U.S. patent application number 11/296181 was filed with the patent office on 2007-06-07 for process for manufacturing chewable dosage forms for drug delivery and products thereof.
This patent application is currently assigned to Piedmont Pharmaceuticals, Inc.. Invention is credited to Michael Coffee, Roland Johnson, Neil E. Paulsen.
Application Number | 20070128251 11/296181 |
Document ID | / |
Family ID | 38119040 |
Filed Date | 2007-06-07 |
United States Patent
Application |
20070128251 |
Kind Code |
A1 |
Paulsen; Neil E. ; et
al. |
June 7, 2007 |
Process for manufacturing chewable dosage forms for drug delivery
and products thereof
Abstract
A palatable, soft chewable medication vehicle for delivery of a
pharmaceutically acceptable active ingredient, such as a drug, to
an animal or human subject. The soft chews contain only food grade
or better inactive ingredients, and preferably do not contain
ingredients of animal origin. Processes for manufacturing the soft
chews do not require the generation of heat during mixing of active
and inactive ingredients, provide stable concentrations of the
active ingredient, and produce chews of consistent weight and
texture.
Inventors: |
Paulsen; Neil E.; (Johns
Island, SC) ; Johnson; Roland; (Lexington, NC)
; Coffee; Michael; (Greensboro, NC) |
Correspondence
Address: |
FOLEY & LARDNER LLP
P.O. BOX 80278
SAN DIEGO
CA
92138-0278
US
|
Assignee: |
Piedmont Pharmaceuticals,
Inc.
|
Family ID: |
38119040 |
Appl. No.: |
11/296181 |
Filed: |
December 7, 2005 |
Current U.S.
Class: |
424/439 |
Current CPC
Class: |
A61K 9/2013 20130101;
A61K 9/2081 20130101; A61P 31/04 20180101; A61K 47/44 20130101;
A61K 9/5047 20130101; A61K 9/1617 20130101; A61K 9/1623 20130101;
A61K 9/2095 20130101; A61P 31/12 20180101; A61K 9/1641 20130101;
A61K 47/10 20130101; A61K 9/1652 20130101; A61K 9/0056 20130101;
A61K 9/1664 20130101; A61K 9/2018 20130101; A61K 9/2031 20130101;
A61K 9/2059 20130101; A61K 9/2068 20130101; A61P 25/04 20180101;
A61P 33/14 20180101; A61K 9/2077 20130101; A61P 31/10 20180101;
A61K 47/36 20130101; A61K 47/06 20130101; A61K 47/26 20130101; A61P
29/00 20180101; A61K 47/46 20130101 |
Class at
Publication: |
424/439 |
International
Class: |
A61K 47/00 20060101
A61K047/00 |
Claims
1. A process for manufacturing a soft chewable medication vehicle
for delivery of a pharmaceutically active ingredient, the method
comprising: (a) providing the active ingredient and dry inactive
ingredients of the medication vehicle to a mixing chamber of a
mixer, wherein: (i) the chamber is generally horizontally disposed
and has a space therein defined by walls to receive material to be
mixed; (ii) a rotatable mixing shaft extends longitudinally through
the chamber space; and, (iii) a drive apparatus is operably coupled
to the mixing shaft for rotating the shaft, (b) blending the dry
active and inactive ingredients in the mixing chamber by causing
the mixing shaft to be rotated to cast the ingredients in a pattern
away from and between the walls of the mixing chamber space until a
dry mixture is formed; (c) adding a softening agent to the dry
mixture and blending it therein to form a soft chewable mixture;
and, (d) forming the soft chewable mixture into individual masses,
wherein the masses are of consistent weight, wherein further no
heat is applied to the dry or blended chewable mixture during any
of the mixing or forming steps.
2. The process according to claim 1, further comprising the step of
preparing a trituration of the active ingredient with an excipient
before the active ingredient is added to the mixing vessel in step
(a).
3. The process according to claim 1, further comprising the step
(c)' of adding melted paraffin wax to the soft chewable mixture and
blending it therein.
