Pharmaceutical compositions

• US 8,124,126 B2
• Filed: 01/09/2009
• Issued: 02/28/2012
• Est. Priority Date: 01/09/2008
• 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): TRAN, SUSAN T
• Application Number:
  US12/351,704
• Publication Number:
  US 20090175939A1
• Time in Patent Office: 1,145 Days
• Field of Search: None
• US Class Current: 424/472
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• 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 31/24 having an amino or nitro group
• CPC Class Codes: A61K 31/403 condensed with carbocyclic rings, e.g. carbazole
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/422 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/515 Barbituric acids; Derivatives thereof, e.g. sodium pentobarbital
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 : Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2086 : Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• 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: A61K 9/4808 : characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/5084 : Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61P 1/08 : for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 : Antimigraine agents
• CPC Class Codes: A61P 25/08 : Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 29/02 : without antiinflammatory effect
• CPC Class Codes: A61P 39/00 : General protective or antinoxious agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system

Abstract

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.

Claims

1. A bi-layer tablet comprising:

(1) a controlled-release layer comprising (a) from about 6.5 mg to about 8.5 mg of hydrocodone or a pharmaceutically acceptable salt thereof, (b) from about 100 mg to about 170 mg of silicified microcrystalline cellulose, (c) from about 10 mg to about 20 mg of hydroxy propyl methyl cellulose, (d) from about 1 mg to about 4 mg of magnesium stearate, (e) from about 1 mg to about 4 mg of stearic acid, (f) about 290 mg to about 360 mg of acetaminophen or a pharmaceutically acceptable salt thereof; and

(2) an immediate release layer comprising (a) from about 11 mg to about 14 mg of promethazine or a pharmaceutically acceptable salt thereof, (b) from about 100 mg to about 140 mg of silicified microcrystalline cellulose, (c) from about 12 mg to about 18 mg of croscarmellose sodium and (d) from about 0.8 mg to about 1.5 mg of magnesium stearate,

wherein about 90% of the promethazine or a pharmaceutically acceptable salt thereof is released in about 1 minute to about 20 minutes following administration and about 100% of the promethazine or a pharmaceutically acceptable salt thereof is released in about 40 minutes following administration, wherein about 30% to about 60% of the hydrocodone or a pharmaceutically acceptable salt thereof and the acetaminophen or a pharmaceutically acceptable salt thereof are released within about 5 minutes to about 10 minutes following administration, wherein the bi-layer tablet provides an effective amount of promethazine, hydrocodone and acetaminophen or their pharmaceutically acceptable salts therof for about 4 hours to about 6 hours following administration, wherein said bi-layer tablet does not contain a NMDA receptor antagonist agent.

2. The bi-layer tablet of claim 1, wherein the composition further comprises a stimulant.

3. The bi-layer tablet of claim 2, wherein the stimulant is caffeine, modafinil or a pharmaceutically acceptable salt thereof.

4. The bi-layer tablet of claim 1, further comprising an opioid antagonist agent or abuse deterrent agent.

5. The bi-layer tablet of claim 1, wherein the opioid antagonist agent is nalmefene, naloxone, naltrexone, cyclazacine or levallorphan, or a pharmaceutically acceptable salt thereof.

6. The bi-layer tablet of claim 4, wherein the opioid antagonist agent is naltrexone or a pharmaceutically acceptable salt thereof.

7. The bi-layer tablet of claim 1, wherein the controlled-release layer comprises about 325 mg of acetaminophen or a pharmaceutically acceptable salt thereof.

8. The bi-layer tablet of claim 1, wherein the controlled-release layer comprises about 7.5 mg of hydrocodone or a pharmaceutically acceptable salt thereof.

9. The bi-layer tablet of claim 1, wherein the immediate release layer comprises about 12.5 mg of promethazine or a pharmaceutically acceptable salt thereof.

10. The bi-layer tablet of claim 1, wherein the bi-layer tablet has a thickness of about 6.5 mm.

11. The bi-layer tablet of claim 1, wherein the bi-layer tablet has a hardness of about 12.5 kilopond.

12. The bi-layer tablet of claim 11, wherein the bi-layer tablet has a thickness of about 6.5 mm.

13. The bi-layer tablet of claim 1, wherein about 90% to about 100% of the hydrocodone is released in about 40 minutes.

14. The bi-layer tablet of claim 1, wherein about 90% to about 100% of the acetaminophen is released in about 40 minutes.

15. The bi-layer tablet of claim 1, wherein at least about 90% of the promethazine, hydrocodone and acetaminophen dissolve in the stomach of a subject after about 45 minutes following administration.

