U.S. patent application number 09/160618 was filed with the patent office on 2001-11-01 for semi-moist oral delivery system.
Invention is credited to CHRISTENSEN, EDWIN H..
Application Number | 20010036464 09/160618 |
Document ID | / |
Family ID | 22577644 |
Filed Date | 2001-11-01 |
United States Patent
Application |
20010036464 |
Kind Code |
A1 |
CHRISTENSEN, EDWIN H. |
November 1, 2001 |
SEMI-MOIST ORAL DELIVERY SYSTEM
Abstract
These and other objects are attained by the subject invention
wherein there is provided a carrier or product formed of a matrix
having starch, sugar, fat, polyhydric alcohol and water in suitable
ratios such that there exists a water activity of 0.6-0.75. The
water activity of the product matrix is adjusted up or down so that
the availability of water in the finished product is not
detrimental to the included active ingredient, be it
pharmaceutical, nutraceutical, or a vitamin mineral complex.
Inventors: |
CHRISTENSEN, EDWIN H.;
(CORAL SPRINGS, FL) |
Correspondence
Address: |
WELSH & KATZ
120 SOUTH RIVERSIDE PLAZA
CHICAGO
IL
606063913
|
Family ID: |
22577644 |
Appl. No.: |
09/160618 |
Filed: |
September 24, 1998 |
Current U.S.
Class: |
424/400 |
Current CPC
Class: |
A61K 9/0056
20130101 |
Class at
Publication: |
424/400 |
International
Class: |
A61K 009/00 |
Claims
What is claimed is:
1. A carrier for the oral administration of an active ingredient to
mammals comprising: 10-50% starch, 0-40% fat or oil, 8-50%
polyhydric alcohol, 5-25% sugar 5-20% water, and 1-5% salt said
carrier having an A.sub.w of about 0.60 to 0.75.
2. The carrier of claim 1 wherein the water content is about
10%.
3. The carrier of claim 1 wherein the polyhydric alcohol content is
about 40%.
4. The carrier of claim 1 wherein the starch content is about
32%.
5. The carrier of claim 1 wherein the pregelatinized starch content
is about 15%
6. The carrier of claim 1 wherein the active ingredient is a
pharmaceutical.
7. The carrier of claim 1 wherein the active ingredient is a
nutraceutical.
8. The carrier of claim 1 wherein the active ingredient is a
vitamin and mineral mix.
9. The carrier of claim 1 where the A.sub.w is 0.65 and the active
ingredient is aspirin.
10. The carrier of claim 1 wherein the polyhydric alcohol is
sorbitol.
11. The carrier of claim 1 wherein the sugar content is about
15%.
12. A method of making a carrier for an active ingredient for use
in an oral administration of the active ingredient, comprising the
steps of: a) forming a matrix by mixing 10-50% starch, 0-40% fat or
oil, 10-50% polyhydric alcohol, 5-25% sugar, 5-20% water, and 1-5%
salt b) adjusting the relative amounts of polyhydric alcohol and
water to control the A.sub.w of said carrier; whereby the
controlled A.sub.w permits the moisture in the carrier to be at a
level not inimical to the active ingredient.
13. The method of claim 10 including adjusting the water content to
about 10%.
14. The method of claim 10 including adjusting the polyhydric
alcohol content to about 40%.
15. The method of claim 10 including adjusting the starch content
to about 32%.
16. The method of claim 10 including adjusting the sugar content to
about 15%.
17. The method of claim 10 including adjusting the pregelatinized
starch content is about 15%.
18. The method of claim 10 including the step of mixing in a
pharmaceutical.
19. The method of claim 10 including the step of mixing in a
nutraceutical.
20. The method of claim 10 including the step of mixing in a
vitamin and mineral mix.
21. The method of claim 10 including the step of adding
sorbitol.
22. The method of claim 10 including the step of controlling the
A.sub.w to be at about 0.60 to about 0.75.
23. The method of claim 10 including the step of adding aspirin as
the active ingredient and controlling the A.sub.w of said carrier
to about 0.65.
Description
FIELD OF THE INVENTION
[0001] This application is directed to a means for delivering
pharmaceuticals, nutraceuticals and the like to a mammal and more
specifically, the control of the water activity of a food product
matrix for use in the incorporation of a pharmaceutical,
nutraceutical or other bioactive compound into the matrix.
