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 tablet comprising two layers to a subject in need thereof, the tablet comprising:
a) a first layer formulated for controlled-release comprising an opioid analgesic and a non-opioid analgesic, wherein:
i) the opioid analgesic is oxycodone or a pharmaceutically acceptable salt thereof, or hydrocodone or a pharmaceutically acceptable salt thereof, 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, and
ii) the non-opioid analgesic is acetaminophen or a pharmaceutically acceptable salt thereof and is present in an amount of about 290-360 mg; and
b) a second layer formulated for immediate-release comprising an antiemetic, wherein the antiemetic is promethazine or a pharmaceutically acceptable salt thereof and is present in an amount of from about 12.5 mg to about 50 mg,
wherein the tablet comprises one or more excipients, wherein the one or more excipients comprise: carnauba wax, crospovidone, diacetylated monoglycerides, ethylcellulose, hydroxypropyl methylcellulose, hypromellose phthalate, magnesium stearate, mannitol, sodium hydroxide, sodium stearyl fumarate, talc, titanium dioxide, glyceryl monostearate 40-50, methacrylic acid copolymer type C, polysorbate 80, sugar spheres, triethyl citrate, microcrystalline cellulose, croscarmellose sodium, stearic acid, or yellow ferric oxide,
wherein the tablet demonstrates the following dissolution profile:
about 90% of the antiemetic is released in about 1 minute to about 20 minutes following contact of the tablet with a dissolution fluid as measured by USP Apparatus 2 (Paddle Apparatus), and
about 30% to about 60% of the opioid analgesic is released in 5 to 10 minutes following contact of the tablet with a dissolution fluid as measured by USP Apparatus 2 (Paddle Apparatus), and
wherein the tablet provides an effective amount of the promethazine or the pharmaceutically acceptable salt thereof to reduce or prevent nausea or vomiting associated with the opioid analgesic for about 4 to about 6 hours following administration to the subject and an effective amount of the oxycodone or the pharmaceutically acceptable salt thereof or the hydrocodone or the pharmaceutically acceptable salt thereof to treat pain for about 4 to about 6 hours following administration to the subject.
2. The method of claim 1 , wherein the opioid analgesic is hydrocodone bitartrate.
3. The method of claim 1 , wherein the opioid analgesic is hydrocodone or the pharmaceutically acceptable salt thereof, andis present in an amount of about 7.5 mg.
4. The method of claim 3 , wherein the pharmaceutically acceptable salt of the hydrocodone is hydrocodone bitartrate and is present in an amount of about 7.5 mg.
5. The method of claim 1 , wherein the opioid analgesic is hydrocodone or the pharmaceutically acceptable salt thereof, and is present in an amount of about 5 mg.
6. The method of claim 1 , wherein the opioid analgesic is oxycodone or the pharmaceutically acceptable salt thereof, and is present in an amount of about 7.5 mg.
7. The method of claim 1 , wherein the opioid analgesic is oxycodone or the pharmaceutically acceptable salt thereof, and is present in an amount of about 10 mg.
8. The method of claim 1 , wherein the opioid analgesic is oxycodone hydrochloride.
9. The method of claim 1 , wherein the promethazine or the pharmaceutically acceptable salt thereof is present in an amount of about 11-14 mg.
10. The method of claim 9 , wherein the promethazine or the pharmaceutically acceptable salt thereof is present in an amount of about 12.5 mg.
11. The method of claim 10 , wherein the pharmaceutically acceptable salt of the promethazine is promethazine hydrochloride and is present in an amount of about 12.5 mg.
12. The method of claim 9 , wherein the promethazine is present in an amount of about 11 mg.
13. The method of claim 1 , wherein the antiemetic is promethazine hydrochloride.
14. The method of claim 1 , wherein the tablet has a thickness of about 6.5 mm.
15. The method of claim 1 , wherein the tablet has a hardness of about 15 kp.
16. The method of claim 1 , wherein the opioid analgesic in the tablet is hydrocodone bitartrate that is present in an amount of about 7.5 mg, wherein the tablet comprises the pharmaceutically acceptable salt of the promethazine, wherein the pharmaceutically acceptable salt of the promethazine is promethazine hydrochloride that is present in an amount of about 12.5 mg, and wherein the tablet comprises about 325 mg of the acetaminophen.
17. The method of claim 1 , wherein the acetaminophen or the pharmaceutically acceptable salt thereof is present in an amount of about 325 mg.
18. The method of claim 1 , wherein about 90% to about 100% of the opioid analgesic or non-opioid analgesic is released in about 40 minutes following contact of the tablet with a dissolution fluid as measured by USP Apparatus 2 (Paddle Apparatus).
19. The method of claim 1 , wherein the tablet further comprises an opioid antagonist or abuse deterrent agent.