16. The bi-layer tablet of claim 1, wherein said bi-layer tablet does not provide an effective amount of the hydrocodone or acetaminophen after 12 hours following administration.

17. A method for treating or preventing pain, comprising administering to a subject in need thereof a bi-layer tablet comprising:

(1) a controlled-release layer comprising (a) from about 6.5 mg to about 8.5 mg of hydrocodone or a pharmaceutically acceptable salt thereof, (b) from about 100 mg to about 170 mg of silicified microcrystalline cellulose, (c) from about 10 mg to about 20 mg of hydroxy propyl methyl cellulose, (d) from about 1 mg to about 4 mg of magnesium stearate, (e) from about 1 mg to about 4 mg of stearic acid, (f) from about 290 mg to about 360 mg of acetaminophen or a pharmaceutically acceptable salt thereof; and

(2) an immediate release layer comprising (a) from about 11 mg to about 14 mg of promethazine or a pharmaceutically acceptable salt thereof, (b) from about 100 mg to about 140 mg of silicified microcrystalline cellulose, (c) from about 12 mg to about 18 mg of croscarmellose sodium and (d) from about 0.8 mg to about 1.5 mg of magnesium stearate, wherein about 90% of the promethazine or a pharmaceutically acceptable salt thereof is released in about 1 minute to about 20 minutes following administration and about 100% of the promethazine or a pharmaceutically acceptable salt thereof is released in about 40 minutes following administration, wherein about 30% to about 60% of the hydrocodone or a pharmaceutically acceptable salt thereof and the acetaminophen or a pharmaceutically acceptable salt thereof are released in about 5 minutes to about 10 minutes following administration, wherein the bi-layer tablet provides an effective amount of promethazine, hydrocodone and acetaminophen or their pharmaceutically acceptable salts thereof, for about 4 hours to about 6 hours following administration, wherein said bi-layer tablet does not contain a NMDA receptor antagonist agent.

18. A method for treating or preventing a migraine headache comprising administering to a subject in need thereof a bi-layer tablet comprising:

(1) a controlled-release layer comprising (a) from about 6.5 mg to about 8.5 mg of hydrocodone or a pharmaceutically acceptable salt thereof, (b) from about 100 mg to about 170 mg of silicified microcrystalline cellulose, (c) from about 10 mg to about 20 mg of hydroxy propyl methyl cellulose, (d) from about 1 mg to about 4 mg of magnesium stearate, (e) from about 1 mg to about 4 mg of stearic acid, (f) from about 290 mg to about 360 mg of acetaminophen or a pharmaceutically acceptable salt thereof; and

(2) an immediate release layer comprising (a) from about 11 mg to about 14 mg of promethazine or a pharmaceutically acceptable salt thereof, (b) from about 100 mg to about 140 mg of silicified microcrystalline cellulose, (c) from about 12 mg to about 18 mg of croscarmellose sodium and (d) from about 0.8 mg to about 1.5 mg of magnesium stearate, wherein about 90% of the promethazine or a pharmaceutically acceptable salt thereof is released in about 1 minute to about 20 minutes following administration and about 100% of the promethazine or a pharmaceutically acceptable salt thereof is released in about 40 minutes following administration, wherein about 30% to about 60% of the hydrocodone or a pharmaceutically acceptable salt thereof and the acetaminophen or a pharmaceutically acceptable salt thereof are released in about 5 minutes to about 10 minutes following administration, wherein the bi-layer tablet provides an effective amount of promethazine, hydrocodone and acetaminophen or their pharmaceutically acceptable salts thereof, for about 4 hours to about 6 hours following administration, wherein said bi-layer tablet does not contain a NMDA receptor antagonist agent.

19. A method for treating or preventing a headache comprising administering to a subject in need thereof a bi-layer tablet comprising:

(1) a controlled-release layer comprising (a) from about 6.5 mg to about 8.5 mg of hydrocodone or a pharmaceutically acceptable salt thereof, (b) from about 100 mg to about 170 mg of silicified microcrystalline cellulose, (c) from about 10 mg to about 20 mg of hydroxy propyl methyl cellulose, (d) from about 1 mg to about 4 mg of magnesium stearate, (e) from about 1 mg to about 4 mg of stearic acid, (f) from about 290 mg to about 360 mg of acetaminophen or a pharmaceutically acceptable salt thereof; and