4. The process according to claim 1 or claim 2, further comprising
the step (d)' of coating the active ingredient with a food grade
coating before the active ingredient is added to the mixing vessel
in step (a).
5. The process according to claim 1, further comprising step (e)
wherein the individual masses are placed into a pharmaceutically
acceptable container.
6. A medication vehicle comprising of a pharmaceutically acceptable
active ingredient in a soft chewable mass, wherein the medication
is produced according to the process of claim 1.
7. The medication vehicle according to claim 6, further comprising
inactive ingredients, wherein all of the inactive ingredients are
of food grade quality.
8. The medication vehicle according to claim 7, wherein the
inactive ingredients are irradiated or pasteurized.
9. The medication vehicle according to claim 6, further comprising
inactive ingredients, wherein none of the inactive ingredients are
of animal origin.
10. The medication vehicle according to claim 7, wherein the
inactive ingredients include flavorings of food grade quality.
11. The medication vehicle according to claim 9, wherein the
inactive ingredients include flavorings of non-animal origin.
12. The medication vehicle according to claim 11, wherein the
flavoring is a soy protein product.
13. The medication vehicle according to claim 12, wherein the
flavoring is an artificially bacon flavored soy protein
product.
14. The medication vehicle according to claim 6, further comprising
a lubricant, a humectant, and a bulking agent.
15. The medication vehicle according to claim 6, wherein the
pharmaceutically active ingredient is prepared in a trituration
with an excipient.
16. The medication vehicle according to claim 14, wherein the
softening agent comprises an oil.
17. The medication vehicle according to claim 14, wherein the
softening agent comprises wax.
18. The medication vehicle according to claim 6, wherein the
pharmaceutically active agent is coated.
19. The medication vehicle according to claim 6, further comprising
a preservative.
20. The medication vehicle according to claim 14, wherein the
softening agent comprises an oil and a wax, the humectant comprises
glycerin, and the lubricant comprises a stearate.
21. The medication according to claim 20, wherein the
pharmaceutically active ingredient is selected from the group of
ingredients consisting of anthelmetics, analgesics, antibiotics,
antivirals, anti-inflammatories, endo-parasiticides,
ecto-parasiticides and antifungals.
22. The medication according to claim 21, wherein the
pharmaceutically active ingredient is an anthelmetic.
23. The medication according to claim 22, having the ingredients of
Formula 1 and an active ingredient.
Description
FIELD OF THE INVENTION
[0001] The invention relates to the field of orally administrable
pharmaceutical dosage units; in particular, units in the form of an
edible mass, such as a chunk.
BACKGROUND OF THE INVENTION
[0002] Formulation of a drug into an edible medication, such as a
chewable tablet or confection, can increase patient acceptance of
the medication, especially animals, who tend to resist swallowing
hard tablets or capsules. Unfortunately, many drugs and other
active ingredients (collectively, "actives") have a strongly bitter
or otherwise unpalatable taste, making chewing them unpleasant.
[0003] Flavorings are commonly added to chewable medications to
enhance their palatability. For example, a veterinary medication
might include animal product-based flavorings such as uncooked
dried meat parts such as beef, pork, chicken, turkey, fish and
lamb; organ meats such as liver; meat meals, bone meals and ground
bone; and animal-derived food such as casein, milk (which may
include dry forms and lowered fat forms, such as dry skim milk),
yogurt, gelatin, cheese and egg (collectively, "animal origin
flavorings") may be utilized.
[0004] However, use of many animal origin flavorings (especially of
meat, poultry or seafood origin) risks exposure to infectious
agents, not only to the recipient of the drug, but also through
contamination of manufacturing equipment on which the flavored
dosage units are made. For this reason, manufacturing facilities
that prepare pharmaceutical products with animal origin flavorings
are often devoted exclusively to their preparation, at a
correspondingly greater cost than would be incurred if
manufacturing could be performed in a facility capable of
concurrently processing multiple products.
[0005] Texture is also an issue for chewable medications. One of
the most commonly used form for chewable dosage units is the
compressed tablet, whose ingredients (including the actives and
inactive ingredients such as binders) can make the tablet gritty or
otherwise unappealing, especially to animals. Thus, a preferred
alternative dosage form for use especially with animals is the
"soft chew," generally a meat-like mass or chunk also widely found
in consumable pet treats.
