Sublingual opioid formulations containing naloxone
Sublingual formulations containing an opioid, preferably, fentanyl or a pharmaceutically acceptable salt or ester thereof, naloxone or a pharmaceutically acceptable salt or ester thereof, and a terpene; as well as methods of treating pain by administering the formulations of the invention to a patient in need thereof.
1. A sublingual hydroalcoholic formulation comprising:
an opioid selected from the group consisting of alfentanil, butorphanol, codeine, diamorphine, dextromoramide, dezocine, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, meptazinol, methadone, morphine, nalbuphine, nalorphine, opium, oxycodone, oxymorphone, pentazocine, propoxyphene, remifentanyl, sufentanyl, tapentadol, and tramadol, and pharmaceutically acceptable salts thereof;
an alcohol;
propylene glycol; and
naloxone or a pharmaceutically acceptable salt or ester thereof, and/or a terpene, wherein the formulation is suitable for sublingual administration.
2. The formulation of claim 1 , wherein the opioid is fentanyl.
3. The formulation of claim 1 , wherein the terpene is selected from the group consisting of menthol, limonene, linalool, cineole, nerolidol, farnesol, geraniol, carvone, terpinolene, and ascaridole.
4. The formulation of claim 1 wherein the terpene is menthol.
5. The formulation of claim 1 , wherein the alcohol is ethanol.
6. The formulation of claim 1 , wherein the opioid is present at a concentration from 0.1% to 2% weight by weight of the total formulation.
7. The formulation of claim 1 , wherein naloxone or the pharmaceutically acceptable salt or ester thereof is present at a concentration from 0.01% to 20% weight by weight of the total formulation.
8. The formulation of claim 7 , wherein naloxone or the pharmaceutically acceptable salt or ester thereof is present at a concentration from 0.1% to 1.6% weight by weight of the total formulation.
9. The formulation of claim 1 wherein propylene glycol is present at a concentration from 1% to 10% weight by weight of the total formulation.
10. The formulation of claim 9 , wherein propylene glycol is present at a concentration from 4% to 6% weight by weight of the total formulation.
11. The formulation of claim 5 , wherein ethanol is present at a concentration from 20% to 80% weight by weight of the total formulation.
12. The formulation of claim 11 , wherein ethanol is present at a concentration from 40% to 60% weight by weight of the total formulation.
13. The formulation of claim 4 , wherein the concentration of menthol is from 0.1% to 10% weight by weight of the total formulation.
14. The formulation of claim 13 , wherein the concentration of menthol is 0.05% to 0.5% weight by weight of the total formulation.
15. The formulation of claim 1 further comprising xylitol.
16. A method of treating pain comprising administering to a patient in need thereof a therapeutically effective amount of a formulation of claim 1 .