(2) an immediate release layer comprising (a) from about 11 mg to about 14 mg of promethazine or a pharmaceutically acceptable salt thereof, (b) from about 100 mg to about 140 mg of silicified microcrystalline cellulose, (c) from about 12 mg to about 18 mg of croscarmellose sodium and (d) from about 0.8 mg to about 1.5 mg of magnesium stearate, wherein about 90% of the promethazine or a pharmaceutically acceptable salt thereof is released in about 1 minute to about 20 minutes following administration and about 100% of the promethazine or a pharmaceutically acceptable salt thereof is released in about 40 minutes following administration, wherein about 30% to about 60% of the hydrocodone or a pharmaceutically acceptable salt thereof and the acetaminophen or a pharmaceutically acceptable salt thereof are released in about 5 minutes to about 10 minutes following administration, wherein the bi-layer tablet provides an effective amount of promethazine, hydrocodone and acetaminophen or their pharmaceutically acceptable salts thereof, for about 4 hours to about 6 hours following administration, wherein said bi-layer tablet does not contain a NMDA receptor antagonist agent.

20. The method of claim 19, wherein the headache is a migraine headache, cluster headache or hemicrania continua headache.

21. The method of claim 19, wherein the headache is a chronic headache, tension headache or chronic tension headache.

22. A method for treating pain, comprising administering to a subject in need thereof a bi-layer tablet comprising:

(1) a controlled-release layer comprising (a) from about 6.5 mg to about 8.5 mg of hydrocodone or a pharmaceutically acceptable salt thereof, (b) from about 100 mg to about 170 mg of silicified microcrystalline cellulose, (c) from about 10 mg to about 20 mg of hydroxy propyl methyl cellulose, (d) from about 1 mg to about 4 mg of magnesium stearate, (e) from about 1 mg to about 4 mg of stearic acid, (f) from about 290 mg to about 360 mg of acetaminophen or a pharmaceutically acceptable salt thereof; and

(2) an immediate release layer comprising (a) from about 11 mg to about 14 mg of promethazine or a pharmaceutically acceptable salt thereof, (b) from about 100 mg to about 140 mg of silicified microcrystalline cellulose, (c) from about 12 mg to about 18 mg of croscarmellose sodium and (d) from about 0.8 mg to about 1.5 mg of magnesium stearate, wherein about 90% of the promethazine or a pharmaceutically acceptable salt thereof is released in about 1 minute to about 20 minutes following administration and about 100% of the promethazine or a pharmaceutically acceptable salt thereof is released in about 40 minutes following administration, wherein about 30% to about 60% of the hydrocodone or a pharmaceutically acceptable salt thereof and the acetaminophen or a pharmaceutically acceptable salt thereof are released in about 5 minutes to about 10 minutes following administration, wherein the bi-layer tablet provides an effective amount of promethazine, hydrocodone and acetaminophen or their pharmaceutically acceptable salts thereof, for about 4 hours to about 6 hours following administration, wherein said bi-layer tablet does not contain a NMDA receptor antagonist agent;

wherein the subject is about 65 years of age or older.

23. A method for treating or preventing photophobia comprising administering to a subject in need thereof a bi-layer tablet comprising:

(1) a controlled-release layer comprising (a) from about 6.5 mg to about 8.5 mg of hydrocodone or a pharmaceutically acceptable salt thereof, (b) from about 100 mg to about 170 mg of silicified microcrystalline cellulose, (c) from about 10 mg to about 20 mg of hydroxy propyl methyl cellulose, (d) from about 1 mg to about 4 mg of magnesium stearate, (e) from about 1 mg to about 4 mg of stearic acid, (f) from about 290 mg to about 360 mg of acetaminophen or a pharmaceutically acceptable salt thereof; and

(2) an immediate release layer comprising (a) from about 11 mg to about 14 mg of promethazine or a pharmaceutically acceptable salt thereof, (b) from about 100 mg to about 140 mg of silicified microcrystalline cellulose, (c) from about 12 mg to about 18 mg of croscarmellose sodium and (d) from about 0.8 mg to about 1.5 mg of magnesium stearate, wherein about 90% of the promethazine or a pharmaceutically acceptable salt thereof is released in about 1 minute to about 20 minutes following administration and about 100% of the promethazine or a pharmaceutically acceptable salt thereof is released in about 40 minutes following administration, wherein about 30% to about 60% of the hydrocodone or a pharmaceutically acceptable salt thereof and the acetaminophen or a pharmaceutically acceptable salt thereof are released in about 5 to about 10 minutes following administration, wherein the bi-layer tablet provides an effective amount of promethazine, hydrocodone and acetaminophen or their pharmaceutically acceptable salts therof, for about 4 hours to about 6 hours following administration, wherein said bi-layer tablet does not contain a NMDA receptor antagonist agent.

24. The method of claim 23, wherein the photophobia is associated with migraine headache.