Pharmaceutical compositions for treating or preventing pain

• US 8,728,522 B2
• Filed: 12/14/2010
• Issued: 05/20/2014
• Est. Priority Date: 07/08/2009
• Status: Active Grant

• Current Assignee: LOCL Pharma, Inc. (Charleston Laboratories, Inc.)
• Original Assignee: Charleston Laboratories, Inc.
• Inventors: Bosse, Paul, Ameling, John, Schachtel, Bernard, Takigiku, Ray
• Primary Examiner(s): ARNOLD, ERNST V
• Application Number:
  US12/967,423
• Publication Number:
  US 20110262539A1
• Time in Patent Office: 1,253 Days
• Field of Search: None
• US Class Current: 424/468
• 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 a subject, including reducing or eliminating an adverse effect associated with the analgesics.

Claims

1. A pharmaceutical composition in the form of a bi-layer tablet comprising:

(1) an immediate release layer comprising;

(a) about 5 mgs to about 20 mgs of promethazine or a pharmaceutically acceptable salt thereof,

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

(c) about 5 mgs to about 20 mgs of croscarmellose sodium, and

(d) about 0.2 mgs to about 5 mgs of magnesium stearate; and

(2) a controlled release layer comprising;

(a) about 250 mgs to about 400 mgs of acetaminophen, or a pharmaceutically acceptable salt thereof,

(b) about 2 mgs to about 15 mgs of hydrocodone, or a pharmaceutically acceptable salt thereof,

(c) about 100 mgs to about 250 mgs of silicified microcrystalline cellulose,

(d) about 5 mgs to about 30 mgs of hydroxypropyl methylcellulose,

(e) about 0.5 mgs to about 5 mgs of magnesium stearate, and

(f) about 0.5 mgs to about 10 mgs of stearic acid,

wherein the bi-layer tablet provides an effective amount of the hydrocodone and the acetaminophen, or pharmaceutically acceptable salts thereof, for about 4 to about 6 hours following administration, and provides an effective amount of the promethazine or pharmaceutically acceptable salt thereof to reduce or eliminate an adverse effect associated with administration of the hydrocodone or pharmaceutically acceptable salt thereof, and

wherein at least about 90% of the promethazine or pharmaceutically acceptable salt thereof is released within the first 10 minutes following administration, and 25% to 60% of the hydrocodone or pharmaceutically acceptable salt thereof is released within the first 5 minutes following administration.

2. The pharmaceutical composition of claim 1, wherein:

(1) the immediate release layer comprises;

(a) about 12.5 mgs of promethazine hydrochloride,

(b) about 121.5 mgs of silicified microcrystalline cellulose,

(c) about 15 mgs of croscarmellose sodium, and

(d) about 1 mg of magnesium stearate; and

(2) the controlled release layer comprises;

(a) about 325 mgs of acetaminophen,

(b) about 7.5 mgs of hydrocodone bitartrate,

(c) about 150 mgs of silicified microcrystalline cellulose,

(d) about 15.5 mgs of hydroxypropyl methylcellulose,

(e) about 2.75 mgs of magnesium stearate, and

(f) about 2.75 mgs of stearic acid.

3. The pharmaceutical composition of claim 1 or 2, wherein at least about 90% of the promethazine or pharmaceutically acceptable salt thereof is released within the first 5 minutes following administration.

4. The pharmaceutical composition of claim 1 or 2, wherein at least 80% of the acetaminophen or pharmaceutically acceptable salt thereof is released within the first 60 minutes following administration.

5. The pharmaceutical composition of claim 1 or 2, wherein less than about 80% of the hydrocodone or pharmaceutically acceptable salt thereof is released within the first 30 minutes following administration.

6. The pharmaceutical composition of claim 1 or 2, wherein the bi-layer tablet has a hardness of from about 7 to about 15 kp.

7. The pharmaceutical composition of claim 1 or 2, wherein the bi-layer tablet has a hardness of about 12 kp.

8. The pharmaceutical composition of claim 1 or 2, wherein the release rates are measured by chromatography.

9. The pharmaceutical composition of claim 1 or 2, wherein the controlled release layer further comprises about 0.1 mgs to about 20 mgs of croscarmellose sodium.

10. The pharmaceutical composition of claim 1 or 2, wherein the controlled release layer further comprises about 10 mgs of croscarmellose sodium.

11. The pharmaceutical composition of claim 1 or 2, wherein 35% to 70% of the acetaminophen or pharmaceutically acceptable salt thereof is released within the first 5 minutes following administration.

