Note: Descriptions are shown in the official language in which they were submitted.
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EMETIC EMBEDDED CAPSULE
BACKGROUND OF THE INVENTION
[0002] All drugs have the potential to be misused, whether the drugs are
legally prescribed by a
physician, or purchased over-the-counter at a store. When ingested in
excessive quantities,
drugs normally considered safe can cause death or serious bodily damage.
[0003] Accidental and purposeful overdose or death by over consumption of
drugs is a serious
problem. People ingest drugs to attempt suicide and are often successful.
People who suffer
from depression and who have suicidal thoughts are also at high risk for drug
overdose. Drug
addicts ingest and consume quantities of drugs to elicit mind and mood
altering effects,
potentially causing serious injury to their bodies. Children are able to open
containers
containing any variety of drugs and innocently ingest or consume the drugs
without knowledge
of the consequences, even with the advent of tamper proof containers.
[0004] Accidental drug overdose may be the result of misuse of prescription
medicines or
commonly used medications like pain relievers and cold remedies. Between 1970
and 2000,
some 131,000 people died by accidental drug overdose. While a small percentage
(3 percent) of
the deaths were from adverse effects of the right drug taken at the right
dose, 97 percent of the
deaths resulted from medication errors including ingesting a wrong dose, or
accidental overdose
of a drug. According to the National Institute on Drug Abuse, in 1992, almost
6,000 deaths
were the result of accidental overdose of psychoactive and other drugs.
Patients treated with
antidepressant medications, i.e., GSK's WELLBUTRIN and PAXIL (paroxetine),
Eli Lilly's
PROZAC (fluoxetine), Pfizer's ZOLOFT (sertraline), Solvay's LUVOX,10
(fluvoxamine),
Forest Laboratories' CELEXAO (citalopram) and LEXAPRO (escitalopram), Wyeth's
EFFIXOR (venlafaxine), Bristol-Myers Squibb's SERZONBei (nefazodone) and
Organon's
REMERONO (mirtazapine), may have an increased risk of suicidal thoughts and
behaviour.
t0005] Accordingly, there is a great need for dosage forms to prevent
accidental or intentional
overdose of drugs.
[0006] It is known in the art that emetics may be incorporated into drug
compositions, or
admixed with a drug. Following ingestion, the drug and emetic would be
simultaneously
released in the stomach. However, this requires development of formulations
and compositions
which are compatible and otherwise suitable for use with both the drug and the
emetic, and
further requires that the drug and the emetic be chemically compatible with
each other.
Additionally, combining an emetic and drug in a single composition would cause
the emetic and
drug to be released simultaneously following ingestion, thus there is a danger
that a dangerous
or toxic amount of drug can be absorbed into the body prior to emesis of the
drug.
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[0007] U.S. Pat. No. 4,175,/ 19 and 4,529,583 disclose a medicinal composition
whereby a tablet or capsule is coated with an emetic to prevent
accidental or purposeful drug overdose. However, this requires the use of
coating machines
which health care professionals may not have access to.
[0008] Thus a need exists for an emetic dosage form which may be employed for
the delivery
of a wide range of drugs and which permits flexibility in dosing of the drug
and emetic.
[0009] Additionally, a need exists for an emetic dosage form which may be
employed for the
delivery of a wide range of drugs and which permits customized dosing of the
drug and emetic
for individual patients.
[0010] Additionally, a need exists for a method for manufacturing and
administering an emetic
dosage form allowing health care professionals to tailor various drugs in
variable amounts for
individuals that may ingest an overdose of a drug.
[0011] Additienally, a need exists for a method to customize an emetic dosage
to induce
emesis before drugs are absorbed in a human, potentially causing an overdose.
SUMMARY OF THE INVENTION
10012] The present invention provides capsules containing an emetic, which
capsules can
encapsulate a drug, wherein the amount of emetic and the amount of drug is
such that the
number of capsules needed to be ingested to cause emesis is fewer than the
number of capsules
needed to be ingested to cause overdose of the drug, so that if a person takes
an overdose of the
emetic encapsulated drug, he or she will vomit before an amount of drug is
absorbed by the
body which may cause an overdose.
[0013] The present invention is thus directed to a capsule comprising an
emetic.
tool 3a} In a particular embodiment there is provided a hard capsule piece for
encapsulating a drug, wherein the hard capsule piece comprises: an emetic; a
matrix; and
a plasticizer; and wherein said emetic is embedded in the hard capsule piece.
[0014] In one embodiment of the present invention, an emetic embedded piece is
formed from
an admixture comprising a matrix, a plasticizer, and an emetic.
[0015] In another embodiment of the present invention, in emetic embedded
piece is formed
from an admixture comprising a matrix, a plasticizer, and an emetic, the piece
also having a
sub-compartment to hold the same or a different emetic in the admixture.
[0016] In another embodiment of the present invention, an emetic embedded
capsule is formed
with at least one emetic embedded piece, and a second capsule piece. An emetic
embedded
capsule can also be formed by encapsulating a drug within a sub-chamber of an
emetic
embedded piece, and an emetic is encapsulated within the main chamber of the
capsule.
[0017] In still another embodiment of the present invention, an emetic
embedded capsule is
suitable for use in a method of inducing emesis in the body of a being to
preclude injury or
death from accidental or intentional overdose of a drug, which is normally of
the type which if
ingested properly (i.e., by prescription or instructions) is safe, but if
ingested in excessive
quantities is potentially toxic, potentially lethal, toxic, or lethal.
