Pharmaceutical compositions

• US 8,653,066 B2
• Filed: 10/09/2007
• Issued: 02/18/2014
• Est. Priority Date: 10/09/2006
• Status: Active Grant

• Current Assignee: LOCL Pharma, Inc. (Charleston Laboratories, Inc.)
• Original Assignee: Charleston Laboratories, Inc.
• Inventors: Bosse, Paul
• Primary Examiner(s): JEAN-LOUIS, SAMIRA JM
• Application Number:
  US12/444,521
• Publication Number:
  US 20100143469A1
• Time in Patent Office: 2,324 Days
• Field of Search: 514/226.2, 424/472
• US Class Current: 514/226.2
• 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 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• 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: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• 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 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents

Abstract

Pharmaceutical compositions are provided which comprise effective amounts of analgesic to treat a subject, including to reduce or eliminate an adverse effect associated with the analgesic.

Claims

1. A bi-layer tablet comprising (a) an immediate-release layer that comprises promethazine or a pharmaceutically acceptable salt thereof;

and (b) a controlled-release layer that comprises an opioid analgesic agent and a non-opioid analgesic agent, wherein the non-opioid analgesic agent is acetaminophen or a pharmaceutically acceptable salt thereof, wherein the opioid analgesic agent is hydrocodone, oxycodone, or a pharmaceutically acceptable salt thereof, 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 within about 1 hour following administration, and wherein the hydrocodone, oxycodone, or a pharmaceutically acceptable salt thereof, is released within about 20 minutes to about 180 minutes following administration.

2. The bi-layer tablet of claim 1, wherein the opioid analgesic agent is hydrocodone bitartrate or oxycodone hydrochloride.

3. The bi-layer tablet of claim 1, comprising from 1% to 20% by weight of the promethazine or a pharmaceutically acceptable salt thereof;

from 10% to 80% by weight of the acetaminophen or a pharmaceutically acceptable salt thereof; and

from 1% to 20% by weight of the hydrocodone, oxycodone, or a pharmaceutically acceptable salt thereof.

6. The bi-layer tablet of claim 1, wherein the opioid analgesic agent is the hydrocodone or a pharmaceutically acceptable salt thereof.

7. The bi-layer tablet of claim 1, wherein the opioid analgesic agent is the oxycodone or a pharmaceutically acceptable salt thereof.

8. The bi-layer tablet of claim 1, comprising from 5 to 13 mg of the promethazine or a pharmaceutically acceptable salt thereof, from 310 to 330 mg of the acetaminophen or a pharmaceutically acceptable salt thereof, and from 6 to 8 mg of the hydrocodone or a pharmaceutically acceptable salt thereof.

9. The bi-layer tablet of claim 1, comprising about 12.5 mg of the promethazine or a pharmaceutically acceptable salt thereof, about 325 mg of the acetaminophen or a pharmaceutically acceptable salt thereof, and about 7.5 mg of the hydrocodone or a pharmaceutically acceptable salt thereof.

10. The bi-layer tablet of claim 1, comprising the promethazine or a pharmaceutically acceptable salt thereof, the acetaminophen or a pharmaceutically acceptable salt thereof, and the hydrocodone or a pharmaceutically acceptable salt thereof in a mass ratio of about (1 to 2):

(40 to

     45);

(1 to

     2).

11. The bi-layer tablet of claim 1, comprising the promethazine or a pharmaceutically acceptable salt thereof, the acetaminophen or a pharmaceutically acceptable salt thereof, and the hydrocodone or a pharmaceutically acceptable salt thereof in a mass ratio of about (1.67):

(43.33);

(1).

12. The bi-layer tablet of claim 1, further comprising an opioid antagonist or an additional agent for reducing abuse and/or diversion.

13. The bi-layer tablet of claim 12, wherein the opioid antagonist is nalmefene, naloxone, or naltrexone.

4. A method for alleviating an adverse effect associated with administration of an opioid analgesic agent to a subject, the method comprising administering to the subject a bi-layer tablet comprising:

(a) an immediate-release layer that comprises promethazine or a pharmaceutically acceptable salt thereof; and

(b) a controlled-release layer that comprises the opioid analgesic agent and a non-opioid analgesic agent, wherein the non-opioid analgesic agent is acetaminophen or a pharmaceutically acceptable salt thereof, wherein the opioid analgesic agent is hydrocodone, oxycodone, or a pharmaceutically acceptable salt thereof, 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 within about 1 hour following administration, and wherein the hydrocodone, oxycodone, or a pharmaceutically acceptable salt thereof, is released within about 20 minutes to about 180 minutes following administration.

5. A method for treating pain in a subject suffering from or susceptible to pain, the method comprising administering to the subject a bi-layer tablet comprising:

(a) an immediate-release layer that comprises promethazine or a pharmaceutically acceptable salt thereof; and

(b) a controlled-release layer that comprises an opioid analgesic agent and a non-opioid analgesic agent, wherein the non-opioid analgesic agent is acetaminophen or a pharmaceutically acceptable salt thereof, wherein the opioid analgesic agent is hydrocodone, oxycodone, or a pharmaceutically acceptable salt thereof, 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 within about 1 hour following administration, and wherein the hydrocodone, oxycodone, or a pharmaceutically acceptable salt thereof, is released within about 20 minutes to about 180 minutes following administration.