Multimodal Abuse Resistant and Extended Release Opioid Formulations

• US 20100249045A1
• Filed: 04/26/2008
• Published: 09/30/2010
• Est. Priority Date: 11/02/2005
• Status: Active Grant

• Current Assignee: Relmada Therapeutics, Inc.
• Original Assignee: TheraQuest Biosciences, Inc.
• Inventors: Babul, Najib
• Granted Patent: US 9,125,833 B2
• Time in Patent Office: Days
• US Class Current: 514/21.400
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 9/485 Inorganic compounds
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

The present invention is in the field of oral, abuse resistant pharmaceutical compositions of opioid agonists, extended release pharmaceutical compositions of opioid agonists and extended release abuse resistant pharmaceutical compositions of opioid agonists and the use thereof. The present invention is also directed to extended release pharmaceutical compositions and the use thereof for preventing or minimizing the risk of abuse and/or toxicity from either intentional or unintentional tampering. The present invention is further directed at a method of preventing or minimizing the risk of abuse and/or toxicity from either intentional or unintentional tampering.

Claims

1-94. -94. (canceled)

95. A dosage form for administration via the oral cavity, the dosage form comprising

a) a drug combined with

b) at least two ADER ingredients selected from the group consisting of

(i) hydrogenated vegetable oils;

(ii) polyoxyethylene stearates;

(iii) glycerol monostearate; and

(iv) poorly water soluble waxes having a melting point in the range from 45 to 100 degrees Celsius;

wherein the ADER ingredients are selected and are present in amounts sufficient to reduce the amount of drug released from the dosage form in the USP Basket and Paddle Method at 100 revolutions per minute in 700 milliliters of simulated gastric fluid at 37 degrees Celsius, relative to the same dosage form lacking the ADER ingredients.

96. The dosage form of claim 95, wherein the drug is in a form selected from the group consisting of a pharmaceutically acceptable salt of the drug, a prodrug, an ester of the drug, an analog of the drug, a derivative of the drug, a solvated form of the drug, a complex comprising the drug, a metabolite of the drug, and combinations of these.

97. The dosage form of claim 95, comprising a type I hydrogenated vegetable oil.

98. The dosage form of claim 95, comprising a polyoxyethylene monostearate.

99. The dosage form of claim 95, comprising a polyoxyethylene distearate.

100. The dosage form of claim 95, comprising at least three of (i)-(iv).

101. The dosage form of claim 95, comprising each of (i)-(iv).

102. The dosage form of claim 95, wherein the ADER ingredients are present in an amount effective to render the dosage form abuse resistant.

103. The dosage form of claim 95, wherein the ADER ingredients are present in an amount effective to render the dosage form extended release.

104. The dosage form of claim 95, wherein the ADER ingredients are present in an amount effective to render the dosage form both abuse resistant and extended release.

105. The dosage form of claim 95, wherein the ADER ingredients are present in an amount effective to render the dosage form resistant to dose dumping due upon co-ingestion intact with alcohol.

106. The dosage form of claim 95, wherein the ADER ingredients are present in an amount effective to render the dosage form resistant to significant changes in oral bioavailability attributable to changes in food intake.

107. The dosage form of claim 95, wherein the ADER ingredients are present in an amount effective to render the dosage form resistant to intentional or surreptitious adulteration of beverages.

108. The dosage form of claim 95, wherein the ADER ingredients are present in an amount effective to render the dosage form buoyant.

109. The dosage form of claim 95, wherein the ADER ingredients are present in an amount effective to reduce toxicity from intentional or inadvertent tampering of the dosage form.

110. The dosage form of claim 95, wherein the ADER ingredients are present in an amount effective to reduce the rate of release of the drug, relative to the dosage form lacking the ADER ingredients, when administered to a human.

111. The dosage form of claim 95, wherein the drug is an opioid agonist selected from the group consisting of alfentanil, allylprodine, alphaprodine, anileridine, apomorphine, apocodeine, ben-zylmorphine, bezitramide, brifentanil, buprenorphine, butorphanol, carfentanil, clonitazene, codeine, cyclorphen, cyprenorphine, desomorphine, dextromoramide, dezocine, diampromide, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxyaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene, fentanyl, heroin, hydrocodone, hydroxymethylmorphinan, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levallorphan, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, methylmorphine, metopon, mirfentanil, morphine, morphine-6-glucuronide, myrophine, nalbuphine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, nociceptin/orphanin FQ (N/OFQ), normorphine, norpipanone, ohmefentanyl, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, pholcodine, piminodine, piritramide, propheptazine, promedol, profadol, properidine, propiram, propoxyphene, remifentanil, sufentanil, tapentadol, tramadol, trefentanil, tilidine, nalbuphine, or any opioid having agonist activity at an opioid receptor belonging to the phenanthrene, morphinan, benzomorphan, methadone, phenylpiperidine, propionanilide 4-anilidopiperidine, 4-aryl piperidines, and 4-Heteroarylpiperidines class, any opioid having agonist activity at an opioid receptor having the same pentacyclic nucleus as nalmefene, naltrexone, buprenorphine, levorphanol, meptazinol, pentazocine and dezocine, any drug having agonist activity at an opioid receptor which is a fentanyl analog, and prodrugs, analogs, derivatives, pharmaceutically acceptable salts thereof and mixtures thereof in racemic or enantiomeric form.

112. The dosage form of claim 95, further comprising an aversive agent.

113. A method of treating a medical condition amenable to treatment with an opioid agonist, the method comprising administering to the oral cavity of a human patient afflicted with the condition an effective amount of a dosage form comprising

a) an opioid agonist combined with

b) at least two ADER ingredients selected from the group consisting of

(i) hydrogenated vegetable oils;

(ii) polyoxyethylene stearates;

(iii) glycerol monostearate; and

(iv) poorly water soluble waxes having a melting point in the range from 45 to 100 degrees Celsius;

wherein the ADER ingredients are selected and are present in amounts sufficient to reduce the amount of the agonist released from the dosage form in the USP Basket and Paddle Method at 100 revolutions per minute in 700 milliliters of simulated gastric fluid at 37 degrees Celsius, relative to the same dosage form lacking the ADER ingredients.

114. A method of reducing the rate of release of an opioid agonist from an orally-administrable dosage form, the method comprising combining the agonist with at least two ADER ingredients selected from the group consisting of

(i) hydrogenated vegetable oils;

(ii) polyoxyethylene stearates;

(iii) glycerol monostearate; and

(iv) poorly water soluble waxes having a melting point in the range from 45 to 100 degrees Celsius.