Pharmaceutical compositions for treating or preventing pain

• US 10,016,368 B2
• Filed: 11/08/2016
• Issued: 07/10/2018
• Est. Priority Date: 07/08/2009
• Status: Active Grant

• Current Assignee: LOCL Pharma, Inc. (Charleston Laboratories, Inc.)
• Original Assignee: LOCL Pharma, Inc. (Charleston Laboratories, Inc.)
• Inventors: Bosse, Paul, Ameling, John, Schachtel, Bernard, Takigiku, Ray
• Primary Examiner(s): Arnold, Ernst V
• Application Number:
  US15/346,541
• Publication Number:
  US 20170049704A1
• Time in Patent Office: 609 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

Methods and compositions are provided which comprise effective amounts of one or more analgesics, such as hydrocodone or acetaminophen, and an antiemetic, such as promethazine, to treat or prevent pain in a subject, and to reduce or prevent an adverse effect associated with the analgesics.

Claims

1. A solid oral pharmaceutical composition, wherein the solid oral pharmaceutical composition comprises:

(1) a first layer that comprises;

(a) 5 mg to 30 mg of an antiemetic,

(b) about 75 mg to about 150 mg of silicified microcrystalline cellulose,

(c) about 10 mg to about 20 mg of croscarmellose sodium, and

(d) about 0.5 mg to 2 mg of magnesium stearate; and

(2) a second layer that comprises;

(a) about 0.5 mg to about 20 mg of an opioid analgesic,

(b) about 75 mg to about 250 mg of silicified microcrystalline cellulose,

(c) about 10 mg to about 40 mg of hydroxy methyl propyl cellulose,

(d) about 0.5 mg to 5 mg of magnesium stearate, and

(e) about 0.5 mg to about 5 mg of stearic acid.

2. The solid oral pharmaceutical composition of claim 1, wherein at least two antiemetics are present in the first layer.

3. The solid oral pharmaceutical composition of claim 1, wherein the antiemetic comprises promethazine or a pharmaceutically acceptable salt thereof, ondansetron or a pharmaceutically acceptable salt thereof, or a combination thereof.

4. The solid oral pharmaceutical composition of claim 3, wherein the antiemetic is promethazine or a pharmaceutically acceptable salt thereof.

5. The solid oral pharmaceutical composition of claim 3, wherein the antiemetic comprises the pharmaceutically acceptable salt of promethazine that is promethazine hydrochloride.

6. The solid oral pharmaceutical composition of claim 3, wherein the promethazine or the pharmaceutically acceptable salt thereof is present in an amount from 5 mg to 13 mg.

7. The solid oral pharmaceutical composition of claim 3, wherein the promethazine or the pharmaceutically acceptable salt thereof is present in an amount from about 10 mg to about 15 mg.

8. The solid oral pharmaceutical composition of claim 3, wherein the promethazine or the pharmaceutically acceptable salt thereof is present in an amount of about 12.5 mg.

9. The solid oral pharmaceutical composition of claim 3, wherein the promethazine is present in an amount of about 11 mg.

10. The solid oral pharmaceutical composition of claim 1, wherein the opioid analgesic comprises oxycodone or a pharmaceutically acceptable salt thereof.

11. The solid oral pharmaceutical composition of claim 1, wherein the opioid analgesic comprises hydrocodone or a pharmaceutically acceptable salt thereof.

12. The solid oral pharmaceutical composition of claim 11, wherein the hydrocodone or the pharmaceutically acceptable salt thereof is present in an amount from about 1 mg to about 15 mg.

13. The solid oral pharmaceutical composition of claim 1, wherein:

the antiemetic is promethazine or a pharmaceutically acceptable salt thereof; and

the opioid analgesic is oxycodone or a pharmaceutically acceptable salt thereof.

14. The solid oral pharmaceutical composition of claim 13, wherein:

the antiemetic is the pharmaceutically acceptable salt of promethazine that is promethazine hydrochloride present in an amount of about 12.5 mg; and

the opioid analgesic is the pharmaceutically acceptable salt of oxycodone that is oxycodone hydrochloride present in an amount of about 5 mg.

15. The solid oral pharmaceutical composition of claim 1, wherein the second layer further comprises about 200 mg to about 1000 mg of a non-opioid analgesic.

16. The solid oral pharmaceutical composition of claim 15, wherein the non-opioid analgesic comprises acetaminophen or a pharmaceutically acceptable salt thereof.

17. The solid oral pharmaceutical composition of claim 1, wherein the solid oral pharmaceutical composition further comprises an effective amount of an abuse deterrent agent.

18. A method for treating or preventing pain, and reducing or preventing an adverse effect associated with an opioid analgesic, comprising administering to a subject in need thereof the solid oral pharmaceutical composition of claim 1, wherein the solid oral pharmaceutical composition provides an effective amount of the opioid analgesic to treat or prevent pain in the subject in need thereof, and an effective amount of the antiemetic to reduce or prevent an adverse effect associated with the opioid analgesic in the subject in need thereof.

19. The method of claim 18, wherein the method treats pain and reduces nausea or vomiting associated with the opioid analgesic.

20. The method of claim 18, wherein the administration to the subject in need thereof occurs at about every 4 to 6 hours.

21. The method of claim 18, wherein at least two antiemetics are present in the first layer.

22. The method of claim 18, wherein the antiemetic comprises promethazine or a pharmaceutically acceptable salt thereof, ondansetron or a pharmaceutically acceptable salt thereof, or a combination thereof.

23. The method of claim 22, wherein the antiemetic is promethazine or a pharmaceutically acceptable salt thereof.

24. The method of claim 22, wherein the antiemetic comprises the pharmaceutically acceptable salt of promethazine that is promethazine hydrochloride.

25. The method of claim 22, wherein the promethazine or the pharmaceutically acceptable salt thereof is present in an amount from 5 mg to 13 mg.

26. The method of claim 22, wherein the promethazine or the pharmaceutically acceptable salt thereof is present in an amount from about 10 mg to about 15 mg.

27. The method of claim 22, wherein the promethazine or the pharmaceutically acceptable salt thereof is present in an amount of about 12.5 mg.

28. The method of claim 22, wherein the promethazine is present in an amount of about 11 mg.

29. The method of claim 18, wherein the opioid analgesic comprises oxycodone or a pharmaceutically acceptable salt thereof.

30. The method of claim 18, wherein the opioid analgesic comprises hydrocodone or a pharmaceutically acceptable salt thereof.

31. The method of claim 30, wherein the hydrocodone or the pharmaceutically acceptable salt thereof is present in an amount from about 1 mg to about 15 mg.

32. The method of claim 18, wherein:

the antiemetic is promethazine or a pharmaceutically acceptable salt thereof; and

the opioid analgesic is oxycodone or a pharmaceutically acceptable salt thereof.

33. The method of claim 32, wherein:

the antiemetic is the pharmaceutically acceptable salt of promethazine that is promethazine hydrochloride present in an amount of about 12.5 mg; and

the opioid analgesic is the pharmaceutically acceptable salt of oxycodone that is oxycodone hydrochloride present in an amount of about 5 mg.

34. The method of claim 18, wherein the second layer further comprises about 200 mg to about 1000 mg of a non-opioid analgesic.

35. The method of claim 34, wherein the non-opioid analgesic comprises acetaminophen or a pharmaceutically acceptable salt thereof.

36. The method of claim 18, wherein the solid oral pharmaceutical composition further comprises an effective amount of an abuse deterrent agent.