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[0018] In still another embodiment of the present invention, a drug is
encapsulated within an
emetic embedded capsule to form an emetic encapsulated drug.
[0019] In still another embodiment, a central and/or gastric emetic is used as
an emetic.
[0020] In still another embodiment, an emetic having both central and gastric
effect is used in
an emetic embedded capsule or an emetic embedded piece.
[0021] In still another embodiment of the present invention, an emetic
embedded capsule or
piece can contain different amount of emetics having a particular emetic dose,
so that an
appropriate emetic embedded capsule or piece can be selected for a particular
drug, for a
particular drug dosage, and/or for a particular patient.
[0022] In still another embodiment, different color emetic embedded capsules
or pieces may
signify different amounts of emetics contained within an emetic embedded
capsule or piece.
[0023] In still another embodiment of the present invention, emetic embedded
capsules or
pieces may contain different types of emetics or mixtures of emetics, so that
an appropriate
emetic embedded capsule or piece can be selected for a particular drug, for a
particular drug
dosage, or for a particular patient.
[0024] In still another embodiment, different color emetic embedded capsules
or pieces may
signify different types of emetic chemicals present in an emetic embedded
capsule or piece.
[0025] In still another embodiment of the present invention, a laxative may be
substituted for
the emetic.
[0026] In still another embodiment of the present invention, the capsules may
contain
fragrances and flavors.
[0027] In still another embodiment of the present invention, the capsule
contains an inert
material so that when the capsule is ingested in normal quantities, the emetic
can be passed
through the gastrointestinal tract with aid of the inert material, and the
emetic is not
substantially absorbed into the body. However, when the capsule is ingested in
quantities to
induce emesis, then the inert material will not prevent emesis.
[0028] Other objects of the present invention will become apparent from a
review of the
present specification.
DESCRIPTION OF THE DRAWINGS
[0029] Fig. 1 is an emetic embedded capsule in accordance with the present
invention.
DETAILED DESCRIPTION OF THE INVENTION
[0030] As shown in Fig. 1, capsules 2 for dosing of drugs are well known in
the art. A capsule,
i.e., a hard gelatin or hard gel capsule, generally comes in two pieces, a
male piece 4 and a
female piece 6, whereby both pieces cooperatively operate to engage another,
generally the
male piece 4 fitting into the female piece 6. Generally, the two pieces each
have an outer
circumference, a thickness, and an inner circumference. The inner
circumference 6A of the
female piece 6 is slightly smaller than the outer circumference 4A of the male
piece 4 so that the
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male piece engages the female piece to form a seal to prevent leakage of the
contents of the
capsule. Optionally, the two pieces may be the same or identical size having
means to engage
one another, such means being known in the art.
[0031] Generally when the two pieces become engaged with one another, a single
compartment
is formed within the capsule. Referring to Fig. 1, it is known in the art that
each capsule
piece may also contain a separate smaller compartment 12 (shown as a sub-
compartment in
male piece 4), in which case a capsule would have a main compartment 10 and a
sub-
compartment 12 if one of the two piece have a sub-compartment, and a main
compartment and
two sub-compartments if each of the pieces has a sub-compartment. For example,
the sub-
compartment may be created by insertion of an inner dividing shell over a
desired material, e.g.,
an emetic or drug. The sub-compartment 12 may be filled with same or different
materials as
the main compartment 10.
[0032] The composition of capsules and capsule pieces are well known in the
art. Capsules
and capsule pieces typically contain a matrix and a plasticizer.
[0033] A matrix is a material that is capable of forming sheets or a film. The
matrix may
comprise gelatin, cellulose, and cellulose derivatives, carbohydrate polymers,
polyvinyl
polymers, and other materials known in the art, for example, see U.S. Pat. No.
5,756,123
disclosing a capsule shell comprising hydroxypropylmethyl cellulose, U.S. Pat.
No. 6,214,376
disclosing a capsule having a hydrocollid as a matrix, and U.S. Pat. No.
4,001,211 disclosing
thermal gelling cellulose ethers. Preferred matrixes in the present invention
are gelatin based.
[0034] A plasticizer is a material that increases or decreases the flexibility
or toughness of the
matrix. Glycerin, sorbitol and other materials known in the art have been used
as a plasticizer.
For,example, see U.S. Pat. No 5,264,226 disclosing a capsule having a water-
soluble cellulose
derivative as a matrix, a plasticizer, and a co-plasticizer.
[0035] In the present invention, more than one matrix material and more than
one plasticizer
material may be used to form a capsule.
[0036] Other optional ingredients known in the art, such as dyes, flavors,
fragrances,
surfactants, disintegrants, pH modifiers, and other additives may also be
blended therein. Such
materials are known in the art.
[0037] Methods for manufacturing capsules are well known in the art. For
example, pins may
be dipped into capsule compositions, and the thickness of the capsules can be
varied by varying
the temperature of the pins. For example, see U.S. Pat. No. 2,526,683, and
U.S. Pat. No.
4,817,367. Additional materials may also be incorporated in to capsule
compositions depending
on methods of manufacture, including lubricants known in the art.
[0038] Tamper resistant capsules and methods of producing tamper resistant
capsules are well
known in the art. Gelatin locking capsules are known in the art. For example,
U.S. Pat. No.
4,040,536 discloses a locking gelatin capsule.
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[0039] Capsules in the present invention may also be soft gel capsules, i.e.,
for dosing liquid
drugs, and may be filled, i.e., by injection or other means known in the art.
