Note: Descriptions are shown in the official language in which they were submitted.
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"FLAVORED PRODUCT CONTAINING MEDICAMENT
OR OTHER ACTIVE AGENT"
S
This patent application is a continuation-in-part ofU.S. Serial No.
09/421,905,
filed on October 20, 1999, entitled "Powder Pharmaceutical Formulations."
BACKGROUND OF THE INVENTION
The present invention generally relates to the delivery of medicaments and
other
agents. More specifically, the present invention relates to the delivery of
medicaments
and agents using products that provide a pleasant taste.
It is of course known to provide agents to individuals for various purposes.
These
agents can be used to treat diseases and as such are typically referred to as
drugs or
medicaments. Likewise, drugs or medicaments can be used for prophylactic
purposes.
Still, it is known to provide agents to an individual for a variety of non-
medical purposes
including enhancing performance or maintaining or initiating alertness. There
are a
great variety of such agents. These agents run the gamut from stimulants such
as caffeine
to drugs such as analgesics, tranquilizers, cardiovascular products, insulin,
etc. Some
such agents are taken on an as needed basis while other agents must be taken
at regular
intervals by the individual.
Typically, drugs (medicaments) are administered parenterally or enterally. Of
course, parenteral administration is the administration of a drug
intravenously directly
into the blood stream. Enteral refers to the administration of a drug into the
gastrointestinal tract. In either case, the goal of the drug administration is
to move the
drug from the site of administration towards the systemic circulation.
Except when provided intravenously, a drug must traverse several semipermeable
cell membranes before reaching general circulation. These membranes act as a
biological
barrier that inhibits the passage of drug molecules. There are believed to be
four
processes by which drugs move across a biological barrier: passive diffusion;
facilitated
diffusion; active transport; and pinocytosis.
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Passive diffusion is the transport across the cell membrane wherein the
driving
force for the movement is the concentration gradient of the solute. In orally
administered
drugs, this absorption occurs in the small intestines. Facilitated diffusion
is believed to
be based on a carrier component that combines reversibly with the substrate
molecule at
the cell membrane exterior. The carrier substrate complex diffuses rapidly
across the
membrane with release of the substrate at the interior surface. Active
transport requires
an energy expenditure by the cell and appears to be limited to agents with
structural
similarities to normal body constituents. These agents are usually absorbed
from specific
sites in the small intestines. Pinocytosis refers to the engulfing of
particulars or fluid by
a cell. It is believed to play a minor role in drug transport. Merck Manual,
16th Edition,
pp. 2598-2599.
In determining the efficacy of a drug and the effectiveness of the use of a
drug to
treat a disease, drug absorption is a critical concern. Drug absorption refers
to the
process of drug movement from the site of administration toward the systemic
circulation.
Oral administration of drugs is by far the most common method. When
administered orally, drug absorption usually occurs due to the transport of
cells across
the membranes of the epithelial cells within the gastrointestinal tract.
Absorption after
oral administration is confounded by numerous factors. These factors include
differences
down the alimentary cannel in: the luminal pH; surface area per luminal
volume;
perfusion of tissue, bile, and mucus flow; and the epithelial membranes. See
Merck
Manual at page 2599.
A further issue effecting the absorption of orally administered drugs is the
form
of the drug. Most orally administered drugs are in the form of tablets or
capsules. This
is primarily for convenience, economy, stability, and patient acceptance.
Accordingly,
these capsules or tablets must be disintegrated or dissolved before absorption
can occur.
There are a variety of factors capable of varying or retarding disintegration
of solid
dosage forms. Further, there are a variety of factors that effect the
dissolution rate and
therefore determine the availability of the drug for absorption. See Merck
Manual at
page 2600.
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Parental administration allows for the direct placement of the drug into the
blood
stream. This usually insures complete delivery of the dose to the general
circulation.
However, administration by a route that requires drug transfer through one or
more
biologic membranes to reach the blood stream precludes a guarantee that all of
the drug
S will eventually be absorbed. Even with parental administration, because
capillaries tend
to be highly porous, the perfusion (blood flow/gram of tissue) is a major
factor in the rate
of absorption. Thus, the injection site can markedly influence a drug's
absorption rate;
e.g., the absorption rate of diazepam injected IM into a site with poor blood
flow can be
much slower than following an oral dose. See Merck Manual at page 2601.
Not only is drug absorption an issue in drug delivery, but, also the
bioavailability
of the drug is also critical. Bioavailability is defined as type rate at which
and the extent
to which the active moiety (drug or metabolite) enters the general
circulation, thereby
gaining access to the site of action. Bioavailability depends upon a number of
factors,
including how a drug product is designed and manufactured, its physicochemical
properties, and factors that relate to the physiology and pathology of the
patient. See
Merck Manual at page 2602.