BACKGROUND OF THE INVENTION
[0002] Pharmaceutical and nutraceutical products intended for oral
administration are typically provided in tablet, capsule, pill,
lozenges and caplet form. These products are swallowed whole or
chewed in the mouth for delivery of the active ingredient into the
alimentary system of a body. Such oral delivery systems are
sometimes made chewable to ease drug administration in pediatric
and geriatric patients. Such concerns with ease of administration
may be amplified when dealing with pets and other animals.
[0003] As a result, several approaches have been utilized in
formulating oral delivery systems, including gums and candy bases.
The use of such delivery systems is limited by the reaction of the
active ingredient, whether it be pharmaceutical, nutraceutical or
other ingredients, to the existence of water in the system.
SUMMARY OF THE INVENTION
[0004] Therefore, an object of the subject invention is a method of
controlling water activity in an oral delivery system and the
product thereof.
[0005] A further object of the subject invention is a oral delivery
system for pharmaceuticals, nutraceuticals or other active
ingredient which matches the water activity of the carrier to the
included active ingredient.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0006] By the subject invention, a soft chewable oral delivery
system is provided. The dosage form may be in tablet form and may
contain one or more active ingredients. The active ingredients are
incorporated into the system which is described in further detail
below and which includes a starch component, a fat or oil, a sugar
component, a polyhydric alcohol, water and other minor ingredients.
Into this mixture is placed the active ingredient. After mixing and
extruding these ingredients, the extrudate is formed into the
appropriate shape. The relative proportions of the mixture are as
follows.
1 Starch 10-50% Fat or Oil 0-40% Sugar 5-25% Polyhydric Alcohol
10-50% Water 5-20% Salt (NaCl) 1-5% Active Ingredient 0.1-5%
[0007] Generally speaking, the starch component of the matrix
comprises 10 to 50 percent by weight of the matrix. More
particularly, the starch component of the matrix comprises 15 to 40
percent by weight of the matrix.
[0008] While starch for use in the matrix can be of any suitable
type, it is most preferred that at least part of the starch in the
matrix be a highly derivatized or pregelatinized starch. If a
highly derivatized starch is present in the matrix, it should be
present in an amount of about 1/2 percent by weight of the total
starch and the balance of the starch being non-derivatized. More
preferably, about 20-40 percent by weight of the total matrix and
about 45% of the total starch should be the derivatized starch. An
example of a preferred pregelatinized starch is A. E. Staley's
NU-COL 4227 or SOFT-SET.
[0009] Other amylaceous ingredients may be used in combination with
the derivatized starch or alone, provided the starch limits are not
exceeded. The amylaceous ingredients can be gelatinized or cooked
before or during the forming step to achieve the desired matrix
characteristics. If gelatinized starch is used, it may be possible
to prepare the product of the subject invention or perform the
method of the subject invention without heating or cooking of any
sort. However, if ungelatinized (ungelled) or uncooked starch is
used, the matrix must be cooked sufficiently to gel or cook the
starch to reach the desired content.
[0010] Starches that can serve as a base starch for derivatization
include regular corn, waxy corn, potato, tapioca, rice, etc. Such
types of derivatizing agents for the starch include but are not
limited to ethylene oxide, propylene oxide, acetic anhydride, and
succinic anhydride, and other food approved esters or ethers,
introducing such chemicals alone or in combination with one
another. Prior crosslinking of the starch may or may not be
necessary based on the pH of the system and the temperature used to
form the product.
[0011] By "amylaceous ingredients" is meant those food-stuffs
containing a preponderance of starch and/or starch-like material.
Examples of amylaceous ingredients are cereal grains and meals or
flours obtained upon grinding cereal grains such as corn, oats,
wheat, milo, barley, rice, and the various milling by-products of
these cereal grains such as wheat feed flour, wheat middlings,
mixed feed, wheat shorts, wheat red dog, oat groats, hominy feed,
and other such material. Also included as sources of amylaceous
ingredients are the tuberous food stuffs such as potatoes, tapioca,
and the like.
[0012] Another component of the matrix is a fat component such as
fat or oil of animal or vegetable origin. Typical animal fats or
oils are fish oil, chicken fat, tallow, choice white grease, prime
steam lard and mixtures thereof. Other animal fats are also
suitable for use in the matrix. Vegetable fats or oils are derived
from corn, soy, cottonseed, peanut, flax, rapeseed, sunflower,
other oil bearing vegetable seeds, and mixtures thereof.