The composition of
soft gel capsules, methods of manufacturing, and methods of filling are known
to those of skill
in the art.
[00401 As known in the art, a proper amount of the drug is the proper amount
or type of drug
ingested in accordance with prescribing information and directions, whether by
prescription or
over the counter. Ingestion of excess drug occurs when drugs are ingested
beyond the
prescribing information and directions, which may also be an overdose.
Overdose occurs when
a drug or other chemical is ingested which causes physical damage, injury,
illness or death. An
overdose for a drug may occur following ingestion of different amount of drugs
in different
people. For example, person A ingests lOg of a drug causing an overdose,
whereas person B
ingesting lOg of the same drug does not cause an overdose.
[00411 Capsules in the present invention are utilized to encapsulate various
drugs known in the
art that present a danger when abused, or accidentally or purposefully
overdosed, for example
drugs which may cause death or serious injury to a human at a dosage of less
than 50 times the
recommended dosage, e.g., less than 20 times or less than 10 times the
recommended dosage,
including but not limited to acetylsalicylic acid, acetaminophen, vitamins,
and medications
which are psychotropic, anti-hypertensitive, anti-seizure, amphetamine, anti-
microbial,
antibiotic, anti-viral, anti-retroviral, anti-fungal, anti-depressant,
stimulants, anti-histamine, anti-
anxiety, tricyclics, tranquilizers, benzodiazepines, hypnotics, mood
stabilizers, antipsychotics, codeine,
selective serotonin reuptake inhibitors, anti-allergy, phenothiazine,
chemotherapeutics, amines,
monoamine oxidase inhibitors, anti-carcinogens, analgesics, muscle relaxants,
ergot
preparations, anti-cholinergic, anti-inflammatory, anti-gout preparations,
soporftc, hormonal
preparations, appetite suppressants, analgesics, muscle relaxants, and
opioids.
[0042) Liquid formulations of drugs are also known to those in the art. In the
present
invention, drugs in a liquid formulation may be encapsulated in capsules by
methods known to
those in the art. In the present invention, drugs in a liquid formulation may
also be encapsulated
in soft gel capsules by methods known to those in the art.
(0043] Emetics and the emetic response caused by such emetics are well known
in the art. For
example, emetics are disclosed in US Pat. No. 4,269,820. Emetics may broadly
be divided into
two classes: chemicals that product their effect by acting on the "vomiting
centre" in the
medulla, and those which act directly on the stomach itself. Certain emetics
may also act on the
medulla and the stomach, for example, emetine and cephaeline. Representative
but non limiting
emetics known in the art include methyl cephaeline, cephaelinc, emetine
hydrochloride,
psychotrine, 0-methylpsychotrine, emetamine, ipecamine, hydro-ipecamine,
ipecacunhun acid,
apomorphine, arnmoniurn carbonate, cupric sulfate, tartar emetic, zinc
sulfate, blacks mustard,
stinguinaria, copper sulfate, eucalyptole, eucalyptus oil, glycynhiza,
guaiacol, lobelia, potassium
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iodide, senega terebene, terpin hydrate, thyme, caffeine, sodium bicarbonate
salt, and mixtures
thereof.
[0044] In the present invention, an emetic is any substance tending to cause
gastric contents to
be propelled into the mouth, i.e., emesis, or vomit. An emetic dose is the
amount of emetic
required to be ingested to induce and/or cause emesis. An emetic dose causes
some of the
gastric contents to be expelled, preferably a majority of gastric contents to
be expelled, more
preferably substantially all of gastric contents to be expelled.
[0045] Preferred emetics include emetics that cause an emetic response when
administered
orally, and act upon the stomach. Preferred emetics do not produce nausea when
a dose smaller
than an emetic dose is ingested, but immediately cause emesis when an emetic
dose is ingested. \
Preferred emetics immediately cause emesis when an emetic dose is ingested,
i.e., within 1 hour
of ingesting an emetic dose, preferably within 45 minutes, more preferably
within 30 minutes,
still more preferably within 20 minutes of ingesting an emetic dose, or within
15 minutes of
consuming an emetic dose. If an overdose of drugs causes a person to lose
consciousness,
preferably emesis occurs prior to the person losing consciousness to avoid
pulmonary
aspiration. If a secondary material which blocks the emetic response, i.e.,
alcohol, is ingested
prior to, with, or after ingestion of an emetic dose, emesis preferably occurs
prior to impairment
of vomiting.
[0046] In the present invention, an emetic embedded piece is a piece of a
capsule having a
matrix, plasticizer, and at least one emetic. An emetic embedded piece may be
formed by
various methods known in the art. When manufacturing an emetic embedded piece,
a
predetermined amount of emetic is added to a matrix and plasticizer
composition so that the
piece can contain a predetermined amount of emetic (expressed in percentage
weight, or mass
per piece). This admixture of emetic, matrix, and plasticizer is then formed
into a male or
female capsule piece.
[0047] Alternatively, a capsule piece may have a sub-compartment, and an
emetic embedded
piece can be formed by adding one or more emetics to the sub-compartment. The
sub-
compartment is subsequently sealed to form an emetic embedded piece. The
emetic embedded
piece may also be formed from an admixture of matrix, plasticizer, and emetic,
in addition to an
emetic in the sub-compartment. The emetic in the admixture and the sub-
compartment may be
the same or different emetics.
[0048] In the present invention, an emetic embedded capsule is a capsule
having a matrix,
plasticizer, and at least one emetic.
