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(12) Patent Application Publication (10) Pub. No.: US 2005/0112067 A1 Kumar Et Al

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(12) Patent Application Publication (10) Pub. No.: US 2005/0112067 A1 Kumar Et Al US 2005O112067A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0112067 A1 Kumar et al. (43) Pub. Date: May 26, 2005 (54) METHODS AND COMPOSITIONS FOR (22) Filed: Nov. 26, 2003 DETERRING ABUSE OF OPOD CONTAINING DOSAGE FORMS Publication Classification (76) Inventors: Vijai Kumar, Morris Plains, NJ (US); (51) Int. Cl.' ........................ A61 K 49/00; A61K 31/485 David Dixon, Woodside, NY (US); (52) U.S. Cl. ........................................... 424/10.1; 514/282 Divya Tewari, Suffern, NY (US); Dilip B. Wadgaonkar, Suffern, NY (US) (57) ABSTRACT Correspondence Address: MORGAN, LEWIS & BOCKIUS LLP 1701 MARKET STREET This invention relates to an abuse deterrent dosage form of PHILADELPHIA, PA 19103-2921 (US) opioid analgesics, wherein an analgesically effective amount of opioid analgesic is combined with a polymer to form a (21) Appl. No.: 10/723,654 matrix. Patent Application Publication May 26, 2005 Sheet 1 of 9 US 2005/0112067 A1 Extractin f Opioids from immediatel controlled release formulations O O 103 99 E st 9 s ?o t e . o S3 vid x C b O SS Oxycodone Hydrocodone Oxyconting)" Hydrochloride Bitaritrate (Controlled release) (Immediate release) (immediate release) Fig. 1 Patent Application Publication May 26, 2005 Sheet 2 of 9 US 2005/0112067 A1 Extraction f opioids from anti-abuse formulation 100 8 O 6 O 4O 2 O O Oxycodone Hydrocodone Morphine Hydrochloride Bitatrate Sulfate (immediate release) (Immediate release) (Immediate release) Fig. 2 * Extraction process of opioids for anti-abuse properties is the same for figure l and figure 2. ** Marketed Oxycodone formulation from Purdue Pharma. Patent Application Publication May 26, 2005 Sheet 3 of 9 US 2005/0112067 A1 4. as S. bp E E 3: SD en E on 5 s < C. L. l 5 2 C. -t SC QN)r D. C. A .S. C s O O O O OO N CO LO w CD CN v s peoeux finiO 9/ Patent Application Publication May 26, 2005 Sheet 4 of 9 US 2005/0112067 A1 SnO?IBAJOSÐI?0JAUIO!]n[OSSICI «20?06080/090907090Z010 (sº)nu?uu)au?L 06 08 0/ 09 09 07 0€ OZ 0|| pe NIOSSIO find % Patent Application Publication May 26, 2005 Sheet 5 of 9 US 2005/0112067 A1 Figure 5a Patent Application Publication May 26, 2005 Sheet 6 of 9 US 2005/0112067 A1 Figure 5b Patent Application Publication May 26, 2005 Sheet 7 of 9 US 2005/0112067 A1 Figure 5c Patent Application Publication May 26, 2005 Sheet 8 of 9 US 2005/0112067 A1 Figure 6: Process Flow Chart Patent Application Publication May 26, 2005 Sheet 9 of 9 US 2005/0112067 A1 siº?qeiJL£IOHJoSºI?ouduonnossig US 2005/01 12067 A1 May 26, 2005 METHODS AND COMPOSITIONS FOR parenteral (e.g. intravenous injection), 2) intranasal (e.g., DETERRING ABUSE OF OPOD CONTAINING Snorting), and 3) repeated oral ingestion of excessive quan DOSAGE FORMS tities of orally administered tablets or capsules. One mode of abuse of oral Solid drugs involves the extraction of the FIELD OF INVENTION opioid component from the dosage form by first mixing the dosage form with a Suitable Solvent (e.g., water), and then 0001. This invention pertains to abuse deterrent compo Subsequently extracting the opioid component from the Sitions containing a drug (e.g., an analgesic opioid). Addi mixture for use in a Solution Suitable for intravenous injec tionally, the invention relates to a method of administering tion of the opioid to achieve a “high.” a dose of an analgesic from a dosage form, which is abuse deterrent. 0007 Attempts have been made to diminish abuse of orally administered opioid drugs. These attempts generally centered on the inclusion in the oral dosage form of an BACKGROUND OF THE INVENTION opioid antagonist which is not orally active but which will 0002 The class of drugs exhibiting opium or morphine Substantially block the analgesic effects of the opioid if one like properties are referred to as opioids, or opioid agonists. attempts to dissolve the opioid and administer it parenterally. Certain opioids act as agonists, interacting with Stereo 0008 For example, commercially available Talwing)NX Specific and Saturable binding sites in the brain and other tablets from Sanofi-Winthrop contain a combination of tissues. Endogenous opioid-like peptides are present in areas pentazocine and naloxone. Pentazocine is a partial agonist of of the central nervous System that are presumed to be related tl receptors and also has affinity for K receptors, whereas, to the perception of pain; to movement, mood and behavior, naloxone is an antagonist of u receptors. Talwin RNX con and to the regulation of neuroendocrinological functions. tains pentazocine hydrochloride equivalent to 50 mg base Three classical opioid receptor types, mu (), delta (Ö), and and naloxone hydrochloride equivalent to 0.5 mg base. kappa (K), have been Studied extensively. Each of these Talwin ENX is indicated for the relief of moderate to severe receptorS has a unique anatomical distribution in the brain, pain. The amount of naloxone present in this combination Spinal