Multimodal abuse resistant and extended release opioid formulations
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.
1. A dosage form for administration via the oral cavity, the dosage form comprising
a) a drug, being an opioid agonist, combined with
b) at least two abuse deterrent extended release (ADER) ingredients including a hydrogenated vegetable oil and a fractionated coconut oil,
wherein the ADER ingredients are selected and are present in amounts sufficient to reduce the amount of drug released from the dosage form at one hour 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, and
wherein the fractionated coconut oil is present in an amount sufficient to enhance by at least a third resistance to powdering of the dosage form to particle sizes of 650 micrometers or less, relative to an otherwise identical dosage form having the hydrogenated vegetable oil substituted in place of the fractionated coconut oil.
2. The dosage form of claim 1 , wherein the drug is in a form selected from the group consisting of a pharmaceutically acceptable salt of the drug, an ester of the drug, and combinations of these.
3. The dosage form of claim 1 , wherein the hydrogenated vegetable oil is hydrogenated cottonseed oil.
4. The dosage form of claim 1 , 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.
5. The dosage form of claim 1 , wherein the drug is an opioid agonist selected from the group consisting of alfentanil, allylprodine, alphaprodine, anileridine, apomorphine, apocodeine, benzylmorphine, 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, pharmaceutically acceptable salts thereof and mixtures thereof.
6. The dosage form of claim 1 , further comprising an aversive agent.
7. 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 the dosage form of claim 1 .
8. The dosage form of claim 1 , further comprising a third ADER ingredient selected from the group consisting of hydroxypropyl methyl celluloses and thixotropes.
9. The dosage form of claim 8 , comprising both a hydroxypropyl methyl cellulose and a thixotrope.
10. The dosage form of claim 9 , wherein the thixotrope is a fumed silicon dioxide.
11. The dosage form of claim 1 , wherein the opioid agonist is levorphanol.
12. The dosage form of claim 11 , wherein the levorphanol is present in the form of levorphanol tartrate.
13. The dosage form of claim 12 , comprising four ADER ingredients, being hydrogenated cottonseed oil, fractionated coconut oil, hydroxypropyl methyl cellulose, and fumed silicon dioxide.
14. The dosage form of claim 1 , wherein the drug is an opioid agonist selected from the group consisting of opioids having agonist activity at an opioid receptor belonging to the phenanthrene, morphinan, benzomorphan, methadone, phenylpiperidine, propionanilide 4-anilidopiperidine, 4-aryl piperidines, and 4-Heteroarylpiperidines classes.
15. The dosage form of claim 1 , wherein the drug is an opioid agonist selected from the group consisting of opioids having agonist activity at an opioid receptor having the same pentacyclic nucleus as any of nalmefene, naltrexone, buprenorphine, levorphanol, meptazinol, pentazocine and dezocine.
16. The dosage form of claim 1 , wherein the dosage form comprises the fractionated coconut oil in an amount from 15 to 30% w/w.
17. The dosage form of claim 1 , wherein the dosage form is a capsule and comprises the fractionated coconut oil in an amount from 15 to 30% w/w of the capsule contents.
18. The dosage form of claim 1 , wherein the weight ratio of hydrogenated vegetable oil:fractionated coconut oil is from 7:5 to 3.
19. The dosage form of claim 1 , wherein the opioid agonist is butorphanol.
20. The dosage form of claim 1 , wherein the opioid agonist is buprenorphine.