When a drug rapidly dissolves from a drug product and readily passes across
membranes, absorption from most site administration tends to be complete. This
is not
always the case for drugs given orally. Before reaching the vena cava, the
drug must
move down the alimentary cannel and pass through the gut wall and liver, which
are
common sites of drug metabolism. Thus, the drug may be metabolized before it
can be
measured in the general circulation. This causes a decrease in drug input that
is called
the first pass effect. A large number of drugs show low bioabilities owing to
an extensive
first pass metabolism. The two other most frequent causes of low
bioavailability are
insuff cient time in the GI tract and the presence of competing reactions. See
Merck
Manual at page 2602.
Bioavailability considerations are most often encountered for orally
administered
drugs. Differences in bioavailability can have profound clinical significance.
Although parental administration does provide a method for eliminating a
number
of the variables that are present with oral administration, parental
administration is not
a preferable route. Typically, parental ~dmiratration requires the use of
medical
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personnel and is just not warranted nor practical for the administration of
most agents and
drugs, e.g., analgesics. Even when required parenteral administration is not
preferred due
to patient concerns including comfort, infection, etc., as well as the
equipment and costs
involved. However, despite best efforts certain therapies require parenterally
injected
drugs. For example, research for decades has focused on an attempt to deliver
insulin to
an individual through a non-parental means. Despite such efforts today insulin
is still
only administered intravenously.
A limited number of medicaments have been administered in the form of a
powder. For example, headache powders have been used to provide an enteral
method
for the delivery of aspirin and other analgesics. Examples of such headache
powders are
marketed under the brand names BG and Dr. Goodys. These powders are very
bitter and
typically are not the desired method to enterally ingest an analgesic.
It is of course known to place medicaments or active agents in a tablet form.
Typically the tablets, such as aspirin, are swallowed immediately after being
placed in
1 S the mouth. In this regard, these products typically have a bitter taste
and are not designed
to dissolve in the consumer's mouth or be chewed.
There is therefore a need for an improved method of delivering drugs and
agents
to an individual.
SUMMARY OF THE INVENTION
The present invention provides improved methods for delivering a medicament
or agent to an individual. Improved formulations including medicaments and
agents are
also provided by the present invention. To this end, compacted powders are
provided
including medicaments or agents. The medicament or agent, in a powder form, is
mixed
with at least a masking agent, the resultant powder is then compressed or
compacted into
a defined shape. It has been found that the masking agent and medicament in a
compacted powder form provides a product that covers up the bitter and bad
flavors
produced by the medicament or agent while allowing the product to be delivered
through
the buccal cavity.
The present invention allows a variety of medicaments and agents to be
delivered
directly into the systemic system of the individual through the oral mucosa
contained in
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the buccal cavity. Such a method can greatly enhance the absorption of the
drug into the
systemic system as well as the bioavailability of the drug within the system.
Absorption
of the drug is further enhanced by allowing the consumer to hold the compacted
powder
in the mouth and chew same for 1 or 2 minutes or longer if comfortable.
To this end, in an embodiment, the present invention provides a compacted
powder including medicament that is designed to dissolve in the mouth of the
user or
that can be chewed. The compacted powder medicament includes a sufficient
amount
of a masking agent to improve the organoleptic properties of the powdered
formula.
Preferably, the powder includes a release agent.
In an embodiment, the medicament is chosen from the group consisting of
analgesics; muscle relaxants; antihistamines; decongestants; antacids; anti-
inflammatories; antibiotics; antivirals; stimulants; psychotherapeutic agents;
and
cardiovascular agents.
In an embodiment, the masking agent is chosen from the group consisting of
zinc gluconate; ethyl maltol; glycine; acesulfame-K; aspartame; sucrolose;
saccharin;
fructose; xylitol; spray dried licorice root; glycyrrhizin; sodium gluconate;
glucono delta
lactone; vanillin; normal and high-potency sweeteners; and a variety of
appropriate
flavors.
In an embodiment, the formulation creates a saliva content of medicament of at
least 5 ppm to about 66% medicament by weight in the saliva, depending on the
medicament.
In an embodiment, the release agent is chosen from the group consisting of
calcium and magnesium stearate.