[0006] Soft chews are typically manufactured by blending and
extrusion. Pre-mixed ingredients are introduced into an extruder
barrel with a screw therein, then mixed, coagulated, expanded and
sheared into a blended mixture, followed by application of
additional heat if a harder texture is desired. Water introduced
into the mixture must generally be of pharmaceutical grade, as it
will be retained within the mixture. The blended mixture is then
formed into a desired shape on a die plate, then cut into
individual units.
[0007] The heat generated during the extrusion process can cause
deterioration in the stability (potency or integrity) of the active
in the mixture, causing the effective dose provided by each unit
formed to vary. Consistency of texture, shape and weights of the
chews from batch to batch of extruded material can also suffer.
[0008] There is a need, therefore, for a method of manufacture for
soft chewable medications in which the blending of actives into the
chew mixture is achieved without generation of heat. It is also
desirable that the chews be susceptible to manufacture without use
of costly, pharmaceutical grade water as an ingredient. There is
also a need in the art for a soft chew medication whose taste
appeals to animals without use of ingredients that may include
infectious agents or contaminants. Further, it is highly desirable
for the manufacturing means employed to produce chewable
medications to do so in a manner that ensures consistent chew
weights, texture and active dosages.
SUMMARY OF THE INVENTION
[0009] The invention provides a unique soft chew medication and
processes for its manufacture. The soft chews of the invention are
particularly palatable to pet animals. They contain inactive
ingredients of at least food grade quality, and most preferably do
not contain inactive ingredients of animal origin. As such, the
soft chews may be manufactured without concern about transmission
of infectious agents or contaminants, and without risk of
cross-contaminating other products produced in the same
manufacturing facility.
[0010] The manufacturing processes of the invention allow the soft
chews to be produced without application of heat to the ingredient
mixture. Stability of the actives is therefore preserved, and a
well-blended, soft texture is provided. Further, no water is used
as an ingredient of the chews, thereby avoiding the need for use of
costly pharmaceutical grade water, while reducing the opportunity
for microbial growth or loss of potency by the active.
[0011] To these ends, the soft chews of the invention are
manufactured using large capacity horizontal mixers which spins the
chew mixture into particulate form. The mixing action causes the
ingredients in the mixture to be cast away from the mixing vessel
walls, crisscrossing the vessel to provide a uniformly blended
mixture formed without application of heat. Because no cooling step
is required, the time to produce chews is shortened compared to
cooking extrusion methods.
[0012] The highly blended mixture produced is placed into molds to
form individual dosage units and allowed to set without application
of heat. Soft chews can be produced in any desired shape. Preferred
mixing and molding equipment utilized in the invention can provide
individual soft chews with consistently blended ingredients, stably
provided actives and consistent weights.
[0013] The soft chews of the invention are produced in palatable
form without the use of any non-food grade inactive ingredients
(or, preferably, any animal origin inactive ingredients). The
manufacturing processes may therefore be performed without risk of
potential cross-contamination of other equipment in the facility
with infectious agents or contaminants derived from sources such as
the animal-origin meat flavorings commonly used in chewable
medications for animals.
DETAILED DESCRIPTION OF THE INVENTION
A. Materials for use in Soft Chews of the Invention.
[0014] In general, soft chewable medications and treats include as
inactive ingredients matter such as binding agents, vitamins, and
colors to enhance the manufacturability, texture and appearance of
the product. Those of ordinary skill in the art will be familiar
with such inactive ingredients, which need not include water for
use in the invention.
[0015] For use in the invention, no inactive ingredients of the
soft chew should be of less than food grade quality and may be of
higher quality (e.g., USP or NF grade). In this context, "food
grade" refers to material that does not contain or impart chemicals
or agents hazardous to health. Thus, a food grade flavoring, if of
animal origin, will be one that has been prepared to substantially
reduce or eliminate the presence of infectious agents or
contaminants therein; e.g., by processes such as pasteurization,
pressurization or irradiation.
