WO2006138278A1 - Capsule contenant un émétique - Google Patents

Capsule contenant un émétique Download PDF

Info

Publication number
WO2006138278A1
WO2006138278A1 PCT/US2006/022939 US2006022939W WO2006138278A1 WO 2006138278 A1 WO2006138278 A1 WO 2006138278A1 US 2006022939 W US2006022939 W US 2006022939W WO 2006138278 A1 WO2006138278 A1 WO 2006138278A1
Authority
WO
WIPO (PCT)
Prior art keywords
emetic
drug
capsule
embedded
encapsulated
Prior art date
Application number
PCT/US2006/022939
Other languages
English (en)
Inventor
Paul Rosenberg
Original Assignee
Paul Rosenberg
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Paul Rosenberg filed Critical Paul Rosenberg
Priority to CA2612044A priority Critical patent/CA2612044C/fr
Priority to JP2008517007A priority patent/JP2008543851A/ja
Priority to EP06773005A priority patent/EP1893183A4/fr
Publication of WO2006138278A1 publication Critical patent/WO2006138278A1/fr
Priority to US12/001,877 priority patent/US9060950B2/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4816—Wall or shell material
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4883—Capsule finishing, e.g. dyeing, aromatising, polishing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system

Definitions

  • AU 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.
  • 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.
  • 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.
  • an emetic embedded piece is formed from an admixture comprising a matrix, a plasticizer, and an emetic.
  • an 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.
  • 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.
  • 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.
  • a drug is encapsulated within an emetic embedded capsule to form an emetic encapsulated drug.
  • a central and/or gastric emetic is used as an emetic.
  • an emetic having both central and gastric effect is used in an emetic embedded capsule or an emetic embedded piece.
  • 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.
  • different color emetic embedded capsules or pieces may signify different amounts of emetics contained within an emetic embedded capsule or piece.
  • 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.
  • different color emetic embedded capsules or pieces may signify different types of emetic chemicals present in an emetic embedded capsule or piece.
  • a laxative may be substituted for the emetic.
  • the capsules may contain fragrances and flavors.
  • 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.
  • Fig. 1 is an emetic embedded capsule in accordance with the present invention.
  • 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.
  • the two pieces each have an outer circumference, a thickness, and an inner circumference.
  • the inner circumference 6 A of the female piece 6 is slightly smaller than the outer circumference 4A of the male piece 4 so that the male piece engages the female piece to form a seal to prevent leakage of the contents of the capsule.
  • the two pieces may be the same or identical size having means to engage one another, such means being known in the art.
  • 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.
  • 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.
  • Capsules and capsule pieces typically contain a matrix and a plasticizer.
  • 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.
  • 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.
  • 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.
  • more than one matrix material and more than one plasticizer material may be used to form a capsule.
  • capsules are well known in the art.
  • pins may be dipped into capsule compositions, and the thickness of the capsules can be varied by varying the temperature of the pins.
  • the temperature of the pins 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.
  • 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.
  • 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 1Og of a drug causing an overdose, whereas person B ingesting 1Og of the same drug does not cause an overdose.
  • 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, antianxiety, tricyclics, tranquilizers, benzodiazepines, hypnotics, mood stabilizers, codeine, selective serotonin reuptake inhibitors, anti-allergy, phenothiazine, chemotherapeutics, amines
  • Liquid formulations of drugs are also known to those in the art.
  • drugs in a liquid formulation may be encapsulated in capsules by methods known to those in the art.
  • drugs in a liquid formulation may also be encapsulated in soft gel capsules by methods known to those in the art.
  • Emetics and the emetic response caused by such emetics are well known in the art.
  • 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.
  • emetics known in the art include methyl cephaeline, cephaeline, emetine hydrochloride, psychotrine, O-methylpsychotrine, emetamine, ipecamine, hydro-ipecamine, ipecacunhun acid, apomorphine, ammonium carbonate, cupric sulfate, tartar emetic, zinc sulfate, blacks mustard, sanguinaria, copper sulfate, eucalyptole, eucalyptus oil, glycynhiza, guaiacol, lobelia, potassium iodide, senega terebene, terpin hydrate, thyme, caffeine, sodium bicarbonate salt, and mixtures thereof.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • an emetic embedded capsule is a capsule having a matrix, plasticizer, and at least one emetic.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • emetic embedded piece more than one emetic may be utilized to form an emetic embedded piece.
  • an emetic embedded capsule may be formed with emetic embedded pieces containing different emetics.
  • an emetic embedded capsule impregnated with lOOmg 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.
  • emetic embedded pieces can be of different colors according to the amount of emetic present.