In another embodiment of the present invention, the present invention provides
a method for delivering a medicament to an individual comprising the steps of
providing a compressible formulation that includes a medicament in powder form
and
a sufficient amount of a masking agent to provide acceptable organoleptic
properties, the
compressible formulation being compressed into a defined structure; and
allowing at least
a portion of the defined structure to dissolve in a mouth of an individual to
cause the
medicament to be released from the formulation into a buccal cavity of the
individual.
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In an embodiment, the compressible formulation includes a compressible mono
or di-saccharide, e.g., dextrose or sucrose, or a combination, or compressible
sugar
alcohols, e.g., sorbitol, mannitol, and iso-maltitol. The quantity of which is
chosen so
that it masks the taste of the medicaments.
In a further embodiment, the present invention provides a method of enhancing
an individual's performance, the method comprising the steps of providing a
compressible powder formulation including a performance enhancing amount of
caffeine
in powder form and a masking agent; compressing the powder into a solid
structure; and
allowing at least a portion of the solid structure to dissolve in the mouth of
the individual
not more than ten minutes before the performance.
In an embodiment, the performance to be enhanced is athletic.
In an embodiment, the performance to be enhanced is cognitive.
In an embodiment, the performance to be enhanced is alertness.
In an embodiment, the powder formulation is placed in the buccal cavity not
more
1 S than S minutes before the performance.
Yet further, the present invention provides a method of increasing the
stimulatory
effect of a stimulant that has been previously ingested by an individual
comprising the
steps of: providing a compacted formulation that contains a stimulant and a
masking
agent; and placing the compacted formulation into the buccal cavity causing
the stimulant
to be released by the compacted formulation into an oral mucosa located in a
buccal
cavity of the individual.
In another embodiment, the present invention provides a compressible powder
formulation comprising a powder medicament and a sufficient amount of a
masking
agent to provide a powder formulation having acceptable organoleptic
properties.
In a further embodiment of the present invention, a method of delivering a
medicament is provided. The method comprising the steps of providing a
compressible
powder formulation including a medicament in powder form and a sufficient
amount of
a masking agent to mask any offensive tastes that are associated with the
medicament;
compacting the compressible formulation into a defined structure; placing the
defined
structure in a buccal cavity of an individual; and allowing at least a portion
of the defined
structure to dissolve in the buccal cavity.
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In a still further embodiment, the present invention provides a product
including
a medicament. The product includes a compressible powder medicament having an
offensive taste; a sufficient amount of a compressible masking agent to
provide
acceptable organoleptic properties; and a release agent.
Accordingly, an advantage of the present invention is to provide new methods
and
compositions for delivering medicaments or agents to an individual.
Still further, an advantage of the present invention is to provide a method of
delivering medicaments to an individual that provides for increase absorption
and
bioavailability as compared to medicaments that are designed to be absorbed in
the GI
tract.
Further, an advantage of the present invention is to provide a method of
administering a medicament or agent to an individual at a level that is lower
than is
typically administered orally while still achieving the same effect.
Furthermore, an advantage of the present invention is to provide a method for
administering drugs or agents to an individual that heretofore were
administered
parentally.
Additionally, an advantage of the present invention is to provide a method for
administering drugs that is more palatable than current methods.
Another advantage of the present invention is to provide a method for
enhancing
the performance of an individual through the administration of an agent.
Moreover, an advantage of the present invention is to provide improved methods
for drug delivery.
Still, an advantage of the present invention is to provide a method for
creating a
triggering effect that creates a synergistic effect with an agent that is
present in the
systemic circulation of the individual.
Additional features and advantages of the present invention will be described
in
and apparent from the detailed description of the presently preferred
embodiments.
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DETAILED DESCRIPTION OF THE
PRESENTLY PREFERRED EMBODIMENTS
The present invention provides improved methods for delivering medicaments
and other agents to an individual as well as improved formulations including
such
medicaments and agents. Pursuant to the present invention, a medicament or
agent is
contained in a compacted powder formulation that includes a masking agent. As
used
herein, the term "masking agent" includes compounds and agents that alter or
disguise
the taste of a product that is ingested or placed in the mouth. As such, the
term masking
agent includes sweeteners and flavors.
It has been found that by adding a masking agent to a powder formulation, that
a much more palatable formulation, including a powder medicament, can be
provided.
In this regard, even though the medicament in its powder form may be bitter or
have an
offensive taste, the powder matrix of the present invention, including the
masking agent,
will afford a product having acceptable organoleptic properties. It has been
surprisingly
found that by solubilizing a powdered matrix of medicament and masking agent,
this
increases the ability of the masking agent to cover up any bitter and/or bad
flavors
produced by the medicament or agent. By selecting specific masking agents
based on the
bad or off taste produced by the medicament, one can provide a palatable
powder
formulation.
