Gastric Retentive Extended-Release Dosage Forms Comprising Combinations of a Non-Opioid Analgesic and an Opioid Analgesic

• US 20100196474A1
• Filed: 12/22/2009
• Published: 08/05/2010
• Est. Priority Date: 03/11/2008
• Status: Active Grant

• Current Assignee: Assertio Therapeutics, Inc. (Assertio Holdings, Inc.)
• Original Assignee: Depomed Incorporated (Assertio Holdings, Inc.)
• Inventors: Han, Chien-Hsuan, Hou, Sui Yuen Eddie, Reid, Monica L.
• Granted Patent: US 8,372,432 B2
• Time in Patent Office: Days
• US Class Current: 424/469
• 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 31/4355 the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0065 Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
• CPC Class Codes: A61K 9/0087 Galenical forms not covered by A61K9/02 - A61K9/7023
• 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 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

Compositions and methods for the treatment of pain in a mammal are described. More specifically, a dosage form designed for release of acetaminophen and an opioid is described, wherein the dosage form provides delivery of the drugs to the upper gastrointestinal tract (“GI”) of a mammal for an extended period of time.

Claims

1. A dosage form for extended release of an opioid and acetaminophen, comprising:

an extended release portion comprising a first dose of acetaminophen and a first dose of an opioid dispersed in a polymer matrix comprised of at least one hydrophilic polymer that swells upon imbibition of fluid to a size sufficient for gastric retention in a gastrointestinal tract of a subject in a fed mode, said first dose of acetaminophen released from the dosage form through erosion of the polymer matrix, and said first dose of opioid released from the dosage form at a rate proportional to release of the acetaminophen during a period of gastric retention of between about 4 to about 8 hours.

2. The dosage form of claim 1, wherein the first dose of acetaminophen is approximately 275-325 mg and the first dose of the opioid is approximately 14-20 mg.

3. The dosage form of claim 1, wherein the opioid is selected from the group consisting of tramadol, oxycodone, hydromorphone, codeine and hydrocodone.

4. The dosage form of claim 1, wherein the polymer is a poly(ethylene oxide) having a molecular weight of between about 500,000 Daltons to about 10,000,000 Daltons.

5. The dosage form of claim 1, wherein the polymer is present in an amount ranging from about 35 to about 50 weight percent of the extended release portion.

6. The dosage form of claim 1, wherein the extended release portion comprises particles of the opioid granulated with a binder and a filler.

7. The dosage form of claim 6, wherein the particles have an average particle size greater than about 20 microns and less than about 2000 microns.

8. The dosage form of claim 1, further comprising an immediate release portion comprising a second dose of acetaminophen and a second dose of the opioid, said immediate release portion in contact with said extended release portion.

9. The dosage form of claim 8, wherein the second dose of acetaminophen is approximately 175 mg to 240 mg and the second dose of the opioid is approximately 10 mg to 20 mg.

10. The dosage form of claim 8, wherein the immediate release portion of the dosage form and the extended release portion of the dosage form comprise a bilayer tablet.

11. The dosage form of claim 10, wherein said tablet has a hardness of about 12 Kp to about 20 Kp.

12. The dosage form of claim 10, wherein said tablet has a friability of less than about 1.0%.

13. The dosage form of claim 10, wherein the tablets have a content uniformity of from about 85 to about 115 percent by weight and a relative standard deviation (RSD) of not more than 6 percent.

14. The dosage form of claim 10, wherein upon administration of the tablet to a subject, the tablet imbibes fluid and swells to a size between about 120% to about 140% of the dosage farms size prior to administration within 1 hour after administration.

15. The dosage form of claim 10, wherein between about 40% to about 60% of the acetaminophen and between about 50% to about 70% of the opioid is released within about 1 hour in an in vitro dissolution test.

16. A method for treating a subject suffering from pain, comprising orally administering to said subject the dosage form of claim 1.

17. The method of claim 21, wherein said administering comprises administering twice in a 24-hour period, and wherein said administering is with a meal.

18. A dosage form for release of acetaminophen and an opioid, comprising,

an immediate release component and an extended release component, each of said components comprising acetaminophen and an opioid, said dosage form having an in vitro dissolution release rate of acetaminophen, when measured using a USP disintegration tester with 800 mL aqueous buffer at pH 1.2 at 37°

C., from about 40-65% acetaminophen released after 1 hour, from 55-80% acetaminophen released after 2 hours and at least about 75% acetaminophen released after 6 hours.

19. The dosage form of claim 23, wherein release of acetaminophen and opioid from the extended release component is achieved by a combination of erosion of the extended release component and diffusion of one or both of the drugs.