  • an emetic embedded piece impregnated with 50mg of an emetic is black; an emetic embedded piece impregnated with lOOmg 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.
  • 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 lOOmg 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).
  • 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.
  • 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.
  • excipients such as fillers, binders, disintegration agents, lubricants, colorants, or other conventional adjuvants
  • tablets may also contain excipients, such as fillers, binders, disintegration agents, lubricants, colorants, or other conventional adjuvants.
  • 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.
  • excipients such as fillers, binders, disintegration agents, lubricants, colorants, or other conventional adjuvants
  • 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.
  • 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 ordinaiy 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.
  • emetic embedded pieces or capsules can be selected 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.
  • the emetic embedded capsule passes to the stomach where the emetic embedded capsule dissolves or ruptures, and the emetic is released 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.
  • the amount of the emetic in an individual emetic embedded capsule is such that the amount of emetic present will not induce emesis.
  • an appropriate amount of the drug is ingested, no emetic response is provoked. However, when excess drugs are ingested, emesis occurs.
  • 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.
  • the consumption of a number of emetic embedded capsules does not produce nausea or retching.
  • 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.
  • An effective amount of emetic to be embedded in an emetic embedded capsule can be calculated by various methods.
  • 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.
  • 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.
  • 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 lOOmg, 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.
  • a pharmacist could select the 500 mg emetic embedded capsule so that ingestion of 10 of the pills would induce emesis.
  • 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 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • compositions and emetics may also be 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.
  • inert materials suitable to be added to the present invention are known in the art. For example, see
  • Carrageenan is a polysaccharide hydrocolloid which may be extracted from seaweed.
  • Carrageenan Several forms 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:
  • 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);
  • additives e.g., maltodextrin, gum arabic and protein
  • the aqueous solution is added to the kappa-carrageenan/plasticizer mixture to form a working composition.
  • 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.
  • 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.
  • 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.
  • compositions [0087] The following working compositions can be prepared, the ingredients of the compositions being expressed in percentages by weight:
  • An amount of emetic may be added to the working composition so that a capsule piece may be formed containing .lmg to 500 mg of emetic per piece.
  • Example 2
  • 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.
  • the emetic embedded capsule should be selected from a group that would induce emesis before twelve capsules are ingested.
  • the emetic embedded capsule 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.
  • 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.
  • Example 2A 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 lOOmg, 150mg, 200mg, 250mg, and 300mg of emetic.
  • 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.
  • the pharmacist can select the lOOmg and 150mg emetic embedded pieces to encapsulate 325 mg of acetaminophen and form the emetic embedded capsule.
  • Example 2B
  • An acetaminophen manufacturer can encapsulate 325mg acetaminophen dosages within an emetic embedded capsule and market the same under a label "contains emetics.”
  • Example 3
  • 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.
  • XANAX® XANAX®
  • Fluoxetine hydrochloride (marketed as PROZAC® and SARAFEM® by Eli Lily and Company) is a frequently abused prescription drug and may be prescribed in lOmg 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.
  • 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
  • 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 lOmg 4 times per day. VALIUM is dispensed in 2mg, 5mg, and 10 mg tablets. A pharmacist 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.
  • 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).
  • 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
  • VICODIN HP® contains 10 mg hydrocodone bitartrate and 660 mg
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 CONCERT A® 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 CONCERT A® tablet to create an emetic embedded capsule containing an appropriate amount of emetic.
  • CONCERTA® manufacturers of CONCERTA® can elect to encapsulate CONCERT A® 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.
  • Bupropion hydrochloride (marketed as WELLBUTRIN®, and ZYB AN® by GlaxoSmithKline) is an antidepressant frequently abused. WELLBUTRIN® is dispensed as 75 mg or 100 mg tablets, and ZYB AN® 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.
  • 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 WELLBUTRIN 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.