For example, if one is attempting to cover an astringent flavor such as
aspirin, one
would use masking agents found to be effective against astringency such as
fructose and
high-intensity sweeteners, e.g., sucrolose, saccharin, aspartame, and
acesulfame-K. In
the case of a moderately bitter active ingredient, such as caffeine, one would
use
ingredients such as glycine, ethyl maltol, zinc gluconate, licorice root
powder, high-
intensity sweeteners, etc. In the case of a very bad tasking active ingredient
such as
acetaminophen, combinations of these masking agents or larger quantities may
have to
be used in order to combat the undesirable bitterness, e.g., peppermint and a
high-
intensity sweetener.
The masking agents, in an embodiment, are selected from the group consisting
of sucrolose; zinc gluconate; ethyl maltol; glycine; acesulfame-K; aspartame;
saccharin;
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fructose; xylitol; maltitol; isomalt; spray dried licorice root; glycyrrhizin;
sodium
gluconate; glucono delta-lactone; ethyl vanillin; and vanillin.
In a prefer ed embodiment, it has been found that using at least approximately
1.5
grams to about 3 grams of bulk sweetener (e.g., dextrose, sucrose, sorbitol,
and
S isomaltitol) with a high-intensity sweetener provides an excellent masking
agent in
typically envisioned products. This quantity of bulk sweetener masking agent
is able to
mask the bitterness of many medicaments and active agents.
By insuring that the powder formulation includes compressible components, a
solid dosage form of the product can be created. In this regard, the powder
formulation
can be compacted into a pill-like, mint-like, tablet-like, or similar
structure. Preferably
the compacted powder has a matte finish, although if desired, the product can
be coated.
In use, the compacted powder formulation is placed in the mouth of the user.
Due
to the present invention, as the compacted powder formulation begins to
dissolve, it has
acceptable organoleptic properties allowing the consumer to maintain the
product in his
mouth for a sufficient time to allow as much of the product as possible to
dissolve. As
the product dissolves, the powder medicament or agent is released into the
saliva. The
medicament or agent in the saliva then passes through the oral mucosa in the
buccal
cavity. The oral mucosa has a thin epithelium and a rich vascularity. Thus,
the oral
mucosa favors drug absorption.
In contrast to a typically orally ingested drug, wherein the solution is in
contact
too briefly for absorption to be appreciable through the oral mucous, if the
product is
allowed to dissolve in the mouth, an increase in the absorption of the drug is
achieved as
well as an increase in the bioavailability of the drug as compared to typical
oral
administration. It has been found that the drug or agent is absorbed much
quicker when
it is allowed to dissolve in the mouth of the consumer than if it was
swallowed as in a
typical oral administration.
It is believed that less powder medicament or agent can be placed in the
formulation than is typically orally administered to an individual to achieve
an effect and
the same bioequivalence can be achieved.
For example, caffeine is commonly used as a stimulant to alleviate the effects
of
sleep deprivation. It is almost completely metabolized in the liver and
therefore
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classified as. a low clearance, flow independent drug. This means its rate of
inactivation
is unaffected by delivery to the liver and can only be modified by a change in
the hepatic
enzyme activity.
The pharmacokinetics of caffeine have been well documented and there is no
significant difference between oral and intravenous administration. However,
data set
forth in detail below, suggests that the absorption rate constant (Ka) is
significantly
increased when caffeine is administered through chewing gum. This means that
the
caffeine is moving into the systemic circulation at a significantly faster
rate. A similar
change in the onset of dynamic response has also been noted, e.g., alertness
and
performance.
It is believed that for at least certain agents that placing the agent in a
compacted
powder formulation that is placed in the mouth can have a triggering effect on
the agent
that may be in the systemic circulation. For example, it has been found that
with respect
to caffeine that is ingested orally, that after the ingestion of a certain
amount of caffeine,
and the elapse of a certain period of time, that further ingestion of caffeine
has a
negligible effect on the individual. However, it is believed that if caffeine
is placed in
a powdered formulation with caffeine there has been observed a triggering
effect that
appears to create a synergistic effect with the caffeine that is in the
systemic circulation.
It is believed that this triggering effect will also be present with other
agents, e.g.,
analgesics.
