelly
strength of gelatin or gelatin hydrolysate is determined with a
62/3 percent solution. The solution is cooled down until gelation
occurs and then the strength of the gel is measured in grams. This
strength is called the Bloom or jelly strength. Thus, the
hydrolyzed gelatins useful in this invention have 0 Bloom since no
gelation occurs. When the concentration of the test solution is
doubled to about 121/2 percent then gelation takes place forming a
gel with a jelly strength of about 20 to 30 grams. A gelatin
hydrolysate which is representative of those suitable for use in
this invention is marketed under the name "Byco" soluble protein
Type E by D. Young and Company of America Ltd., New York, N.Y.
While this "Byco" soluble protein Type E is representative of the
hydrolyzed gelatins useful in this invention, the invention is not
limited to this particular gelatin hydrolysate since other
hydrolyzed gelatins with a very low Bloom and a molecular weight of
about 9,000 to about 11,000 are also suitable. The very low Bloom
hydrolyzed gelatins are suitable for use in this invention since
they are relatively stable to heat and can be kept warm for as long
as 8 hours without any off-odor developing. This relative heat
stability is important since it permits the use of this material in
granulation and tabletting procedures without odor problems. This
is in contrast to other hydrolyzed gelatins which develop
unpleasant off-odors when used in granulation and tabletting
operations. Furthermore, the low Bloom hydrolyzed gelatins have
good tabletting characteristics and compositions containing these
gelatins are readily granulated and/or compressed.
The hydrolyzed gelatins are made by a controlled hydrolysis of
edible gelatin which results in materials with the required Bloom
and molecular weight.
The vitamin E active compounds suitable for use in this invention
are any of the tocopherols, however, in order to insure the desired
amount of vitamin E activity in the powder on a weight basis, it is
preferred to use tocopheryl esters. Suitable esters are the
acetate, palmitate, succinate and the like. The preferred ester
used according to this invention is dl-.alpha.-tocopheryl acetate.
Sufficient tocopheryl acetate is utilized to insure that the
spray-dried powder contains from about 40 percent to about 60
percent by weight of vitamin E, i.e., the amount of vitamin E
activity present in the powder is that which would be present if
the vitamin E activity is present as pure vitamin E.
The vitamin-E-containing powders of this invention can contain a
flow agent to improve flow, increase bulk density and remove
electrostatic charges. The amount of flow agent present is
generally from about 1 percent to about 3percent by weight. The
flow agent is added to the powders prior to their use in tabletting
and encapsulating procedures. Suitable flow agents are, for
example, bulky silicic acid products such as Syloid 65, silicic
acid-Mallinckrodt Special Bulky, Santocel FRC, XP-50 (Huber),
Zeothix 90, and Cabosil M7.
The vitamin E powders of this invention are formed by emulsifying
the vitamin E compound and the gelatin hydrolysate and then spray
drying the emulsion. The conditions of the spray drying are not
critical just so long as the temperatures utilized are not so hot
that the vitamin E or gelatin hydrolysate is decomposed. Thus,
inlet temperatures of about 350.degree. F. to about 400.degree. F.
and outlet temperatures of about 190.degree. F. to about
220.degree. F. are suitable.
Since gelatin hydrolysate solutions readily support microbiological
growth, it is preferred to add preservatives to protect the
emulsion during preparation and holding prior to spray drying. The
preservatives are added to the water used to prepare the gelatin
solution so that a level of about 0.4 percent to about 0.6 percent,
preferably about 0.5 percent, of, for example, sodium benzoate and
about 0.15 percent to about 0.25 percent, preferably about 0.2
percent, of, for example, sorbic acid, result in a final 45 percent
by weight hydrolyzed gelatin solution. This provides a level of
about 0.20 percent-0.24 percent, preferably about 0.22 percent, of,
for example, sodium benzoate and about 0.08 percent to about 0.10
percent, preferably about 0.09percent, of, for example, sorbic acid
in the final emulsion and about 0.4 percent to about 0.6 percent,
preferably about 0.5 percent, of, for example, sodium benzoate and
about 0.15 percent to about 0.25 percent, preferably about 0.2
percent, of, for example, sorbic acid in the spray-dried
powder.
The moisture content of the spray-dried material is about 1 percent
to about 6 percent, usually about 3 percent. The powders produced
according to this invention are cold water soluble materials and
pick up some atmospheric moisture, however, they have very little
tendency to cake, for example, the product does not cake until
stored at 79 percent humidity for from 9 to 16 days, and the cake
thus formed is easily broken.