Landscapes

  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des capsules qui contiennent un émétique et qui peuvent encapsuler un médicament, la quantité d'émétique et la quantité de médicament étant telles que le nombre de capsules à ingérer pour provoquer un vomissement est inférieur au nombre de capsules qu'il faut ingérer pour être intoxiqué par le médicament. De cette manière, si une personne prend une dose excessive du médicament encapsulé dans l'émétique, elle vomira avant que le médicament soit absorbé par l'organisme.
PCT/US2006/022939 2005-06-13 2006-06-13 Capsule contenant un émétique WO2006138278A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CA2612044A CA2612044C (fr) 2005-06-13 2006-06-13 Capsule contenant un emetique
JP2008517007A JP2008543851A (ja) 2005-06-13 2006-06-13 催吐剤封入カプセル
EP06773005A EP1893183A4 (fr) 2005-06-13 2006-06-13 Capsule contenant un émétique
US12/001,877 US9060950B2 (en) 2005-06-13 2007-12-13 Emetic embedded capsule

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US69002305P 2005-06-13 2005-06-13
US60/690,023 2005-06-13

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US12/001,877 Continuation US9060950B2 (en) 2005-06-13 2007-12-13 Emetic embedded capsule

Publications (1)

Publication Number Publication Date
WO2006138278A1 true WO2006138278A1 (fr) 2006-12-28

Family

ID=37570767

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2006/022939 WO2006138278A1 (fr) 2005-06-13 2006-06-13 Capsule contenant un émétique

Country Status (4)

Country Link
EP (1) EP1893183A4 (fr)
JP (1) JP2008543851A (fr)
CA (1) CA2612044C (fr)
WO (1) WO2006138278A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9492444B2 (en) 2013-12-17 2016-11-15 Pharmaceutical Manufacturing Research Services, Inc. Extruded extended release abuse deterrent pill
US9522119B2 (en) 2014-07-15 2016-12-20 Isa Odidi Compositions and methods for reducing overdose
US9707184B2 (en) 2014-07-17 2017-07-18 Pharmaceutical Manufacturing Research Services, Inc. Immediate release abuse deterrent liquid fill dosage form
US10172797B2 (en) 2013-12-17 2019-01-08 Pharmaceutical Manufacturing Research Services, Inc. Extruded extended release abuse deterrent pill
US10195153B2 (en) 2013-08-12 2019-02-05 Pharmaceutical Manufacturing Research Services, Inc. Extruded immediate release abuse deterrent pill
US10959958B2 (en) 2014-10-20 2021-03-30 Pharmaceutical Manufacturing Research Services, Inc. Extended release abuse deterrent liquid fill dosage form

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4175119A (en) * 1978-01-11 1979-11-20 Porter Garry L Composition and method to prevent accidental and intentional overdosage with psychoactive drugs
US4269820A (en) * 1977-02-11 1981-05-26 Imperial Chemical Industries Limited Safeguarded toxic chemical compositions containing effective emesis-inducing S-triazolo-[1,5-α]pyrimidine derivatives
US5756123A (en) * 1994-12-01 1998-05-26 Japan Elanco Co., Ltd. Capsule shell

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1428361A (en) * 1972-02-15 1976-03-17 Grant A Safeguarded medicinal compositions
US4529583A (en) * 1983-03-07 1985-07-16 Clear Lake Development Group Composition and method of immobilizing emetics and method of treating human beings with emetics
GB9704524D0 (en) * 1997-03-05 1997-04-23 Smithkline Beecham Plc Composition
US20030170181A1 (en) * 1999-04-06 2003-09-11 Midha Kamal K. Method for preventing abuse of methylphenidate
AU2002339378A1 (en) * 2001-05-22 2002-12-03 Euro-Celtique Compartmentalized dosage form
US20030044458A1 (en) * 2001-08-06 2003-03-06 Curtis Wright Oral dosage form comprising a therapeutic agent and an adverse-effect agent
US7524515B2 (en) * 2003-01-10 2009-04-28 Mutual Pharmaceuticals, Inc. Pharmaceutical safety dosage forms
CA2536816A1 (fr) * 2003-08-12 2005-03-03 Endo Pharmaceuticals, Inc. Procede permettant d'empecher l'abus d'opioides par combinaison avec une formulation non liberable d'emetique

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4269820A (en) * 1977-02-11 1981-05-26 Imperial Chemical Industries Limited Safeguarded toxic chemical compositions containing effective emesis-inducing S-triazolo-[1,5-α]pyrimidine derivatives
US4175119A (en) * 1978-01-11 1979-11-20 Porter Garry L Composition and method to prevent accidental and intentional overdosage with psychoactive drugs
US5756123A (en) * 1994-12-01 1998-05-26 Japan Elanco Co., Ltd. Capsule shell