[0049] Alternatively, an emetic embedded capsule may be formed with one emetic
embedded
piece and a second capsule piece. The emetic embedded piece and non-emetic
embedded piece
may consist of different matrix and plasticizer compositions so that the
pieces dissolve or
rupture in the gastric lumen at different times or different rates.
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[0050] Alternatively, an emetic embedded capsule is formed with two emetic
embedded pieces.
The emetic embedded pieces may consist of different matrix and plasticizer
compositions from
each other so that the pieces dissolve or rupture in the gastric lumen at
different rates or
different times.
[0051] Alternatively, an emetic embedded capsule can be formed when a drug is
contained
within a sub-compartment of a capsule piece, and an emetic is contained within
the main
compartment of the capsule.
[0052] Alternatively, an emetic embedded capsule can be formed when the drug
is contained
within a sub-compartment of a capsule piece formed from an admixture of a
matrix, plasticizer
and emetic, and more emetic is contained within the main compartment of the
capsule. The
emetic in the admixture may be the same or a different emetic contained within
the main,
compartment.
[0053] In the present invention, an emetic embedded piece with one matrix and
plasticizer
composition may be used with an emetic embedded piece having a different
matrix and
plasticizer composition. Difference in composition would allow for the
capsules to dissolve or
rupture in the gastric lumen at different rates or different times.
[0054] In the present invention, more than one emetic may be utilized to form
an emetic
embedded piece. In another embodiment of the present invention, an emetic
embedded capsule
may be formed with emetic embedded pieces containing different emetics.
[0055] In the present invention, it is possible to have emetic embedded
capsules to have
different colors according to the amount of emetic present. For example, an
emetic embedded
capsule impregnated with 100mg of an emetic is black; an emetic embedded
capsule
impregnated with 200mg of an emetic is blue; an emetic embedded capsule
impregnated with
300mg of an emetic is red; an emetic embedded capsule impregnated with 400mg
of an emetic
is yellow; an emetic embedded capsule impregnated with 500mg of an emetic is
white.
[0056] In another embodiment of the present invention, emetic embedded pieces
can be of
different colors according to the amount of emetic present. For example, an
emetic embedded
piece impregnated with 50mg of an emetic is black; an emetic embedded piece
impregnated
with 100mg of an emetic is blue; an emetic embedded piece impregnated with
150mg of an
emetic is red; an emetic embedded piece impregnated with 200mg of an emetic is
yellow; an
emetic embedded piece impregnated with 250mg of an emetic is white. Thus an
emetic
embedded capsule containing 150 mg of an emetic would be a black and a:blue
emetic
embedded piece (50mg in a black emetic embedded piece, and 100mg in a blue
emetic
embedded piece); an emetic embedded capsule containing 300 mg of an emetic
would be a
black and a white emetic embedded piece (50mg in a black emetic embedded
piece, and 250mg
in a white emetic embedded piece), or two red emetic embedded pieces (150mg in
two red
emetic embedded pieces).
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[0057] In another embodiment of the present invention, emetic embedded pieces
and capsules
can be different colors depending on the emetic or combination of emetics
embedded within the
piece or capsule. For example, an emetic embedded piece containing zinc
sulfate is green; an
emetic embedded piece containing apomorphine is yellow; an emetic embedded
piece
containing zinc sulfate and apomorphine is red; an emetic embedded capsule
formed with an
apomrphine embedded piece and a zinc sulfate embedded piece has a yellow and a
green emetic
embedded piece.
[0058] In one embodiment of the present invention, a drug, optionally along
with excipients,
such as fillers, binders, disintegration agents, lubricants, colorants, or
other conventional
adjuvants, is packaged into the emetic embedded capsule.
[0059] Many drugs known in the art are provided in tablet dosage forms
comprising some
particulated forms of ingredients. It is known in the art that tablets may
also contain excipients,
such as fillers, binders, disintegration agents, lubricants, colorants, or
other conventional
adjuvants.
[0060] In one embodiment of the present invention, a tablet is "ground up"
along with any
excipients in the tablet, such as fillers, binders, disintegration agents,
lubricants, colorants, or
other conventional adjuvants, and is packaged into the emetic embedded
capsule.
[0061] The present invention can also be used to encapsulate a tablet,
capsule, or soft gel
capsule containing one or more drugs and excipients, such that the drug is
first contained within
a non-emetic embedded capsule or tablet, and then the non-emetic embedded
capsule or tablet is
encapsulated within an emetic embedded capsule. The matrix and plasticizer
selected to form
the emetic embedded capsule can be a different composition from the matrix and
plasticizer that
actually encapsulates the tablet or capsule containing the drugs and
excipients so that the
differences in composition would allow for the capsules to dissolve or rupture
in the gastric
lumen at different rates or different times.
[0062] In the present invention, the amount of drug administered to a patient
can be
independent of the amount of the emetic embedded within the capsule. One of
ordinary skill in
the art can readily determine the amount of drug needed for a particular
treatment. One of
ordinary skill in the art can also readily determine the amount of a drug a
patient can ingest
without an overdose. One of ordinary skill in the art can also determine the
kind and amount of
a particular emetic or combination of emetics a person needs to ingest to
induce emesis. Thus,
one of ordinary skill can select emetic embedded pieces or capsules to provide
to a patient, such
that the patient would ingest a sufficient amount of emetic to induce emesis
before ingesting, or
concurrently ingesting, a sufficient amount of drug to create an overdose.