[0016] The latter process in particular can effectively eliminate
infectious agents such as E. coli O157:H7, Salmonella and
Campylobacter from a wide variety of food and animal-derived
substances, such as raw meat products, vegetables, grains and
fruits. Preferably, however, soft chews of the invention will not
contain any animal origin ingredients, and most preferably will not
contain any animal origin flavorings. All ingredients should be
pharmaceutically acceptable (e.g., food grade, USP or NF, as
appropriate).
[0017] Flavorings are preferably present in soft chews of the
invention that are at least food grade in quality, and most
preferably exclude animal origin flavorings. Preferred non-animal
origin flavorings are plant proteins, such as soy protein, to which
edible artificial food-like flavorings has been added (e.g.,
soy-derived bacon flavoring). Depending on the target animal, other
non-animal flavorings could include anise oil, carob, peanuts,
fruit flavors, sweeteners such as honey, sugar, maple syrup and
fructose, herbs such as parsley, celery leaves, peppermint,
spearmint, garlic, or combinations thereof.
[0018] A particularly preferred flavoring for use in the invention
is Provestar.TM. 356, made by ABF Ingredients, Inc. It is a light
tan, water-soluble powder that builds on the properties of yeast
extracts and reaction flavors to provide a pleasant smoky, cured
bacon flavor. Provesta 356 contains no animal derived
ingredients.
[0019] For administration to horses and other grazing animals, as
well as small animals such as rabbits, hamsters, gerbils, and
guinea pigs, grains and seeds are especially appealing additional
flavoring agents. The grains may be present in any form consistent
with the production of the chew including flour, bran, cereal,
fiber, whole grain and meal forms, including gluten meals, and may
be rolled, crimped, ground, dehydrated or milled. Minerals may also
be added as flavorings, such as salt and other spices. Preferably,
the grain utilized is dehydrated, milled or flaked. Vegetables such
as dehydrated carrots and seeds such as safflower seeds or milo
seeds are especially appealing to small animals and may be
included.
[0020] Further, agents which enhance the manufacturability and
texture of a soft chew may include softening agents, an anti-caking
agent or lubricant, and a humectant or wetting agent. Illustrative
examples of lubricants or anti-caking agents which may be used in
the invention include magnesium stearate, calcium stearate, solid
polyethylene glycols, sodium lauryl sulfate, or mixtures thereof.
Magnesium stearate is particularly preferred for lubrication and as
a component to aid in setting the soft chews after molding.
[0021] Humectants illustratively include glycerol and propylene
glycol, and wetting agents include cetyl alcohol and glycerol
monostearate. Glycerin is a preferred humectant useful in
maintaining the softness of the soft chew over the shelf life of
the product. Glycerin is a clear, colorless, odorless, viscous,
hygroscopic liquid.
[0022] Vegetable oils (such as corn, safflower, cottonseed, soybean
and olive oils) may also be utilized to lubricate the chew mixture
and maintain its softness. Oil also aids in flavor palatability. A
particularly preferred oil is soybean oil.
[0023] Paraffin wax or polyethylene glycol 8000 (carbowax) will
preferably be included in the soft chew mixture before molding at
1.0% to 3.0%. If wax is used, it is melted at 50.degree. C. before
being added to the soft chew mixture after mixing. After molding,
the soft chews with the added wax will set-up, usually over a
period of 8 to 24 hours. The wax congeals quickly, softens the chew
mixture, and prevents the soft chew units from sticking together
after molding.
[0024] Additional softening agents utilized are those which limit
density and hardness of the soft chew product. Such agents may
include polysaccharides and fiber. A polysaccharide may be included
in the form of a complex food such as a fruit, a plant starch such
as potato or tapioca starch. Polysaccharide may also be provided
separately, for example, in the form of chondroitin sulfate or
glucosamine HCl.