Additionally, a mixture of animal or vegetable oils or fats is
suitable for use in the matrix. The fat component of the matrix is
about 0 to about 40% by weight of the matrix. More specifically,
the fat component of the matrix is about 20 percent by weight of
the matrix.
[0013] The polyhydric alcohol component of the matrix can be
selected from glycerol, sorbitol, propylene glycol, 1.3-butanediol,
and mixtures thereof with each other and other polyhydric alcohols.
Generally the polyhydric alcohol comprises about 10 to about 50
percent by weight of the matrix. More specifically, the polyhydric
alcohol comprises about 20 to about 40 percent by weight of the
matrix.
[0014] The sugar component can be employed in a dry or crystalline
condition or can be an aqueous syrup having a sugar concentration
of from 50 to about 95, preferably from 70 to about 80, weight
percent. The sugar used can be lactose, sucrose, fructose, glucose,
or maltose, depending on the particular application and price or
availability of a particular sugar. Examples of various well
established sources of these sugars are, corn syrup solids, malt
syrup, hydrolyzed corn starch, hydrol (syrup from glucose
manufacturing operations), raw and refined cane and beet sugars,
etc.
[0015] Water must be present in the matrix at least about 5 percent
by weight of the matrix. More specifically, water is present in the
matrix about 5 percent to about 20 percent by weight of the matrix.
The matrix thus formed usually has a water activity of 0.60 to
0.75.
[0016] While water must be at least 5 percent by weight of the
matrix, when the matrix is used in a food product, the moisture of
the food product must be adjusted. Generally the moisture content
of the matrix is such to give a moisture content of 5-15 percent to
the final soft dry food product. More preferred is a moisture
content of 5 percent to 14 percent. Most preferred is a moisture
content of 8 percent to 13 percent. The desired moisture content
may be achieved in any suitable fashion. Normal processing may
produce the moisture content desired. A standard drying step is
optional and may be used if necessary.
[0017] The active ingredient may be any drug, nutrition agent, or
the like which can be orally administered. Exemplary of such active
ingredients are the flowing: nutraceuticals, such as chromium
picolinate, potassium gluconate and methionine amino acid;
prescription drugs, such as ivermectin, fenbendazole, piperazine,
magnesium hydroxide, stranozole, furosemide, penicillin,
amoxicillin, prednisolone, methylprednisolone, acepromazine; and,
other pharmaceutical products, such as aspirin, prozac, zantac, and
benedryl. Minor amounts of flavorants, colorants, glycerin, flavor
enhancers, sweeteners, emulsifiers, antibitterness agents, taste
masking agents, stabilizers, preservatives, or combinations thereof
may be added.
[0018] To form the matrix, the starch system, fat, polyhydric
alcohol, corn syrup and water are mixed with a screw extruder,
permitting addition of ingredients and variable heating at
different points along the barrel. Other mixing apparatus, such as
a sigma mixer, swept wall heat exchanger or the like may be used.
If a coloration is desired in the final product, cooked or
pregelled starches are used to form the matrix. The use of these
starches avoids high cooking temperatures which would destroy the
desire coloration and/or active ingredient. If coloration active
temperature sensitivity is not a problem, it is possible to use an
uncooked or ungelatinized starch to form the matrix and cook or gel
the starch as the process is carried out. The incorporation of a
derivatized starch in the product more clearly guarantees the
softness of the product for a longer period of time. Softness is
also provided by the fats and oils. In this fashion a suitable
matrix is provided for use with a wide variety of active
ingredients.
[0019] Having fully described the invention, the following examples
are presented to illustrate the invention without limitation
thereof. In these examples all parts percentages are by weight
unless otherwise specified.
EXAMPLE 1
Carrier
[0020]
2 INGREDIENT PARTS Regular Corn Starch (Purefood GMI) 17.9 Pregel
Starch (SOFT SET) 15.0 Corn Syrup (Star Dri Corn Syrup Solids) 15.0
Corn Oil 20.0 Sorbitol 20.0 Active 0.1 H.sub.2O 10.0 Salt 2.0 TOTAL
100.0
[0021] The above ingredients are mixed at temperatures of about
125.degree. F., extruded and cut into a suitable tablet size. This
product has an oily, bubbly appearance suggesting cutting back on
the oil content. Temperature was also adjusted during each of the
following examples to eliminate puffing of the product as it exits
the extruder.