[0063] When orally administered to a patient, the emetic embedded capsule
passes to the
stomach where the emetic embedded capsule dissolves or ruptures, and the
emetic is released
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into the stomach. If an emetic dose is ingested, emesis should occur before
any significant
amount of drug is released or absorbed so that the drug is expelled from the
body by emesis.
[0064] The amount of the emetic in an individual emetic embedded capsule is
such that the
amount of emetic present will not induce emesis. When an appropriate amount of
the drug is
ingested, no emetic response is provoked. However, when excess drugs are
ingested, emesis
occurs.
[0065] The present invention is intended to provide flexibility to healthcare
professionals, such
as doctors and pharmacists, in prescribing and dispensing a wide variety of
drugs to individual
patients.
[0066] In the present invention, the consumption of a number of emetic
embedded capsules
does not produce nausea or retching. However, consumption of more emetic
embedded
capsules may cause nausea, retching and emesis. A preferred emetic does not
cause nausea or
retching prior to ingesting an emetic dose.
[0067] An effective amount of emetic to be embedded in an emetic embedded
capsule can be
calculated by various methods.
[0068] In one method, a drug has a specific dosage form and amount (i.e., same
drugs have
different dosage amounts in tablet or capsule forms). The drug also has a
level of overdose or
toxicity. It can be readily determined how many tablets or capsules containing
a specific
amount of drug will need to be ingested before the drug causes an overdose or
toxic effect in a
person. It can also be readily determined how much emetic is necessary to
induce emesis in the
same person. A capsule impregnated with a specific mass or amount of emetic is
then selected
from a group of emetic embedded capsules so that the amount of emetic ingested
would cause
emesis before a person is able to ingest sufficient quantity of drug to cause
overdose, or emesis
would occur shortly after the person ingests a sufficient quantity of drug to
cause overdose.
[0069] For example, a drug is prescribed in 50mg dosages contained in a tablet
or capsule, and
causes an overdose at 10mg/kg. A 70 kg person would thus need to ingest 700
mg, or 14 tablets
before an overdose occurs. An emetic induces a response in a person when 5
grams are
ingested. Thus, at least 5 grams of emetic would need to be contained in 14
capsules. A
pharmacist receives the prescription and recognizes that the person is a
suicide risk and chooses
to pack the drug into an emetic embedded capsule. The pharmacist has a choice
of emetic
embedded capsules impregnated with 100mg, 200mg, 300mg, 400mg, or 500mg of
emetic per
capsule. The pharmacist would select a 400mg emetic embedded capsule, and pack
the drug the
400mg emetic embedded capsule so that if 14 pills are ingested, 5.6 grams of
emetic would be
ingested to induce emesis in the 70 kg person. Alternatively, a pharmacist
could select the 500
mg emetic embedded capsule so that ingestion of 10 of the pills would induce
emesis.
[0070] In another method, a drug has a specific dosage form and amount (i.e.,
same drugs have
different dosage amounts in tablet or capsule forms). The drug also has a
specific level of
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overdose or toxicity. It can be readily determined how many tablets or
capsules containing a
specific amount of drug will need to be ingested before the drug causes an
overdose or toxic
effect in a person. It can also be readily determined how much emetic is
necessary to induce
emesis in the same person. A capsule impregnated with a type or mixture of
emetic is then
selected from a group of emetic embedded capsules so that the type or mixture
of emetic
ingested would cause emesis before a person is able to ingest sufficient
quantity of drug to
cause overdose, or emesis would occur shortly after the person ingests a
sufficient quantity of
drug to cause overdose.
[0071] For example, a drug is prescribed in 50mg dosages contained in tablets
or capsules, and
causes an overdose at 10mg/kg. A 70 kg person would need to ingest 700 mg, or
14 tablets
before an overdose occurs. Thus, an emetic would need to be effective when at
least 14
capsules are ingested. A pharmacist receives the prescription and recognizes
that the person is a
suicide risk, or has small children, or is confused about his dosage, and
chooses to pack the drug
into an emetic embedded capsule. The pharmacist has a choice of emetic
embedded capsules
impregnated with different emetics. Three different emetic embedded capsules
containing the
same mass of emetic are available for encapsulating the drug: a first emetic
embedded capsule
containing a first emetic that induces a response in a person when 3 grams are
ingested; a
second emetic embedded capsule containing a second emetic that induces a
response in a person
when 5 grams are ingested; and a third emetic embedded capsule containing a
third emetic that
induces a response in a person when 9 grams are ingested. Each emetic embedded
capsule only
contains 400 mg of the emetic. The drug dispenser would select the first or
second emetic
embedded capsules so that if 14 pills are ingested, 5.6 grams of the first
emetic would be
ingested to induce emesis in the 70 kg person, or 5.6 grams of the second
emetic would be
ingested to induce emesis in the 70 kg person.
[0072] In another method, a drug has been prescribed in a unit dose per period
of time, e.g.,
one capsule or tablet once a day, or X number of capsules or tablets per
period of time.
Consumption of Y tablets or capsules during the same period would result in an
overdose of the
drug, causing a risk of death or serious harm to the patient. Therefore, an
emetic embedded
capsule is selected such that the emetic embedded capsule contains enough
emetic to induce
emesis if a number of capsules approaching the overdose number (Y) capsules
were ingested.
The appropriate emetic embedded capsule would therefore contain at least 1/Y
but less than 1/X
of the emetic dose required for an emetic response, or within the range of 1/X
to 1/Y.
