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(12) Patent Application Publication (10) Pub. No.: US 2014/0275038A1 Shah Et Al

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(12) Patent Application Publication (10) Pub. No.: US 2014/0275038A1 Shah Et Al US 20140275038A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0275038A1 Shah et al. (43) Pub. Date: Sep. 18, 2014 (54) ABUSE DETERRENT COMPOSITIONS AND Publication Classification METHODS OF USE (51) Int. Cl. (71) Applicant: uprig. Detry Ishologies, LLC, A613 L/485 (2006.01) y 2C, A6II 45/06 (2006.01) (72) Inventors: Manish S. Shah, West Caldwell, NJ (52) U.S. Cl. (US); Ray J. DiFalco, Ridgewood, NJ CPC ............... A61K 31/485 (2013.01); A61K 45/06 (US); Stefan Aigner, Valley Cottage, NY (2013.01) (US) USPC ...................................... 514/217.11: 514/282 (73) Assignee: Inspirion Delivery Technologies, LLC, Valley Cottage, NY (US) 57 ABSTRACT (21) Appl. No.: 14/218,791 (57) (22) Filed: Mar 18, 2014 O O Orallyy administrable ppharmaceutical compositions,p methods Related U.S. Application Data of administration, and methods of making the same are pro (60) Provisional application No. 61/799,096, filed on Mar. vided. The pharmaceutical compositions provide abuse deter 15, 2013. rent properties. Patent Application Publication Sep. 18, 2014 US 2014/0275038A1 Morphine ARER 100 mg Extraction in Ethanol (N =5) 100 90 Zintact 30 Minutes 80 EX Intact 240 Minutes O E Ground 30 Minutes O NGround 240 Minutes O O O 20 10 R O ZZZZZZZ Water 5%. Ethanol 10%. Ethanol 20% Ethanol 40%. Ethanol F.G. 1 US 2014/0275038A1 Sep. 18, 2014 ABUSE DETERRENT COMPOSITIONS AND 0007. Oxymorphone, also known as 14-hydroxydihydro METHODS OF USE morphinone and 4.5C.-epoxy-3, 14-dihydroxy-17-methyl morphinan-6-one, is an opioid analgesic used for the treat CROSS REFERENCE TO RELATED ment of pain. Major metabolites of oxymorphone include APPLICATION oxymorphone-3-glucuronide and 6-hydroxy-oxymorphone. 0008 Hydrocodone, which is also known as 4.5C.-epoxy 0001. This application claims the benefit of U.S. Patent 3-methoxy-17-methylmorphinan-6-one, is an opioid analge Provisional Application No. 61/799,096, filed on Mar. 15, sic used for the treatment of pain. Major metabolites of hydro 2013, which is incorporated herein by reference. codone include norhydrocodone and hydromorphone. 0009 Hydromorphone, which is also known as 4.5-C.- FIELD OF THE INVENTION epoxy-3-hydroxy-17-methyl morphinan-6-one, is an opioid 0002 The present invention provides orally administrable analgesic. Major metabolites of hydromorphone include pharmaceutical compositions, methods of administration, hydromorphone-3-glucuronide, hydromorphone-3-gluco and methods of making the same. side and dihydroisomorphine-6-glucuronide. 0010 Codeine, which is also known as a (5C,6C.)-7,8- BACKGROUND OF THE INVENTION didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6- ol, is an opioid used for its analgesic, antitussive, antidiar 0003. The present invention relates to orally administrable rheal, antihypertensive, anxiolytic, antidepressant, sedative pharmaceutical compositions, and specifically relates to and hypnotic properties. Major metabolites of codeine compositions that are designed to reduce the potential for include codeine-6-glucuronide (C6G), norcodeine, hydroc improper administration of medications and their use in a odone, morphine, morphine-3-glucuronide, morphine-6-glu non-indicated or non-prescribed manner. The present inven curonide, and normorphine. tion can comprise any drug, and it is especially useful with 0011 Central nervous stimulants are often used to medications that are Subject to abuse. Such as drugs affecting increase mental alertness, and they can results in feelings of the central nervous system. For example, the present inven exhilaration and energy. Examples of Such drugs include tion is particularly useful for pain medications, medications amphetamines such as methylphenidate, dextroamphet to reduce or eliminate anxiety attacks, stimulants and sleep ing pills. With these general types of drugs, there is the poten amine, and lisdexamfetamine. 0012 Methylphenidate, which is also known as methyl tial of abuse and improper administration that may result in phenyl(piperidin-2-yl)acetate, is a drug often used for treat drug overdose, addiction, Suboptimal efficacy, and/or death. ment of narcolepsy, attention-deficit/hyperactivity disorder, 0004 Opioid agonists are substances that act by attaching and depression. Major metabolites of methylphenidate to specific proteins called opioid receptors, which are found include but are not limited to ethylphenidate, ritalinic acid in the brain, spinal cord, and gastrointestinal tract. When (CL-phenyl-2-piperidine acetic acid), hydroxymethylpheni these drugs attach to certain opioid receptors in the brain and spinal cord, they can effectively block the transmission of date, and hydroxyritalinic acid. pain messages to the brain. Opioid analgesics Such as oxyc 0013 Dextroamphetamine, which is also known as (2S)- odone, morphine, oxymorphone, hydrocodone and hydro 1-phenylpropan-2-amine, is a drug used for treatment of nar morphone are Successful and therapeutically useful pain colepsy, attention-deficit/hyperactivity disorder, and depres medications. Opioids undergo phase 1 metabolism by the sion. Major metabolites of dextroamphetamine include but cytochrome P450(CYP) pathway, phase 2 metabolism by are not limited to 4-hydroxyamphetamine, benzoic acid, phe conjugation, or both, as described in Smith H. "Opioid nylacetone, hippuric acid, 4-hydroxynorephedrine, and Metabolism.” Mayo Clin. Proc., 2009; 84(7):613-624. norephedrine. 