cord, and the periphery. Most of the clinically used has no action when taken orally, and will not interfere with opioids are relatively Selective for u receptors, reflecting the pharmacologic action of pentazocine. However, this their similarity to morphine. However, it is important to note amount of naloxone given by injection has profound antago that opioid containing drugs that are relatively Selective at nistic action to opioid analgesics. Thus, the inclusion of standard doses will often interact with additional receptor naloxone is intended to curb a form of misuse of oral Subtypes when given at Sufficiently high doses, leading to pentazocine, which occurs when the dosage form is Solubi possible changes in their pharmacological effect. This is lized and injected. Therefore, this dosage has lower potential especially true as opioid doses are escalated to overcome for parenteral misuse than previous oral pentazocine formu tolerance. lations. 0003. The potential for the development of tolerance, 0009 U.S. Pat. No. 6.559,159 (Carroll et al.) describes physical and/or psychological, dependence (i.e., addiction) the use of kappa receptors antagonist for the treatment of with repeated opioid use is a characteristic feature of most opioid related addictions. One Such compound is naltrexone, opioid containing drugs. The possibility of developing which is commercially available in the tablet form Revia(E) addiction is one of the major concerns in the use of opioids for the treatment of alcohol dependence and for the blockade for the management of pain. Another major concern asso of exogenously administered opioids. (Physicians Desk Ref ciated with the use of opioids is the diversion of these drugs from a patient in legitimate pain to other individuals (non erence 57" ed., Montvale, N.J.) patients) for recreational purposes. 0010 U.S. Pat. No. 6,375,957 (Kaiko et al.) describes in detail the combination of opioid agonist, NSAID, and an 0004 Drug abusers and/or addicts typically may take a orally active opioid antagonist. The purpose of adding the dosage form containing one or more opioid analgesics and opioid antagonist is the same as discussed above. crush, shear, grind, chew, dissolve and/or heat, extract or otherwise damage the product So that a significant amount or 0.011 U.S. Pat. No. 4,457.933 (Gordon et al.) describes in even an entire amount of the drug becomes available for detail a method for decreasing both the oral and parenteral immediate absorption by 1) injection, 2) inhalation, and/or abuse potential of analgesic agents Such as Oxycodone, 3) oral consumption. propoxyphene and pentazocine by combining an analgesic dose of the analgesic agents with naloxone in Specific, 0005 There are three basic patterns of behavior leading relatively narrow ranges. to opioid abuse. The first involves individuals whose opioid drug use begins in the context of medical treatment and who 0012 U.S. Pat. No. 6.228,863 B1 (Palermo et al.) obtain their initial drug Supplies through prescriptions from describes a method for reducing the abuse potential of an physicians. The Second begins with experimental or “recre oral dosage form of an opioid analgesic, whereby an orally ational’ drug use and progresses to more intensive use. A active opioid agonist is combined with an opioid antagonist third pattern of abuse involves users who begin in one or into an oral dosage form requiring at least a two-step another of the preceding ways but later Switch to oral opioids extraction process to be separated from the opioid agonist, Such as methadone, obtained from organized addiction treat the amount of opioid antagonist included being Sufficient to ment programs. counteract opioid effects if extracted together with the opioid agonist and administered parenterally. 0006 There are various routes of administration an abuser may commonly attempt to abuse an opioid containing 0013 The prior art describes several other methods and drug formulation. The most common methods include 1) compositions to minimize the abuse of an opioid containing US 2005/01 12067 A1 May 26, 2005 drug. One such method is discussed in U.S. Pat. No. Such that emesis ensues only if more than a prescribed 6,593,367 (Dewey et al.), describing a method whereby the amount of the analgesic is consumed, and combining the addiction-related behavior of a mammal Suffering from analgesic, gel forming polymer, nasal tissue irritant and addiction could be changed by a combination of drugs. The emetic to form a therapeutic composition. method includes administering to the mammal an effective 0019. The present invention includes a therapeutic phar amount of gamma vinyl GABA (GVG) or a pharmaceuti maceutical composition including an analgesic, a gel form cally acceptable Salt, or an enantiomer or a racemic mixture, ing polymer, a Surfactant present in Sufficient amount to where the effective amount is Sufficient to diminish, inhibit cause mucosal tissue irritation, and an emetic in Sufficient or eliminate behavior associated with craving or use of the amount to cause emesis if greater than a prescribed amount combination of abused drugs.
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