The powders according to this invention are white, have a particle
size range of from about 20 to 40 microns, of which at least about
90 percent pass through a 20-mesh screen. The bulk density of the
powders is from about 15 to about 22 lb./cu. ft. As used herein,
"20 -mesh" refers to a screen with 20 meshes per linear inch.
The following examples illustrate the preparation of the powders of
this invention.
Example 1
5 grams of sodium benzoate and 2 grams of sorbic acid are dissolved
in 550 grams of distilled water and heated to 60.degree.-70.degree.
C. 450 grams of gelatin hydrolysate ("Byco" soluble protein Type E)
are added and dissolved with constant agitation. 550 grams
dl,.alpha.-tocopheryl acetate are emulsified in the hydrolyzed
gelatin solution with a Homo-rod Mixer. The emulsion is diluted
with water, about 650 grams, to about 45 percent solids to give a
proper spray viscosity. The material is spray dried in a laboratory
model Bowen Spray Dryer using a rotating disc at an inlet
temperature of about 375.degree. F. and an outlet temperature of
about 210.degree. F. The resulting white powder is then blended
with a flow agent, e.g., Cabosil M7 (finely divided silica). The
product, prior to the addition of the flow agent, contains 50
percent by weight of vitamin E, 3 percent water, 0.5 percent sodium
benzoate and 0.2 percent sorbic acid with the remainder being
hydrolyzed gelatin.
Example 2
A 200-gallon jacketed Pfaudler kettle is charged with 50 gallons of
distilled water, 1.75 kg. of sodium benzoate and 0.70 kg. of sorbic
acid and heated to 65.degree. to 70.degree. C. 153 kg. of gelatin
hydrolysate ("Byco" soluble protein Type E) are slowly added with
constant agitation. 30 kg. of warm (35.degree.-40.degree. C.)
dl-.alpha.-tocopheryl acetate are slowly added to 50 kg. of the
hydrolyzed gelatin solution at 50.degree. -60.degree. C. and with
stirring, using a Homo-rod Mixer, until the emulsification is
complete. Sufficient distilled water is then added to provide a
proper spraying viscosity, e.g., about 45 percent solids.
The emulsion is then spray dried using either a 71/2-foot Nichols
Spray Dryer or a Bowen 71/2-foot Spray Dryer with an inlet
temperature of about 300.degree. F. and an outlet temperature of
about 200.degree. F. The resulting product is white, has particles
of from about 20 to about 30 microns, a bulk density of about 18.5
lb./cu. ft. and a moisture content of about 1 percent.
The product is blended with about 3 percent by weight Mallinckrodt
bulky silicic acid, prior to use in a tabletting operation.
Example 3
The powder formed in example 1 is used as an ingredient in a
multivitamin tablet in the following formulation:
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Parts by Weight
__________________________________________________________________________
Riboflavin 2.75 Pyridoxin HC1 1.10 Niacinamide 21.00 Ascorbic Acid
77.00 Vitamin E--50%--hydrolyzed gelatin (Product of example 1)
42.00 Pregelatinized starch binder (Amigel Boll) 16.00 Tricalcium
Phosphate 94.70 Dry vitamin A acetate, 500,000 units/g. 12.50
d-calcium pantothenate 1.50 Thiamine mononitrate 2.20 Vitamin
B.sub.12 --0.1% in gelatin 1.20 Calcium stearate 1.25 Silica
(Cabosil M7) 1.20 Dry vitamin D.sub.2 850,000 units/g. 0.60 Tablet
Weight (mg.) 275
__________________________________________________________________________
The riboflavin, pyridoxin, niacinamide, ascorbic acid, vitamin E,
Amijel and tricalcium phosphate were passed through a Fitzpatrick
mill equipped with a No. 1 screen, then granulated with water. The
granules were dried overnight at 115.degree. F. and then passed
through a Fitzpatrick mill, equipped with a No. 1-B screen
operating at medium speed, with knives forward.
The granulation was then admixed with the remaining ingredients
listed in the preceding formulation. Thereafter, the mixture was
compressed into tablets using a 15/32 inches flat faced
beveled-edge punch and the tablets, weighing between 240 and 360
mg., were sealed and sugar coated by sealing with shellac,
subcoating with syrup and dusting powder, coloring and smoothing
with syrup, and waxing and polishing.
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