12. The pharmaceutical composition of claim 1 or 2, wherein about 90% to about 100% of the acetaminophen or pharmaceutically acceptable salt thereof and the hydrocodone or pharmaceutically acceptable salt thereof are released within the first 60 minutes following administration.

13. The pharmaceutical composition of claim 1 or 2, further comprising an effective amount of a stimulant, an opioid antagonist, an abuse deterrent agent, a barbiturate agent, or any combination thereof.

14. The pharmaceutical composition of claim 1, wherein the immediate release layer comprises about 12.5 mgs of promethazine hydrochloride.

15. The pharmaceutical composition of claim 1, wherein the controlled release layer comprises about 325 mgs of acetaminophen.

16. The pharmaceutical composition of claim 1, wherein the controlled release layer comprises about 7.5 mgs of hydrocodone bitartrate.

17. The pharmaceutical composition of claim 1 or 2, wherein the adverse effect associated with administration of the hydrocodone or pharmaceutically acceptable salt thereof is nausea, vomiting, constipation, itching, gastric upset, skin rash, or an allergic reaction.

27. The method of claim 10 or 26, wherein the controlled release layer of the bi-layer tablet further comprises about 0.1 mgs to about 20 mgs of croscarmellose sodium.

28. The method of claim 10 or 26, wherein the controlled release layer of the bi-layer tablet further comprises about 10 mgs of croscarmellose sodium.

18. A method of treating or preventing pain or discomfort in a subject in need thereof, comprising administering to the subject a pharmaceutical composition in the form of a bi-layer tablet which comprises:

(1) an immediate release layer comprising;

(a) about 5 mgs to about 20 mgs of promethazine or a pharmaceutically acceptable salt thereof,

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

(c) about 5 mgs to about 20 mgs of croscarmellose sodium, and

(d) about 0.2 mgs to about 5 mgs of magnesium stearate; and

(2) a controlled release layer comprising;

(a) about 250 mgs to about 400 mgs of acetaminophen, or a pharmaceutically acceptable salt thereof,

(b) about 2 mgs to about 15 mgs of hydrocodone, or a pharmaceutically acceptable salt thereof,

(c) about 100 mgs to about 250 mgs of silicified microcrystalline cellulose,

(d) about 5 mgs to about 30 mgs of hydroxypropyl methylcellulose,

(e) about 0.5 mgs to about 5 mgs of magnesium stearate, and

(f) about 0.5 mgs to about 10 mgs of stearic acid,

wherein the bi-layer tablet provides an effective amount of the hydrocodone and the acetaminophen, or pharmaceutically acceptable salts thereof, for about 4 to about 6 hours following administration, and provides an effective amount of the promethazine or pharmaceutically acceptable salt thereof to reduce or eliminate an adverse effect associated with administration of the hydrocodone or pharmaceutically acceptable salt thereof, and

wherein at least about 90% of the promethazine or pharmaceutically acceptable salt thereof is released within the first 10 minutes following administration, and 25% to 60% of the hydrocodone or pharmaceutically acceptable salt thereof is released within the first 5 minutes following administration.

19. The method of claim 18, wherein the subject experiences a reduction or elimination in nausea or vomiting associated with administration of the hydrocodone or pharmaceutically acceptable salt thereof.

20. The method of claim 18, wherein the adverse effect associated with administration of the hydrocodone or pharmaceutically acceptable salt thereof is nausea, vomiting, constipation, itching, gastric upset, skin rash, or an allergic reaction.

21. The method of claim 18, wherein the subject is 0-12 years old.

22. The method of claim 18, wherein the subject is about age 65 or older.

23. The method of claim 18, wherein the discomfort is a headache.

24. The method of claim 23, wherein the headache is a migraine headache, cluster headache, hemicrania continua headache, chronic headache, tension headache or chronic tension headache.

25. The method of claim 18, wherein the discomfort is photophobia.

26. The method of claim 18, wherein the bi-layer tablet comprises:

(1) the immediate release layer comprising;

(a) about 12.5 mgs of promethazine hydrochloride,

(b) about 121.5 mgs of silicified microcrystalline cellulose,

(c) about 15 mgs of croscarmellose sodium, and

(d) about 1 mg of magnesium stearate; and

(2) the controlled release layer comprising;

(a) about 325 mgs of acetaminophen,

(b) about 7.5 mgs of hydrocodone bitartrate,

(c) about 150 mgs of silicified microcrystalline cellulose,

(d) about 15.5 mgs of hydroxypropyl methylcellulose,

(e) about 2.75 mgs of magnesium stearate, and

(f) about 2.75 mgs of stearic acid.