[0073] For example, a drug is prescribed as one tablet at a time. A pharmacist
recognizes that
an overdose could occur if two tablets are ingested. Accordingly, the
pharmacist selects an
emetic embedded capsule that contains at least 1/2 of an emetic dose, but less
than 1 emetic
dose.
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[0074] For example, a drug is prescribed as three tablets at a time. A
pharmacist recognizes
that an overdose would occur if four tablets are ingested. Accordingly, the
pharmacist selects
an emetic embedded capsule that contains at least 1/4 of an emetic dose, but
less than 1/3 of an
emetic dose.
[0075] For example, a drug is prescribed as three tablets at a time. A
pharmacist recognizes
that an overdose would occur if six tablets are ingested. Accordingly, the
pharmacist selects an
emetic embedded capsule that contains from at least 1/6 to less than 1/3 of an
emetic dose so
thatif 3 embedded capsules are ingested, emesis does not occur, but if an
emetic embedded
capsule having 1/4 of an emetic dose is selected and 4 or more embedded
capsules are ingested,
emesis would occur and if an emetic embedded capsule having an 1/5 of an
emetic dose is
selected and five or more embedded capsules are ingested, emesis would occur,
and if an emetic
embedded capsule having an 1/6 of an emetic dose is selected and 6 or more
embedded capsules
are ingested, emesis would occur.
[0076] In another method, a drug may contain more than one ingredient that may
cause an
overdose. The ingredient that is most toxic or potential for overdose should
be used in selecting
the particular emetic embedded capsule.
[0077] In the present invention, it may be convenient for a pharmacist or
other health care
professional to have one or a series of tables for easy consultation when
selecting a particular
emetic embedded capsule to encapsulate a drug. The table would identify the
emetic, or
combination of emetic, and an emetic dosage according to a person's weight, or
other
characteristic affecting the emetic dosage. Additional tables may also include
particular
emetics, or combination of emetics, and an emetic dosage according to a
person's weight or
other characteristic affecting the emetic dosage, and particular drugs.
[0078] In another embodiment of the present invention, an emetic composition
may be spray
coated onto a one or more drugs admixed, or a tablet, capsule, or soft gel
containing one or
more drugs by any number of methods of spray coating known in the art. The
emetic
composition contains an emetic and matrix such that when the composition is
spray coated onto
the drug, tablet, capsule or soft gel. Emetic compositions suitable or
spraying have one or more
emetics, matrixes, and solvents in which the emetics or matrixes are dissolved
or suspended in.
After the emetic composition is sprayed onto the capsule, the solvent
evaporates, leaving behind
the matrix and emetic coated onto the capsule. Solvents are well known in the
art, and may
include plasticizers and/or organic solvents.
[0079] It may be appreciated that certain emetics may be toxic in and of
themselves. Although
one object of the present invention is to prevent accidental or intentional
overdose of drugs, the
compositions provided herein should also be safe to ingest on a regular basis,
i.e., hourly, four
times a day, daily, weekly, in accordance with a doctor's prescription, or in
accordance with the
proper dosage. Accordingly, all of the forgoing compositions and emetics may
also be
11
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combined with one or more inert materials known in the art that are
substantially inert to a
gastrointestinal environment such that when the combination of the emetic
chemical and inert
material is ingested and passed along the gastrointestinal tract, emesis can
be induced when the
emetic embedded capsules are ingested in sufficient quantity. However when the
emetic
embedded capsule is ingested in appropriate quantities, the emetic is not
absorbed into the body,
but will be passed through the gastrointestinal tract and eliminated from the
body. Inert
materials suitable to be added to the present invention are known in the art.
For example, see
U.S. Pat. No. 4,529,583.
Example
[0080] Carrageenan is a polysaccharide hydrocolloid which may be extracted
from seaweed.
Several forms of Carrageenan exist, including the kappa, iota, and lambda
forms. Kappa-
carregeenan is known to form gels in the presence of potassium cations. Iota-
carregeenan is
known to form gels in the presence of calcium cations. A carregeen capsule may
be prepared
by the following steps:
[0081] 1. Dispersing kappa-carrageenan or a blend of kappa-carrageenan and
iota-
carrageenantgelling salt/mannan gum/xanthan gum (if these materials are
present) at ambient or
at least slightly elevated temperature (higher temperatures, of course,
usually being
advantageous in the physical dissolution of most materials) in a plasticizer
(or mixture of
plasticizers);
[0082] 2. An aqueous solution is prepared by dissolving other additives (e.g.,
maltodextrin,
gum arabic and protein) in water (preferably at about ambient temperature, but
some slight
elevation or reduction in temperature may be used);
[0083] 3. The aqueous solution is added to the kappa-carrageenan/plasticizer
mixture to form a
working composition.
[0084] 4. The working composition is heated, preferably with stirring to at
above 130 F to
below the boiling point of the working mixture, preferably between 135 and 210
F, more
preferably between about 160 to 180 F.
[0085] 5. An emetic is added to the working composition; and
[0086] 6. The heated working composition containing the emetic can then be
transferred or
introduced for processing to a conventional gelatin encapsulation machine
(films are formed by
casting the solution on cooled rotating (e.g., metal such as steel) drums, the
films are fed
through a series of rollers to counter-rotating dies which form, cut and fill
capsules of various
sizes.
