Pharmaceutical compositions
Methods and compositions are provided which comprise effective amounts of analgesic to treat a subject, including reducing or eliminating an adverse effect associated with the analgesic.
1. A method for treating pain, and reducing or preventing opioid-induced nausea or vomiting, the method comprising administering a solid oral pharmaceutical composition to a subject in need thereof, wherein the solid oral pharmaceutical composition comprises:
an immediate-release matrix comprising an antiemetic; and
a controlled-release matrix comprising an opioid analgesic and a non-opioid analgesic, wherein the solid oral pharmaceutical composition demonstrates the following dissolution profile: wherein about 90% of the antiemetic is released in about 1 minute to about 20 minutes following contact of the solid oral pharmaceutical composition with a dissolution fluid as measured by a USP Apparatus 2 (Paddle Apparatus), wherein about 30% to about 60% of the opioid analgesic is released in about 5 to 10 minutes following contact of the solid oral pharmaceutical composition with a dissolution fluid as measured by a USP Apparatus 2 (Paddle Apparatus), and wherein about 100% of the opioid analgesic is released in about 60 minutes following contact of the solid oral pharmaceutical composition with a dissolution fluid as measured by a USP Apparatus 2 (Paddle Apparatus), and
wherein the solid oral pharmaceutical composition provides an effective amount of the opioid analgesic and the non-opioid analgesic to treat pain, and wherein the solid oral pharmaceutical composition provides an effective amount of the antiemetic to reduce or prevent nausea associated with the opioid analgesic or vomiting associated with the opioid analgesic.
2. The method of claim 1 , wherein the opioid analgesic is hydrocodone, oxycodone, acetyldihydrocodeinone, diamorphine, codeine, pethidine, alfentanil, buprenorphine, butorphanol, codeine, dezocine, fentanyl, hydromorphone, levomethadyl acetate, levorphanol, meperidine, methadone, morphine sulfate, nalbuphine, oxymorphone, pentazocine, propoxyphene, remifentanil, sufentanil, tramadol, or a pharmaceutically acceptable salt thereof.
3. The method of claim 1 , wherein the opioid analgesic is present in an amount of about 5 mg, about 7.5 mg, about 10 mg, about 15 mg, about 20 mg, or about 30 mg.
4. The method of claim 2 , wherein the opioid analgesic is hydrocodone bitartrate.
5. The method of claim 1 , wherein the opioid analgesic is hydrocodone or a pharmaceutically acceptable salt thereof, and is present in an amount of about 7.5 mg.
6. The method of claim 5 , wherein the pharmaceutically acceptable salt of the hydrocodone is hydrocodone bitartrate, and is present in an amount of about 7.5 mg.
7. The method of claim 1 , wherein the opioid analgesic is hydrocodone or a pharmaceutically acceptable salt thereof, and is present in an amount of about 5 mg or about 10 mg.
8. The method of claim 3 , wherein the opioid analgesic is hydrocodone or a pharmaceutically acceptable salt thereof, or oxycodone or a pharmaceutically acceptable salt thereof.
9. The method of claim 8 , wherein the opioid analgesic is oxycodone or the pharmaceutically acceptable salt thereof, and is present in an amount of about 7.5 mg.
10. The method of claim 8 , wherein the opioid analgesic is oxycodone or the pharmaceutically acceptable salt thereof, and is present in an amount of about 5 mg.
11. The method of claim 2 , wherein the opioid analgesic is a pharmaceutically acceptable salt of oxycodone that is oxycodone hydrochloride.
12. The method of claim 1 , wherein the antiemetic is promethazine or a pharmaceutically acceptable salt thereof.
13. The method of claim 12 , wherein the promethazine or the pharmaceutically acceptable salt thereof is present in an amount of about 11-14 mg.
14. The method of claim 13 , wherein the promethazine or the pharmaceutically acceptable salt thereof is present in an amount of about 12.5 mg.
15. The method of claim 14 , wherein the pharmaceutically acceptable salt of the promethazine is promethazine hydrochloride, and is present in an amount of about 12.5 mg.
16. The method of claim 13 , wherein the promethazine or the pharmaceutically acceptable salt thereof is present in an amount of about 11 mg.
17. The method of claim 12 , wherein the antiemetic is the pharmaceutically acceptable salt of the promethazine that is promethazine hydrochloride.
18. The method of claim 1 , wherein the non-opioid analgesic is acetaminophen or a pharmaceutically acceptable salt thereof.
19. The method of claim 18 , wherein the acetaminophen or the pharmaceutically acceptable salt thereof is present in an amount of about 290-360 mg.
20. The method of claim 19 , wherein the acetaminophen or the pharmaceutically acceptable salt thereof is present in an amount of about 325 mg.
21. The method of claim 1 , wherein the antiemetic is present in an amount of about 0.5 mg to about 60 mg.
22. The method of claim 1 or 21 , wherein the antiemetic is aprepitant, dronabinol, perphenazine, palonosetron, trimethyobenzamide, metoclopromide, domperidone, prochlorperazine, promethazine, chlorpromazine, trimethobenzamide, ondansetron, granisetron, hydroxyzine, acetylleucine monoethanolamine, alizapride, azasetron, benzquinamide, bietanautine, bromopride, buclizine, clebopride, cyclizine, dimenhydrinate, diphenidol, dolasetron, meclizine, methallatal, metopimazine, nabilone, oxyperndyl, pipamazine, scopolamine, sulpiride, tetrahydrocannabinol, thiethylperazine, thioproperazine, tropisetron, droperidol, haloperidol, prochloperazine, metoclopramide, diphenhydramine, cannabis, midazolam, lorazepam, hyoscine, dexamethasone, emetrol, propofol, or a pharmaceutically acceptable salt thereof.
23. The method of claim 21 , wherein the antiemetic is promethazine or a pharmaceutically acceptable salt thereof, and is present in an amount of about 12.5 mg, about 25 mg, or about 50 mg.
24. The method of claim 1 , wherein the non-opioid analgesic is present in an amount of about 200 mg to about 1000 mg.
25. The method of claim 24 , wherein the non-opioid analgesic is acetaminophen, ibuprofen, ketaprofen, naproxen, aspirin, or a pharmaceutically acceptable salt thereof.
26. The method of claim 1 , wherein the immediate-release matrix is a first layer and the controlled-release matrix is a second layer.
27. The method of any one of claim 1 - 17 , 18 - 20 , 21 , or 23 - 26 , wherein the solid oral pharmaceutical composition is a tablet.
28. The method of claim 27 , wherein the tablet has a thickness of about 6.5 mm or a hardness of about 15 kp.
29. The method of claim 27 , wherein the tablet is a bi-layer tablet.
30. The method of claim 1 , wherein the solid oral pharmaceutical composition provides an effective amount of the antiemetic to reduce or prevent nausea associated with the opioid analgesic or vomiting associated with the opioid analgesic for about 4 to about 6 hours, and an effective amount of the opioid analgesic and the non-opioid analgesic to treat pain for about 4 to about 6 hours.
31. The method of claim 1 , wherein the opioid analgesic is hydrocodone or a pharmaceutically acceptable salt thereof, wherein the non-opioid analgesic is acetaminophen or a pharmaceutically acceptable salt thereof, and wherein the antiemetic is promethazine or a pharmaceutically acceptable salt thereof.
32. The method of claim 7 , wherein the pharmaceutically acceptable salt of the hydrocodone is hydrocodone bitartrate, and is present in an amount of about 5 mg or about 10 mg.
33. The method of claim 1 , wherein the solid oral pharmaceutical composition further comprises an opioid antagonist or an abuse deterrent agent.