0005 Morphine, also known as (5C,6O)-7,8-didehydro-4, 0014 Lisdexamfetamine, also known as lisdexamfe 5-epoxy-17-methylmorphinan-3,6-diol, is an example of a tamine, is another stimulant. It is a prodrug of phenethy potent opioid analgesic used in the treatment of acute, lamine and amphetamines such as dextroamphetamine. chronic, and severe pain. Major metabolites of morphine 00.15 Benzodiazepines are commonly used to treat anxi include morphine-3-glucuronide (M3G), morphine-6-glucu ety. Examples of benzodiazepines include, but are not limited ronide (M6G), hydromorphone, normorphine (NM) and to alprazolam, lorazepam, and diazepam. minor metabolites Such as morphine-3,6-diglucuronide, mor 0016 Alprazolam, which is also known as 8-chloro-1- phine-3-ethereal Sulfate, normorphine-6-glucuronide, and methyl-6-phenyl-4H-1,2,4-triazolo 4.3-a 1,4)benzodiaz normorphine-3-glucuronide. Morphine-6-glucuronide epine, is a short acting anxiolytic. Major metabolites of alpra (M6G), a major metabolite of morphine, is formed by glucu Zolam include, but are not limited to 4-hydroxyalprazolam ronidation. M6G and morphine both demonstrate analgesic and O-hydroxyalprazolam. activity. 0017 Lorazepam, which is also known as (RS)-7-Chloro 0006. Oxycodone, also known as (5R,9R,13S, 14S)-4,5C.- 5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-2H-1,4-benzo epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one, diazepin-2-one, is an anxiolytic agent having intermediate is an opioid analgesic used for the treatment of pain. Major duration of action. Major metabolites of lorazepam include, metabolites of oxycodone include norOxycodone, C. oxy but are not limited to, 3-O-phenolic glucuronide and codol, B oxycodol, oxymorphone, C. Oxymorphol. 3 oxymor lorazepam glucuronide. phol, noroxymorphone, C. noroxycodol, B noroxycodol. 0018 Diazepam, which is also known as 7-chloro-1,3- noroxymorphone, 14-hydroxydihydrocodeine, and 14-hy dihydro-1-methyl-5-phenyl-1,4-benzodiazepin-2(3H)-one, droxydihydromorphine. Oxymorphone and noroxycodone is a commonly used anxiolytic. Major metabolites of diaz are the most commonly known major metabolites of oxyc epam include, but are not limited to desmethyldiazepam, odone. eSmethyldiazepam, oxazepam, and temazepam. US 2014/0275038A1 Sep. 18, 2014 0019 While pain medications, medications to reduce or composition is released after 60 minutes under the following eliminate anxiety attacks (psychotherapeutic drugs), stimu dissolution conditions: DI water, 500 mL, USP Apparatus 2 lants and sleeping pills can be safe, effective, and therapeu (Paddle), 50 rpm, 37° C. tically useful when administered properly, such drugs are 0024. The present invention also provides an orally Susceptible to abuse. Examples of Such compositions include administrable pharmaceutical composition comprising a but are not limited to ROXICODONER) (oxycodone tablets), drug, wherein the composition is configured Such that when OXYCONTINR) (oxycodone tablets), DILAUDIDR (hydro the pharmaceutical composition is administered intranasally morphone tablets), OPANAR and OPANA ER(R) (oxymor in physically compromised form to a subject, the area under phone tablets), MS CONTINR) (morphine tablets), CON the curve (AUC) of drug after a period of time is less than CERTAR, METHYLINR, RITALINR, RITALIN LAR), and 200% of the AUC of the drug achieved after oral administra EQUASYM KL(R) (methylphenidate tablets and capsules), tion of an intact form of the pharmaceutical composition after FOCALINR) (dexmethylphenidate capsules), ADDER the same period of time. ALL(R), DEXEDRINE(R), and DEXTROSTATR) (dextroam 0025. The present invention provides an orally adminis phetamine tablets and capsules), VYVANSER (lisdexamfe trable pharmaceutical composition comprising a drug, tamine capsules), ATIVANR) (lorazepam), XANAX(R) wherein the composition is configured such that when the (alprazolam), and VALIUM(R) (diazepam). pharmaceutical composition is administered intranasally in 0020. A sense of euphoria or “high can be experienced physically compromised form to a Subject, the area under the with high serum concentrations of these drugs. Individuals
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