[0087] The following working compositions can be prepared, the ingredients of
the
compositions being expressed in percentages by weight:
Composition 1
Kappa-carrageenan 4%
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Maltitol syrup 30%
Sorbitol solution 2.5%
Deionized water 63.5%
Composition 2
Kappa-carrageenan 4%
Maltitol Syrup 20%
Glycerin 11%
Deionized water 65%
[0088] An amount of emetic may be added to the working composition so that a
capsule piece
may be formed containing .1mg to 500 mg of emetic per piece.
Example 2
[0089] Acetaminophen is a common prescription and over the counter drug
frequently abused,
causing an overdose resulting in hepatic toxicity and death. Hepatic toxicity
may occur
following ingestion of 7.5 grams of acetaminophen, and fatalities may occur
following ingestion
of 15 grams of acetaminophen. Acetaminophen is available in various dosages,
for example, 80,
325, 500, and 650 milligrams per tablet or capsule. Different emetic embedded
capsules may be
selected to encapsulate the acetaminophen depending on the dosage. For
example, ninety four
80 mg acetaminophen tablets would need to be ingested before an overdose would
occur; fifteen
500 mg acetaminophen tablets would need to be ingested before an overdose
would occur;
twelve 650 mg acetaminophen tablets would need to be ingested before an
overdose would
occur. Accordingly, when encapsulating a 650 mg dose of acetaminophen with an
emetic
embedded capsule, the emetic embedded capsule should be selected from a group
that would
induce emesis before twelve capsules are ingested. When encapsulating a 500 mg
dose of
acetaminophen in an emetic embedded capsule, the emetic embedded capsule
should be selected
from a group that would induce emesis before fifteen capsules are ingested.
When
encapsulating a 80 mg dose of acetaminophen with an emetic embedded capsule,
the emetic
embedded capsule should be selected form a group that would induce emesis
before ninety four
capsules are ingested.
[0090] For example, if acetaminophen is prescribed in 325 mg dosages, an
overdose by
consumption of the acetaminophen would therefore occur when at least twenty-
three 325mg
tablets or capsules are ingested. An emetic embedded capsule embedded with an
emetic which
causes emesis when 5 grams of emetic is ingested is selected to encapsulate
the acetaminophen.
The emetic embedded capsule would therefore need to contain at least 217mg of
an emetic so
that when 7.5 grams of acetaminophen is ingested (23 pills ingested), 5 grams
of emetic have
also been ingested to induce emesis. Emesis would occur before substantial
amount of
acetaminophen is released in the stomach and absorbed by the body.
Example 2A
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[0091] A pharmacy is able to purchase and keep in stock the embodiment shown
in figure 1,
i.e., emetic embedded pieces wherein a predetermined amount of emetic is
contained within a
capsule piece, and keep a wide variety in stock. A pharmacist has the choice
of an emetic
embedded piece containing 100mg, 150mg, 200mg, 250mg, and 300mg of emetic.
When a
prescription for a dose of 325 mg of acetaminophen is presented, the
pharmacist has the option
of selecting emetic embedded pieces having 250mg, or 300mg of emetic to
encapsulate the
acetaminophen. The pharmacist adds the acetaminophen to the emetic embedded
piece and
seals the capsule with a second capsule piece. Alternatively, the pharmacist
can select the
100mg and 150mg emetic embedded pieces to encapsulate 325 mg of acetaminophen
and form
the emetic embedded capsule.
Example 213
[0092] An acetaminophen manufacturer can encapsulate 325rng acetaminophen
dosages within
an emetic embedded capsule and market the same under a label "contains
emetics."
Example 3
[0093] Alprazolam (marketed as XANAX by Pfizer) is a frequently abused
prescription drug
and is dispensed in 2mg tablets. A pharmacist has the option of grinding up
the tablet, and
encapsulating the powder in an emetic encapsulated capsule, or encapsulating
the whole tablet
inside of an emetic encapsulated capsule.
Example 4
[0094] Fluoxetine hydrochloride (marketed as PROZACO and SARAFEM by Eli Lily
and
Company) is a frequently abused prescription drug and may be prescribed in
10mg tablets. It is
reported that ingestion of 520 mg of fluoxetine hydrochloride has caused
death, but there are
other side effects that occur much sooner. Due to the toxicity of a low dosage
of fluoxetine
hydrochloride which may be substantially smaller than a lethal dose, the
selected emetic
embedded capsule induces emesis with the ingestion of only a few capsules,
i.e., ingesting 4, 10,
20, 25, 30, or 40 capsules would induce emesis. Because fluoxetine
hydrochloride is a widely
prescribed drug, capsule pieces are manufactured with fluoxetine hydrochloride
contained
within the piece's sub compartment. A pharmacist then creates an emetic
embedded capsule by
adding an emetic to the capsule piece having the sub-compartment containing
fluoxetine
hydrochloride, and then sealing the emetic embedded capsule with a non-emetic
embedded
piece, an emetic embedded piece, or another piece having fluoxetine
hydrochloride contained
within a sub-compartment.
Example 5
TM
[0095] Diazepam (marketed as VALIUM by Roche Pharmaceuticals) is a
benzodiazepine
derivative which is frequently abused. Oral LD 50 of diazepam is 720 mg/kg in
mice, and 1240
mg/kg in rats. Depending on severity of the condition, VALIUM may be
prescribed 10mg 4
times per day. VALIUM is dispensed in 2mg, 5mg, and 10mg tablets. A pharmacist
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recognizes that the patient has a history of drug abuse, and chooses to pack
the diazepam in an
emetic encapsulated capsule. The pharmacist also recognizes that the patient
is prone to
tampering with capsules, so selects an emetic embedded capsule with a tamper
resistant lock.