It is envisioned, that a variety of different medicaments and other active
agents
can be used in the compacted powder formulation. By the terms "active agent"
the
present invention refers to a compound that has a desired therapeutic or
physiological
effect once ingested and/or metabolized. The therapeutic effect may be one
which
decreases the growth of a xenobiotic or other gut flora or fauna, alters the
activity of an
enzyme, provides the physical relief from a malady (e.g., diminishes pain,
acid reflux,
or other discomfort), has an effect on the brain chemistry of molecules that
determine
mood and behavior. Of course these are just examples of what is intended by
therapeutic
effect. Those of skill in the art will readily recognize that a particular
agent has or is
associated with a given therapeutic effect.
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The active agent may be any agent that is traditionally used as a medicament
and
lends itself to being administered through the oral cavity. Such active agents
may be
vitamins, cancer chemotherapeutics; antimycotics; oral contraceptives,
nicotine, nicotine
replacement agents, minerals, analgesics, antacids, muscle relaxants,
antihistamines,
decongestants, anesthetics, antitussives, diuretics, anti-inflammatories,
antibiotics,
antivirals, psychotherapeutic agents, anti-diabetic agents, and cardiovascular
agents,
bioengineered pharmaceuticals, nutraceuticals, and nutritional supplements.
Vitamins
and co-enzymes that may be delivered using this invention include but are not
limited to
water or fat soluble vitamins such as thiamin, riboflavin, nicotinic acid,
pyridoxine,
pantothenic acid, biotin, flavin, choline, inositol, and paraminobenzoic acid,
carnitine,
vitamin C, vitamin D, and its analogs, vitamin A and the carotenoids, retinoic
acid,
vitamin E, and vitamin K.
Examples of cancer chemotherapeutics agents include, but are not limited to,
cisplatin (CDDP), procarbazine, mechlorethamine, cyclophosphamide,
camptothecin,
ifosfamide, melphalan, chlorambucil, bisulfan, nitrosurea, dactinomycin:
danunorubicin,
doxorubicin, bleomycin, plicomycin, mitomycin, etoposide (VP16), tamoxifen,
taxol,
transplatinum, S-fluorouracil, vincristin, vinblastin, and methotrexate or any
analog or
derivative variant thereof.
Antimicrobial agents that may be used include, but are not limited to,
naficillin,
oxacillin, vancomycin, clindamycin, erythromycin, trimethoprim-
sulphamethoxazole,
rifampin, ciprofloxacin, broad spectrum penicillin, amoxicillin, gentamicin,
ceftriazoxone, cefotaxime, chloramphenicol, clavunate, sulbactam, probenecid,
doxycycline, spectinomycin, cefixime, penicillin G, minocycline, P-lactamase
inhibitors;
meziocillin, piperacillin, aztreonam, norfloxacin, trimethoprim, ceftazidime,
dapsone.
Antifungal agents that may be delivered include but are not limited to
ketoconazole, fluconazole, nystatin, itraconazole, clomitrazole, and
amphotericin B.
Antiviral agents that may be used include but are not limited to acyclovir,
trifluridine,
idoxorudine, foscamet, ganciclovir, zidovudine, dideoxycytosine,
dideoxyinosine,
stavudine, famciclovir, didanosine, zalcitabine, rifimantadine, and cytokines.
Antacids include cimetidine, ranitidine, nizatidine, famotidine, omeprazole,
bismuth antacids, metronidazole antacids, t: ~racy.;,ine antacids,
clarthromycin antacids,
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hydroxides of aluminum, magnesium, sodium bicarbonates, calcium bicarbonate,
and
other carbonates, silicates, and phosphates.
Antihistamines are represented by, but are not limited to, cimetidine,
ranitidine,
diphenydramine, prylamine, promethazine, chlorpheniramine, chlorcyclizine,
S terfenadrine, carbinoxamine maleate, clemastine fumarate, diphenhydramine
hydrochloride, dimenhydrinate, prilamine maleate, tripelennamine
hydrochloride,
tripelennamine citrate, chlorpheniramine maleate, brompheniramine maleate,
hydroxyzine pamoate, hydroxyzine hydrochloride, cyclizine lactate, cyclizine
hydrochloride, meclizine hydrochloride, acrivastine, cetirizine hydrochloride,
astemizole,
levocabastine hydrochloride, and loratadine.
Decongestants and antitussives include agenis such as dextromethorphan
hydrobromide, levopropoxyphene napsylate, noscapine, caretapentane,
caramiphen,
chlophedianol, pseudoephedrine hydrochloride, pseudoephedrine sulfate,
phenylephidrine, diphenhydramine, glaucine, pholcodine, and benzonate.