[0025] Fiber may be also provided as filler or as a bulking agent
and to provide or maintain porosity in the soft chew. Fibers used
to this end may be derived from fruits, grains, legumes, vegetables
or seeds, or provided in forms such as wood fiber, paper fiber or
cellulose fiber such as powdered cellulose fiber. A particularly
preferred such bulking agent for use in the invention is bran, such
as oat bran.
[0026] Other bulking agents that may be utilized include any food
grade material, including hydrocolloid thickeners and binders, such
as gum arabic, pectins, modified starches, alginates, carrageenans,
xanthan gums, carboxymethylcellulose, methylcellulose,
hydroxyethylcellulose, hydroxypropylcellulose,
hydroxypropylmethylcellulose, propylene glycol alginate,
polyvinylpyrrolidone (PVP), carboxyvinyl polymers (such as
Carbopol.RTM.), polyethylene oxide polymers (such as Polyox.RTM.),
talc, dicalcium phosphate, and antacids.
[0027] Binders utilized in soft chews may be a sticky substance or
a substance which becomes sticky in combination with other
ingredients such as water, but will preferably give the soft chew
product a food-like texture. In general, binders may include
molasses, corn syrup, peanut butter, food gum, a starch such as
potato starch, tapioca starch or corn starch, honey, maple syrup
and sugars. Preferred binders for use in soft chews of the
invention are starches and powdered sweeteners.
[0028] A particularly preferred binder is Starch 1500, a
pregelatinized starch made by Colorcon Corporation. Pregelatinized
starch is a starch that has been chemically and/or mechanically
modified to rupture all or part of the starch granules and so
render the starch flowable. It contains 5% of free amylase, 15% of
free amylopectin and 80% unmodified starch. The source is from
corn.
[0029] Powdered sugar (sucrose) serves well as a sweetener as well
as a binder. Sucrose is obtained from either sugar cane or sugar
beets. Salt and/or other spices may be added as appropriate, with
salt being especially preferred to enhance flavor.
[0030] A preservative such as potassium sorbate, sodium benzoate or
calcium propionate may be included in order to retard growth of
microorganisms and fungi. Tenox 4 is a combination of BHA and BHT
anti-oxidants, made by Eastman Chemicals. It is a preferred and
convenient preservation system.
[0031] Vitamins may be provided according to the nutritional
requirements of the target animal, and may be provided as an
element of oils utilized. Vitamins are also present in various oils
that may be added as softening agents; for example, canola oil,
corn oil, soybean oil and vegetable oil.
[0032] Excipients that may be utilized include starches, cellulose,
or derivatives or mixtures thereof, in amounts ranging, for
example, from about 1 to about 60 percent (w/w), preferably from
about 2 to about 50 percent, more preferably from about 15 to 50
percent. For example, the excipient may consist of sodium starch
glycolate, pregelatinized corn starch (Starch 1500), crospovidone
(Polyplasdone XL.TM., International Specialty Products), and
croscarmellose sodium (Ac-Di-Sol.TM., FMC Corp.), and derivatives
thereof. Excipients may be used to create a trituration of an
active. For example, to create a 10% trituration, 100 grams of the
active is combined with 900 grams of an excipient, such as a
preferred excipient, Starch 1500. The dry mixture is fluidized and
is then preferably coated.
[0033] If a coating is to be provided (to help protect the
stability of the active and mask its taste), food grade coatings
are preferred, such as an aqueous film coat from Colorcon
Corporation sold as OPADRY.TM.. OPADRY is a methylcellulose based
product with a plasticizer and pigment. Since the coating is
aqueous based, no special handling precautions are required during
manufacture of the soft chew. However, after administration, the
aqueous film coat will start to erode and/or dissolve within
minutes when exposed to water or other liquids in the stomach.
Therefore, disintegration and dissolution of the soft chew should
not be delayed after it is administered to the subject.
[0034] Any orally administrable active drug or other biologically
active compound may be provided in the soft chews of the invention.
Those of ordinary skill in the human and/or veterinary
pharmaceutical arts will be entirely familiar with the identity of
such actives which may include, without limitation, antibiotics,
analgesics, antivirals, antifungals, anthelmetics, endo- and
ecto-parasticides, hormones and/or derivatives thereof,
anti-inflammatories (including non-steroidal anti-inflammatories),
steroids, behavior modifiers, vaccines, antacids, laxatives,
anticonvulsants, sedatives, tranquilizers, antitussives,
antihistamines, decongestants, expectorants, appetite stimulants
and suppressants, minerals and vitamins.