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP1893183A4 *

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10195153B2 (en) 2013-08-12 2019-02-05 Pharmaceutical Manufacturing Research Services, Inc. Extruded immediate release abuse deterrent pill
US10639281B2 (en) 2013-08-12 2020-05-05 Pharmaceutical Manufacturing Research Services, Inc. Extruded immediate release abuse deterrent pill
US10172797B2 (en) 2013-12-17 2019-01-08 Pharmaceutical Manufacturing Research Services, Inc. Extruded extended release abuse deterrent pill
US9492444B2 (en) 2013-12-17 2016-11-15 Pharmaceutical Manufacturing Research Services, Inc. Extruded extended release abuse deterrent pill
US10792254B2 (en) 2013-12-17 2020-10-06 Pharmaceutical Manufacturing Research Services, Inc. Extruded extended release abuse deterrent pill
US9700516B2 (en) 2014-07-15 2017-07-11 Isa Odidi Compositions and methods for reducing overdose
US9801939B2 (en) 2014-07-15 2017-10-31 Isa Odidi Compositions and methods for reducing overdose
US9700515B2 (en) 2014-07-15 2017-07-11 Isa Odidi Compositions and methods for reducing overdose
US10293046B2 (en) 2014-07-15 2019-05-21 Intellipharmaceutics Corp. Compositions and methods for reducing overdose
US9522119B2 (en) 2014-07-15 2016-12-20 Isa Odidi Compositions and methods for reducing overdose
US10653776B2 (en) 2014-07-15 2020-05-19 Intellipharmaceutics Corp. Compositions and methods for reducing overdose
US9707184B2 (en) 2014-07-17 2017-07-18 Pharmaceutical Manufacturing Research Services, Inc. Immediate release abuse deterrent liquid fill dosage form
US10959958B2 (en) 2014-10-20 2021-03-30 Pharmaceutical Manufacturing Research Services, Inc. Extended release abuse deterrent liquid fill dosage form

Also Published As

Publication number Publication date
EP1893183A4 (fr) 2010-08-18
CA2612044C (fr) 2016-02-02
JP2008543851A (ja) 2008-12-04
CA2612044A1 (fr) 2006-12-28
EP1893183A1 (fr) 2008-03-05

Similar Documents

Publication Publication Date Title
US9060950B2 (en) Emetic embedded capsule
US11872307B2 (en) Liquisoft capsules
AU2005305232B2 (en) Non-gelatin soft capsule system
US7524515B2 (en) Pharmaceutical safety dosage forms
EP1868585B1 (fr) Capsules a l'epreuve d'abus
CA2612044C (fr) Capsule contenant un emetique
Gauri et al. Fast dissolving drug delivery and its technologies.
HUT54038A (en) Process for producing compositions with hydrogel-operated controlled release of active ingredient
US10166207B2 (en) Acamprosate formulations, methods of using the same, and combinations comprising the same
WO1995002395A1 (fr) Formes posologiques encapsulees
US10357461B2 (en) Physically dispersed, molecularly dissolved and/or chemically bound drug(s) in an empty, hard capsule shell composition
AU2006275718A1 (en) Pharmaceutical formulations/composition of guanfacine suitable for single dose form adminstration daily
EP1177788B1 (fr) Composition pharmaceutique à base de fluoxétine sous forme de comprimés enrobés dispersibles et son procédé de fabrication
Ubhe et al. A brief overview on tablet and it’s types
JP2006515603A (ja) 粉末医薬組成物
EP2853262B1 (fr) Traitement de l'érythème solaire utilisant des analgésiques et des antihistaminiques
AU2003224419A1 (en) Orally administrable pharmaceutical formulation
US20180110750A1 (en) Hydroxycitric acid compounds and capsule liquid delivery
US20080274188A1 (en) Oral Vehicle For Systemic Pharmaceuticals
US20190343770A1 (en) Hard Capsule Shell Compositions for the Oral Contraceptive Formulations
AU687420B2 (en) Soft-shelled gelatin encapsulated particles
EP3716955B1 (fr) Capsule de gel liquide à double chambre souple et procédé d'administration de compositions de cannabis sublinguale et ingérable
US20030158263A1 (en) Orally administrable pharmaceutical formulation
US20180256671A1 (en) Hard Capsule Shell Compositions for the Treatment of Irritable Bowel Syndrome
US20110092532A1 (en) Apomorphine pharmaceutical dosage security system

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
ENP Entry into the national phase

Ref document number: 2612044

Country of ref document: CA

Ref document number: 2008517007

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

REEP Request for entry into the european phase

Ref document number: 2006773005

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2006773005

Country of ref document: EP