Anesthetics include etomidate, ketamine, propofol, and benodiazapines (e.g.,
chlordiazepoxide, diazepame, clorezepate, halazepam, flurazepam, quazepam,
estazolam,
triazolam, alprozolm, midazolam, temazepam, oxazepam, lorazepam), benzocaine,
dyclonine, bupivacaine, etidocaine, lidocaine, mepivacaine, promoxine,
prilocaine,
procaine, proparcaine, ropivacaine, tetracaine. Other useful agents may
include
amobartital, aprobarbital, butabarbital, butalbital mephobarbital,
methohexital,
pentobarbital, phenobarbital, secobarbital, thiopental, paral, chloralhydrate,
ethchlorvynol, clutethimide, methoprylon, ethinamate, and meprobarnate.
Analgesics include opioids and other medicaments such as morphine, mepidine,
dentanyl, sufentranil, alfentanil, aspirin, acetaminophen, ibuprofen,
indomethacine,
naproxen, atrin, isocome, midrin, axotal, firinal, phrenilin, ergot, and ergot
derivatives
(wigraine, cafergot, ergostat, ergomar, dihydroergotamine), imitrex, and
ketoprofen.
Diuretics include but are not limited to acetazolamide, dichlorphenamide,
methazolamide, furosemide, bumetanide, ethacrynic acid torseimde, azosemide,
muzolimine, piretanide, tripamide, bendroflumethiazide, benthiazide,
chlorothiazide,
hydrochlorothiazide, hydroflumethiazide, methyclothiazide, polythiazide,
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trichlormethiazide, indapamide, metolazone, quinethazone, amiloride,
triamterene, sprion
olactone, canrenone, and potassium canrenoate.
Anti-inflammatories include but are not limited to salicylic acid derivatives
(e.g.,
aspirin), indole and indene acetic acids (indomethacin, sulindac, and
etodalac) heteroaryl
S acetic acids (tolmetin diclofenac and ketorolac) aryl propionic acid
derivatives
(ibuprofen, naproxen, ketoprofen, fenopren, oxaprozine), anthranilic acids
(mefanamic
acid, meclofenamic acid) enolic acids (piroxicam, tenoxicam, phenylbutazone,
and
oxyphenthatrazone).
Psychotherapeutic agents include thorazine, serentil, mellaril,
millazinetindal,
permitil, prolixin, trilafon, stelazine, suprazine, taractan, navan, clozarill
haldol, halperon,
loxitane, moban, orap, risperdal, alprazolam, chordiaepoxide, clonezepam,
clorezepate,
diazepam, halazepam, lorazepam, oxazepam, prazepam, buspirone, elvavil,
anafranil,
adapin, sinequan, tofranil, surmontil, asendin, norpramin, pertofrane,
ludiomil, pamelor,
vivactil, prozac, luvox, paxil, zoloft, effexor, wellbutrin, serzone, desyrel,
nardil, parnate,
1 S eldepryl.
Cardiovascular agents include, but are not limited to, nitroglycerin,
isosorbide
dinitrate, sodium nitroprisside, captopril, enalaprill, enalaprilat,
quinapril, lisinopril,
ramipril, losartan, amrinone, linnone, vesnerinone, hydralazine, nicorandil,
prozasin,
doxazosin, bunazosin, tamulosin, yohimbine, propanolol, metoprolol, nadolol,
atenolol,
timolol, esmolol, pindolol, acebutolol, labetalol, phentolamine, carvedilol,
bucindolol,
verapamil, nifedipine, amlodipine, and dobutamine, or a sexual dysfunction
agent like
sildenafil citrate (Viagra).
It is envisioned that depending on the active agent or medicament, the
resultant
product can be used to treat inter alias coughs, colds, motion sickness;
allergies; fevers;
pain; inflammation; sore throats; cold sores; migraines; sinus problems;
diarrhea;
diabetes, gastritis; depression; anxiety, hypertension; angina, and other
maladies and
symptoms. Also these gums may be useful in ameliorating cravings in substance
abuse
withdrawal or for appetite suppression. Specific active agents or medicaments
include
by way of example and limitation: caffeine, aspirin, acetaminophen; ibuprofen;
ketoprofen; cimetidine, ranitidine, famotidine, dramamine, omeprazole,
dyclonine
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hydrochloride, chlorpheniramine maleate, pseudoephedrine hydrochloride,
dextromethorphan hydrobromide, benzocaine, sodium naproxen, and nicotine.
