Methods and compositions for deterring abuse of opioid containing dosage forms
View Patent ↗This invention relates to an abuse deterrent dosage form of opioid analgesics, wherein an analgesically effective amount of opioid analgesic is combined with a polymer to form a matrix.
1. A therapeutic pharmaceutical composition comprising a mixture including:
(a) at least one opioid analgesic agonistic to the mu-receptor selected from the group consisting of: alfentanil, buprenorphine, carfentanil, codeine, dezocine, diacetylmorphine, dihydrocodeine, dihydromorphine, fentanyl, hydrocodone, hydromorphone, β-hydroxy-3-methylfentanyl, levo-α-acetylmethadol, lofentanil, methadone, morphine, oxycodone, oxymorphone, propoxyphene, remifentanil, sufentanil, tilidine, and tramadol;
(b) at least one opioid analgesic agonistic to the kappa-receptor selected from the group consisting of: butorphanol, diprenorphine, etorphine, levorphanol, meperidine, nalbuphine, pentazocine, and pethidine;
(c) gel-forming polyethylene oxide at about 3 to about 40 percent by weight;
(d) at least one disintegrant at about 2 to 25 percent by weight wherein the disintegrant is selected from the group consisting of crospovidone, sodium starch glycolate, and croscarmellose sodium; and
(e) sodium lauryl sulfate at about 1 to 10 percent by weight.
2. The therapeutic pharmaceutical composition of claim 1 , wherein the polyethylene oxide has an average molecular weight ranging from 300,000 to about 5,000,000.
3. The therapeutic pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is in unit dose form.
4. The therapeutic pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is in suppository, capsule, caplet, pill, gel, soft gelatin capsule, or compressed tablet form.
5. The therapeutic pharmaceutical composition of claim 1 , wherein the analgesic is present in an amount of 0.5 to about 25 percent by weight.
6. The therapeutic pharmaceutical composition of claim 1 , wherein the opioid analgesic agonistic to the mu-receptor is hydrocodone or a pharmaceutically acceptable salt thereof; and the opioid analgesic agonistic to the kappa-receptor is selected from the group consisting of: butorphanol, diprenorphine, etorphine, levorphanol, meperidine, nalbuphine, pentazocine, and pethidine or a pharmaceutically acceptable salt thereof.
7. The therapeutic pharmaceutical composition of claim 1 , wherein the opioid analgesic agonistic to the mu-receptor is oxycodone or a pharmaceutically acceptable salt thereof; and the opioid analgesic agonistic to the kappa-receptor is selected from the group consisting of: butorphanol, diprenorphine, etorphine, levorphanol, meperidine, nalbuphine, pentazocine, and pethidine or a pharmaceutically acceptable salt thereof.
8. The therapeutic pharmaceutical composition of claim 1 , wherein the opioid analgesic agonistic to the mu-receptor is morphine or a pharmaceutically acceptable salt thereof; and the opioid analgesic agonistic to the kappa-receptor is selected from the group consisting of: butorphanol, diprenorphine, etorphine, levorphanol, meperidine, nalbuphine, pentazocine, and pethidine or a pharmaceutically acceptable salt thereof.
9. The therapeutic pharmaceutical composition of claim 1 , wherein the opioid analgesic agonistic to the mu-receptor is codeine or a pharmaceutically acceptable salt thereof; and the opioid analgesic agonistic to the kappa-receptor is selected from the group consisting of: butorphanol, diprenorphine, etorphine, levorphanol, meperidine, nalbuphine, pentazocine, and pethidine or a pharmaceutically acceptable salt thereof.
10. The therapeutic pharmaceutical composition of claim 1 , wherein the opioid analgesic agonistic to the mu-receptor is hydromorphone or a pharmaceutically acceptable salt thereof; and the opioid analgesic agonistic to the kappa-receptor is selected from the group consisting of: butorphanol, diprenorphine, etorphine, levorphanol, meperidine, nalbuphine, pentazocine, and pethidine or a pharmaceutically acceptable salt thereof.
11. The therapeutic pharmaceutical composition of claim 1 , wherein the opioid analgesic agonistic to the mu-receptor is propoxyphene or a pharmaceutically acceptable salt thereof; and the opioid analgesic agonistic to the kappa-receptor is selected from the group consisting of: butorphanol, diprenorphine, etorphine, levorphanol, meperidine, nalbuphine, pentazocine, and pethidine or a pharmaceutically acceptable salt thereof.
12. The therapeutic pharmaceutical composition of claim 1 , wherein the opioid analgesic agonistic to the mu-receptor is tramadol or a pharmaceutically acceptable salt thereof; and the opioid analgesic agonistic to the kappa-receptor is selected from the group consisting of: butorphanol, diprenorphine, etorphine, levorphanol, meperidine, nalbuphine, pentazocine, and pethidine or a pharmaceutically acceptable salt thereof.
13. The therapeutic pharmaceutical composition of claim 1 , wherein the opioid analgesic agonistic to the mu-receptor is selected from the group consisting of:
alfentanil, buprenorphine, carfentanil, codeine, dezocine, diacetylmorphine, dihydrocodeine, dihydromorphine, fentanyl, hydrocodone, hydromorphone, β-hydroxy-3-methylfentanyl, levo-α-acetylmethadol, lofentanil, methadone, morphine, oxycodone, oxymorphone, propoxyphene, remifentanil, sufentanil, tilidine, and tramadol or a pharmaceutically acceptable salt thereof; and the opioid analgesic agonistic to the kappa-receptor is meperidine or a pharmaceutically acceptable salt thereof.
14. The therapeutic pharmaceutical composition of claim 1 , wherein the opioid analgesic agonistic to the mu-receptor is methadone or a pharmaceutically acceptable salt thereof; and the opioid analgesic agonistic to the kappa-receptor is selected from the group consisting of: butorphanol, diprenorphine, etorphine, levorphanol, meperidine, nalbuphine, pentazocine, and pethidine or a pharmaceutically acceptable salt thereof.
15. The therapeutic pharmaceutical composition of claim 1 , wherein the opioid analgesic agonistic to the mu-receptor is selected from the group consisting of: alfentanil, buprenorphine, carfentanil, codeine, dezocine, diacetylmorphine, dihydrocodeine, dihydromorphine, fentanyl, hydrocodone, hydromorphone, β-hydroxy-3-methylfentanyl, levo-α-acetylmethadol, lofentanil, methadone, morphine, oxycodone, oxymorphone, propoxyphene, remifentanil, sufentanil, tilidine, and tramadol or a pharmaceutically acceptable salt thereof; and the opioid analgesic agonistic to the kappa-receptor is pentazocine or a pharmaceutically acceptable salt thereof.
16. The therapeutic pharmaceutical composition of claim 1 , wherein the disintegrant comprises crosprovidone.
17. The therapeutic pharmaceutical composition of claim 7 , wherein the disintegrant comprises crosprovidone.
18. A therapeutic pharmaceutical composition comprising a mixture including:
(a) an opioid analgesic agonistic to the mu-receptor;
(b) an opioid analgesic agonistic to the kappa-receptor;
(c) gel-forming polyethylene oxide at about 3 to about 40 percent by weight;
(d) at least one disintegrant at about 2 to 25 percent by weight wherein the disintegrant is selected from the group consisting of crospovidone, sodium starch glycolate, and croscarmellose sodium; and
(e) sodium lauryl sulfate at about 1 to 10 percent by weight.