[0035] The amounts of each of the components in the final product
may be varied considerably, depending upon the nature of the drug,
the weight and condition of the subject treated, and the unit
dosage desired. Those of ordinary skill in the art will be able to
adjust dosage amounts for particular actives in the soft chews in
light of the teachings of this disclosure. Generally, however, the
active may be provided by range in weight based on the total weight
of the composition from about 0.001% to 75% (w/w), more preferably
0.095% to 40%, and most preferably not in excess of 50%. For
example, for administration of an anthelmetic to dogs, such as
ivermectin for treatment of heartworms (see, Example 1) triturated
with starch could be added to comprise 31.2% of the foregoing
mixture.
[0036] The formula described for the exemplary product may be
easily modified for delivery of actives to other species. For
example, equine soft chews may be based on the same basic formula,
substituting molasses powder, oat bran and apple for the bacon.
Flavorings particularly appealing to cats include artificial soy
based compounds with a fish-like flavor. Human recipients may
prefer sweeter flavorings, such as sugars or molasses.
[0037] The soft chews of the invention may be packaged individually
for administration and stable storage. Examples of suitable
packaging materials include HDPE bottles or foil/foil
packaging.
B. Processes for Manufacturing Soft Chews of the Invention
[0038] Active and inactive ingredients for a soft chew of the
invention are added to a mixing vessel of a horizontal mixer
capable of blending the material and casting it against the side of
the mixing vessels. This action permits the ingredients to be well
and consistently blended without application of heat or addition of
pharmaceutical grade water to the mixture.
[0039] Horizontal mixers generally comprise a mixing chamber, an
elongated, horizontal mixing shaft which rotates, and a plurality
of mixing tools which depend generally perpendicularly from the
horizontal shaft to rotate around the inside of the chamber. (See,
e.g., U.S. Pat. No. 5,735,603, the disclosure of which is
incorporated herein by this reference). The mixing tools are
configured and dimensioned as required for the mixing process to
follow the shape of the chamber walls as rotated for proper mixing
of all of material present. Some such mixing chambers are
cylindrically shaped, while others are trough-shaped, such as
mixers which are commonly referred to in the art as double-arm
mixers or ribbon mixers.
[0040] In general, a horizontal mixer will have a horizontal mixing
shaft extending out of the chamber at both ends. In a motorized
mixer, at one end of the shaft, referred to as the drive end, the
shaft is operably coupled to a drive motor for rotating the shaft.
At the drive end, the shaft is typically coupled through a bearing
structure located between the drive motor and the chamber. The
bearing structure provides support of the shaft drive end and also
ensures smooth rotation. A separate seal structure is often
provided further in along the length of the shaft to seal it
against leakage of material into and out of the mixing chamber.
[0041] A particularly preferred mixer for use in the invention used
is a plough type ribbon mixer with optional agitating blades, sold
under the FXM SERIES.TM. trademark by Littleford Day Corporation. A
200 kg capacity blender can be used for commercial scale
production, and is capable of producing as little as 50 kg of chew
mixture for research scale work. No heat is applied during mixing,
and the blended product produced has a consistent weight,
ingredient distribution and texture from batch to batch.
[0042] Preferably, dry ingredients of the chew mixture are blended
first, then liquid ingredients (e.g., humectants and softening
agents) are added and blended therein to form a thoroughly blended
mixture. After blending, the chew mixture is discharged from a port
through the blender into a suitable container for processing into
individual dosage units with a forming machine.