Nutraceuticals and nutritional supplements may also be added to the product as
active agents. Among these are herbs and botanicals that include, but are not
limited to,
capsicum, chamomile, cat's claw, echinacea, garlic, ginger, ginko, various
ginseng, green
tea, golden seal, kava kava, nettle, passion flower, saw palmetto, St. John's
wont, and
valerian. Also included are mineral supplements such as calcium, copper,
iodine, iron,
magnesium, manganese, molybdenum, phosphorous, selenium, and zinc. Other
nutraceuticals that also can be added to chewing gum as active agents are
benzoin, fiucto-
oligosaccharides, glucosamine, grapeseed extract, guarana, inulin,
phosphotidylserine,
phytosterols, phytochemicals, isoflavones, lecithin, lycopene, oligofiuctose,
polyphenol,
and psyllium as well as weight loss agents such as chromium picolinate and
phenylpropanolamine.
Preferably, the agents or medicaments are contained in the powder formulation
1 S at levels of approximately 50 micrograms to 1000 milligrams. The specific
levels will
depend on the active ingredient. For example, if chromium picolinate is the
active
ngredient in an embodiment, it would be present at a level of approximately 20
to about
50 micrograms per dosage; aspirin would be preset at a level of approximately
SO to
about 650 milligrams per dosage; caffeine would be preset at a level of
approximately
20 to about 600 milligrams per dosage; and acetaminophen would be preset at a
level of
approximately 87 to about 1000 milligrams per dosage.
The level of medicament or agent in the compacted powdered formulation is
selected so as to create, when the compacted powder formulation is placed in
the mouth,
a sufficiently high concentration of the medicament or agent in the saliva.
For example, when the agent is a stimulant such as caffeine, the level of the
stimulant in the compacted powder formulation should be such that it creates a
saliva
content of stimulant of approximately 1% to about 66% after the formulation is
placed
in the mouth. At this level, a sufficient amount of stimulant will be
delivered to the user
to create the effects set forth in the application. If a medicament is used
such as a
medicinal (e.g., analgesics), sufficient medicinal should be present in the
compacted
powder formulation to create a salvia content of approximately 1 % to about
66%. For
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botanicals (e.g., chamomile, kava, kola, nut, ginseng, and Echinacea), the
agent should
be present in a sufficient amount to create a saliva content of approximately
1 % to about
66%. For a metabolizer, for example, chromium picolineate and hydroxi-chitic
acid, the
agents should be present in an amount to create a saliva content of
approximately 1 % to
S about 66%. If the agent is a vitamin or mineral (e.g., phosphatidy serine,
vitamin C, and
zinc), the agent should be present in the amount to create a saliva content of
the vitamin
or mineral of approximately 2%to about 30%.
Pursuant to the present invention, depending on the agent or medicament, the
dosing regiment will change. For example, if the medicament is an analgesic,
the
compacted powdered formulation would be taken on an as needed basis. Of
course,
similar to the oral administration of an analgesic, there would be
restrictions.on the doses
taken, for example, not more often than one powdered formulation every four
hours and
not more often than four to five times a day.
If the agent is a stimulant, such as caffeine, to be used to enhance
performance
than the compacted powdered formulation would be ingested, in a preferred
embodiment
ten minutes or less before the performance.
Sufficient masking agent will be used to improve and provide acceptable
organoleptic properties to the compacted powder product. As used herein to
provide
"acceptable organoleptic properties" means that the compacted powder
formulation will
have a sufficiently pleasant, or at least non-offensive taste, to allow the
consumer to
allow at least a majority of the compacted powder formulation to dissolve in
his mouth.
The amount of masking agent will thereby vary depending on medicament or
agent. Of
course, more than one masking agent can be used, e.g., zinc gluconate and a
sweetener
or flavor.
Generally, it is believed that the masking agent will comprise approximately
50%
to about 99+% by weight of the powder formulation. For example, if the agent
is
caffeine, approximately 10 to about 50 milligrams of masking agent should be
present
per milligram of caffeine; for aspirin, approximately 4 to about 32 milligrams
of
masking agent should be present per milligram of aspirin; and for
acetaminophen,
approximately 4 to about 32 milligrams of masking agent should be present per
milligram of acetaminophen. Of course, more than one masking agent can be
used.
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The medicament or agent can be contained in a variety of different compacted
powder formulation compositions. For example, the formulation can be low or
high
moisture, sugar or sugarless, andlor low calorie.
The formulation can include a water soluble bulk portion and one or more
flavoring agents. The water soluble portion can include bulk sweeteners, high
intensity
sweeteners, flavoring agents, softeners, emulsifiers, colors, acidulants,
fillers,
antioxidants, and other components that provide desired attributes.