EXAMPLE 2
Guaifenesin
[0022]
3 INGREDIENT PARTS Regular Corn Starch (Purefood GMI) 17.9 Pregel
Starch (SOFT SET) 15.0 Corn Syrup (Star Dri Corn Syrup Solids) 15.0
Sorbitol 39.3 H.sub.2O 10.0 Salt 2.0 Guaifenesin* 0.8 TOTAL 100.0
*Available from Arrow Chemical Co., N.J.
EXAMPLE 3
Vitamins
[0023]
4 INGREDIENT PARTS Regular Corn Starch (Purefood GMI) 17.9 Pregel
Starch (SOFT SET) 15.0 Corn Syrup (Star Dri Corn Syrup Solids) 15.0
Sorbitol 35.1 H.sub.2O 10.0 Salt 2.0 Vitamin and Mineral Mix* 5.0
TOTAL 100.0 *Commercially available mixture available from Archer
Daniels Midland.
EXAMPLE 4
Flax
[0024]
5 INGREDIENT PARTS Regular Corn Starch (Purefood GMI) 17.9 Pregel
Starch (SOFT SET) 15.0 Corn Syrup (Star Dri Corn Syrup Solids) 15.0
Sorbitol 35.1 H.sub.2O 10.0 Salt 2.0 Flax* 5.0 TOTAL 100.0
*Available from Enreco Flax.
EXAMPLE 5
Acetaminophen
[0025]
6 INGREDIENT PARTS Regular Corn Starch (Purefood GMI) 17.9 Pregel
Starch (SOFT SET) 15.0 Corn Syrup (Star Dri Corn Syrup Solids) 15.0
Sorbitol 39.1 H.sub.2O 10.0 Salt 2.0 Acetaminophen* 0.8 Red
Coloring #40 0.1 Flavoring (Cherry) 0.1 TOTAL 100.0 *Available from
Mallincrodt as Compap
EXAMPLE 6
Carrier
[0026]
7 INGREDIENT PARTS Regular Corn Starch (Purefood GMI) 17.9 Pregel
Starch (SOFT SET) 15.0 Corn Syrup (Star Dri Corn Syrup Solids) 15.0
Sorbitol 40.1 H.sub.2O 10.0 Salt 2.0 TOTAL 100.0
[0027]
8TABLE 1 Example Active Oil/Sugar A.sub.W Extrusion Temp. 1 Premix
Corn Oil/Sorbitol N/A 125 2 Guaifenesin 100% Sorbitol 0.656 115 3
Vitamin Mix 100% Sorbitol 0.651 115 4 Flax 100% Sorbitol 0.673 115
5 Acetaminophen 100% Sorbitol 0.666 115 6 Premix 100% Sorbitol 0.61
115
[0028] By the above examples and Table 1 it is apparent that an
oral delivery system for the administration for pharmaceuticals,
nutraceuticals, vitamins and minerals and other active ingredients
may be provided in a chewable form by the subject invention. If the
active ingredient is water sensitive such as aspirin, then the
amount of polyhydric alcohol is increased, the water activity is
depressed to about 0.65 and the stability and texture of the
resultant product is maintained. If the active ingredient requires
or can tolerate the presence of free water for its activity, such
as in the case of Guaifenesin, the amount of polyhydric alcohol may
be decreased, while maintaining the level of such polyhydric
alcohol such that a soft texture of the resulting tablet is
maintained. In the case of Guaifenesin, then an A.sub.w of 0.70 may
be utilized and a softer, more chewable texture achieved. An
effective oral delivery system in which the texture and stability
of the product and activity of the active ingredient is
controllable, is the result.
[0029] While the invention has been described with reference to a
preferred embodiment, it will be understood by those skilled in the
art that various changes may be made and equivalents may be
substituted for elements thereof without departing from the scope
of the invention. In addition, many modifications may be made to
adapt a particular situation or material to the teachings of the
invention without departing from the essential scope thereof.
Therefore, it is intended that the invention not be limited to the
particular embodiment disclosed as the best mode contemplated for
carrying out this invention, but that the invention will include
all embodiments and equivalents falling within the scope of the
appended claims.
[0030] Various features of the invention are set forth in the
following claims.
* * * * *