[0043] A variety of forming equipment may be utilized in the
invention, but those particularly preferred for use are molding
machines developed for use in producing molded food products, such
as pre-formed hamburger patties and chicken nuggets. For example,
the molding machines disclosed in U.S. Pat. Nos. 3,486,186;
3,887,964; 3,952,478; 4,054,967; 4,097,961; 4,182,003; 4,334,339;
4,338,702; 4,343,068; 4,356,595; 4,372,008; 4,535,505; 4,597,135;
4,608,731; 4,622,717; 4,697,308; 4,768,941; 4,780,931; 4,818,446;
4,821,376; 4,872,241; 4,975,039; 4,996,743; 5,021,025; 5,022,888;
5,655,436; and 5,980,228 (the disclosures of which are incorporated
herein) are representative of forming equipment that may be
utilized in the invention.
[0044] Preferred forming equipment for use in the invention
includes the Formax F6.TM. molding machine made by the Formax
Corporation. The F6 machine has the capabilities of 60 stokes per
minute. A square forming die of 6'' by 6'' can be used to form
approximately 16 chunk-like soft chew units per stroke, each unit
weighing 4 grams and being approximately 5/8'' by 5/8'' in size.
Dies for production of other shapes (e.g., bone shaped chews) may
also be utilized.
[0045] In such a machine, a rotary valve opens to cause the chew
mixture to flow through fill slots beneath into a first set of mold
cavities. A mold plate is advanced, forcing the chew mixture into a
second set of cavities, then the mold plate is retracted so the
cycle can begin again. The molding mechanism is hydraulic, and
works by light pressure on the molding plate, without application
of heat.
[0046] A knockout mechanism is provided with cups that align with
the cavities to eject molded mixture. from all the mold plate
cavities simultaneously. For molding soft chews of the invention,
such a machine could produce an output per hour of approximately
57,600 units, assuming use of a blender mixture yielding 50,000
units per sub batch. Each batch of chews may be packaged in bulk
or, preferably, each chew is then individually packaged for
storage.
[0047] The invention having been fully described, its practice is
illustrated by the examples provided below. Standard abbreviations
and measurements apply throughout the examples unless a contrary
definition is given. The examples do not limit the scope of the
invention, which is defined entirely by the appended claims.
EXAMPLE 1
Ivermectin Soft Chew for Treatment of Heartworms
[0048] An example of a soft chew suitable for delivery of an active
is set forth in Formula 1 below. TABLE-US-00001 Formula 1:
Concentration % w/w Ingredient 47.90 Starch 1500, USP 1.0 Powdered
Sugar, USP 2.0 Oat Bran, Food Grade 15.0 Bacon Flavor (Provesta
.TM. 356), Food Grade 2.0 Polyethylene glycol 8000 20.0 Glycerin,
USP 7.0 Vegetable Oil (soybean), USP 0.1 Tenox 4, Food Grade 1.0
Magnesium Stearate, USP 1.0 Yeast Flavoring 3.0 Croscarmellose,
sodium N.F. 0.001 FD&C Carmine Dye
EXAMPLE 2
Method for Coating Active Ingredients of Soft Chews of the
Invention
[0049] The active (ivermectin) was milled and screened through a 20
mesh screen. A 10% trituration was made by dry blending 100 grams
of ivermectin and 900 grams of Starch 1500 for 3 to 5 minutes. The
resultant trituration was fluidized in a fluidized bed column and a
food grade coating (OPADRY.TM.) was applied using a Wurster coater,
a top spray fluidized coater, or other suitable device.
EXAMPLE 3
Exemplary Method of Manufacture for Soft Chews of the Invention
[0050] All dry ingredients listed in Examples 1 and 2 except the
oat bran were sifted through a 20 mesh screen, then placed with the
bran into the mixing vessel of a horizontal mixing blender and
mixed for 5 minutes. The glycerin was added slowly followed by the
slow addition of the vegetable oil and Tenox 4 which had been added
to the oil. The product was mixed for 3 minutes. The PEG 8000 was
melted then added relatively quickly to the chew mixture, which was
then mixed for an additional minute. The mixture resembled a
"cookie dough-like" appearance.
[0051] The mixture was formed into individual chunks using a Formax
F6.TM. molding machine with dies for production of chunk-like
shapes, and packaged for storage.
[0052] The invention having been fully described, its scope is
defined by the claims appended hereto.
* * * * *