Bulk sweeteners, which also can function as the masking agent, include both
sugar and sugarless components. Bulk sweeteners, if present, will typically
constitute
about 50% to about 98% by weight of the formulation. Bulk sugar sweeteners
generally
include saccharide-containing components commonly known in the confectionary
art,
including but not limited to, sucrose, dextrose, maltose, dextrin, dried
invert sugar,
fructose, levulose, glactose, corn syrup solids, and the like, alone or in
combination.
Bulk sugarless sweeteners include, but are not limited to, sugar alcohols such
as sorbitol,
mannitol, xylitol, hydrogenated starch hydrolysates, maltitol, and the like,
alone or in
combination. As noted earlier, in a preferred embodiment, approximately 1.5 to
about
3.0 grams of bulk sweeteners are present in the product.
High intensity artificial sweeteners can also be used, alone or in
combination,
with the above. Preferred sweeteners include, but are not limited to,
sucralose,
aspartame, salts of acesulfame, alitame, saccharin and its salts, cyclamic
acid and its salts,
glycerrhizinate, dihydrochalcones, thaumatin, monellin, and the like, alone or
in
combination. In order to provide longer lasting sweetness and flavor
perception, it may
be desirable to encapsulate or otherwise control the release of at least a
portion of the
artificial sweetener. Such techniques as wet granulation, wax granulation,
spray drying,
spray chilling, fluid bed coating, coacervation, and fiber extension may be
used to
achieve the desired release characteristics.
Combinations of sugar and/or sugarless sweeteners may be used in the
formulation. Additionally, the softener may also provide additional sweetness
such as
with aqueous sugar or alditol solutions. As noted above, depending on the
powder agent
or medicament, sweeteners can comprise a part of, or the entire masking agent.
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If a low calorie formulation is desired, a low caloric bulking agent can be
used.
Examples of low caloric bulking agents include: polydextrose; Raftilose,
Raftilin;
Fructooligosaccharides (NutraFlora); Palatinose oligosaccharide; Guar Gum
Hydrolysate
(Sun Fiber); or indigestible dextrin (Fibersol). However, other low calorie
bulking agents
S can be used.
A variety of flavoring agents can also be used, if desired. If present, the
flavor
can be used in amounts of about 0.5 to about 10 weight percent of the
formulation. As
noted above, depending on the medicament or agent, flavor can comprise a part
of, or
the entire masking agent. Flavoring agents may include essential oils,
synthetic flavors
or mixtures thereof including, but not limited to, oils derived from plants
and fruits such
as citrus oils, fivit essences, peppermint oil, spearmint oii, other mint
oils, clove oil, oil
of wintergreen, anise and the like. Artificial flavoring agents and components
may also
be used. Natural and artificial flavoring agents may be combined in any
sensorially
acceptable fashion.
In addition to the medicament and masking agent, preferably the product
includes
a release agent. The release agent functions to release the product from the
mold or
similai apparatus during compacting or compression of the powder formulation.
A
variety of release agents can be used including calcium and magnesium
stearate.
Preferably, the release agent comprises approximately 0.5% to about 3% by
weight of the
product.
There are a variety of methods for constructing the product of the present
invention. As a first step, generally the formulations would be constructed by
blending
a medicament in powder form with a powder masking agent and other components
as
desired. The powder can then be, for example, made into a compacted product by
conventional tablet forming machines.
The product then would be packaged in bottles, blister packs, strip packs,
roll
wraps, or tins.
By way of example, and not limitation, examples of some product including a
medicament or agent are as follows:
Example No. 1
In egr diem Percen
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Acetaminophen 20.86%
Peppermint Flavor 0.44
Menthol Flavor 0.37
Dextrose 76.07
Sucrolose 0.19
Magnesium Stearate 1.70
Aspartame 0.37
100.00%
Example No. 2
Ingredient Percent
Acetaminophen 10.1 S
Dextrose 87.39
Sucrolose 0.19
Bubble Gum Flavor0.19
Magnesium Stearate 1.70
Aspartame 0.38
100.00%
Example No. 3
Ingredient Grams Percent
Pseudoephedrin 60.00 3.75%
Menthol Flavor 30.00 1.88
Eucalyptus Flavor 2.00 0.13
Aspartame 32.00 2.00
Magnesium Stearate 27.20 1.70
Dextrose 1_ 44~ 90.55
1,600.00 100.00%
It should be understood that various changes and modifications to the
presently
preferred embodiments described herein will be apparent to those skilled in
the art. Such
changes and modifications can be made without departing from the spirit and
scope of
the present invention and without diminishing its attendant advantages. It is
therefore
intended that such changes and modifications be covered by the appended
claims.
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