Example 6
[0096] Hydrocodone bitartrate (marketed as VICODIN , VICODIN ES , and VICODIN
HP by Abbott Laboratories) is a frequently abused opioid analgesic and
antitussive.
Hydrocodone bitartrate is frequently administered with acetaminophen (i.e.,
VICODIN
contains 5 mg hydrocodone bitartrate and 500 mg acetaminophen per tablet;
VICODIN ES
contains 7.5 mg hydrocodone bitartrate and 750 mg acetaminophen per tablet;
and VICODIN
HP contains 10 mg hydrocodone bitartrate and 660 mg acetaminophen per
tablet).
Hydrocodone bitartrate and acetaminophen can cause toxicity or death. Patients
are frequently
counseled not to take a double dosage of VICODIN due to the toxicity of
hydrocodone
bitartrate. A health care professional would therefore be more concerned with
the hydrocodone
bitartrate because it would cause the toxicity or death rather than the
acetaminophen.
[0097] Zinc sulfate heptahydrate causes emesis when .6 grams are ingested. An
emetic
embedded capsule should contain between .3 and .6 grams of zinc sulfate so
that when a double
dose of VICODIN is ingested, emesis occurs.
Example 7
[0098] Triazolm (marketed as HALCION by Pharmacia & Upjohn) is a hypotonic
agent
which is abused. Manifestations of overdose may occur after ingestion of 2 mg.
HALCION
is dispensed as .125 mg and .25 mg tablets. Because of the potency of the
triazolm and the
ability of an individual to ingest more than 4 pills at a time (four .25 mg
tablets is 2mg of
Triazolm, which could produce an overdose), an emetic embedded capsule should
contain
sufficient emetic to induce emesis as soon as more than 2 emetic embedded
capsules are
ingested. Thus, an emetic embedded capsule containing between .3 and .6 grams
of zinc sulfate
is used to encapsulate triazolm so that consumption of 1 capsule will not
cause emesis, but
consumption of 2 capsules will cause emesis.
Example 8
[0099] Methylphenidate hydrochloride (marketed as CONCERTA by McNiel Consumer
Healthcare) is a central nervous system stimulant that is frequently abused.
CONCERTA
tablets uses osmotic pressure to deliver methylphenidate hydrochloride at a
controlled rate. The
CONCERTA tablet resembles a conventional tablet, comprising an osmotically
active trilayer
core surrounded by a semipermeable membrane with an immediate-release drug
overcoat. The
trilayer is composed of two drug layers containing the drug and excipients,
and a push layer
containing osmotically active components. There is a precision laser drilled
orifice on the drug
layer end of the tablet. Following ingestion, the drug overcoat dissolves,
providing an initial
dose or methylphenidate. Water permeates through the membrane into the tablet
core, and as
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osmotically active polymer excipients expand, methylphenidate is released
through the orifice.
The CONCERTA tablet contains biologically inert components which remain intact
during
gastrointestinal transit and are eliminate in the stool, along with insoluble
core components.
Accordingly, a CONCERTA tablet cannot be ground up and encapsulated within an
emetic
embedded capsule. However, a pharmacist is able to select emetic embedded
capsules having a
sub-compartment containing an emetic (as shown in Fig. 1), and encapsulating
the
CONCERTA tablet to create an emetic embedded capsule containing an
appropriate amount
of emetic.
(001001Alternatively, manufacturers of CONCERTA can elect to encapsulate
CONCERTA
within the sub-compartment of a capsule piece so that a pharmacist will be
able to encapsulate
an appropriate amount of emetic in the capsule's main compartment. This allows
the pharmacist
the flexibility to create custom emetic doses for individuals. An appropriate
amount of emetic
is a specific mass that would not cause emesis when the drug is ingested in
proper quantities,
and the number of emetic embedded capsules ingested to induce emesis is less
than the number
of emetic embedded capsules ingested to cause a drug overdose.
Example 9
(00101]Bupropion hydrochloride (marketed as WELLBUTRIN4i, and ZYBAN 11 by
GlaxoSmithKline) is an antidepressant frequently abused. WELLBUTRING is
dispensed as 75
mg or 100 mg tablets, and ZYBAN0 is dispensed as 150mg tablets. In populations
of
individuals experienced with drugs of abuse, a single dose of 400mg of
WELLBUTRIN
produced mild amphetamine-like activity. Bupropion is associated with seizures
in
approximately .4% of patients treated at doses up to 450 mg/day, which may
exceed that of
other marketed antidepressants by as much as fourfold. The estimated seizure
incidence for
WELLBUTRIN increases almost 10-fold between 450 mg/day and 600 mg/day. It is
recommended that to reduce the risk of seizure, a single dose of WELLBUTRIN or
ZYBAN not
exceed 150mg. A pharmacist thus packets ZYBAN into an emetic embedded capsule
or emetic
embedded piece which would cause emesis when two 150mg doses are consumed to
avoid
amphetamine-like activity and reduce the risk of seizure. A pharmacist may
also packet 100 mg
WELLBUTR1N tablets in an emetic embedded capsule which would cause emesis when
4
tablets are consumed to reduce the risk of seizure, however, will not cause
emesis when 2
tablets are consumed which may cause amphetamine-like activity.
[00102]The matters set here are offered by way of illustration only and not as
limitations.
While particular embodiments have been shown and described, the scope of the
claims
should not be limited by the particular embodiments set forth. The claims
should be
given the broadest interpretation consistent with the description as a whole.
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