GASTRIC RETENTIVE PHARMACEUTICAL COMPOSITIONS FOR IMMEDIATE AND EXTENDED RELEASE OF ACETAMINOPHEN

• US 20110052685A1
• Filed: 08/31/2010
• Published: 03/03/2011
• Est. Priority Date: 08/31/2009
• Status: Abandoned Application

• Current Assignee: Assertio Therapeutics, Inc. (Assertio Holdings, Inc.)
• Original Assignee: Depomed Incorporated (Assertio Holdings, Inc.)
• Inventors: Vargas, Thadd, Hou, Sui Yuen Eddie
• Application Number:
  US12/872,723
• Publication Number:
  US 20110052685A1
• Time in Patent Office: Days
• US Class Current: 424/468
• 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 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 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• 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 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• 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

Abstract

Gastric retentive dosage forms for extended release of acetaminophen or for both immediate and extended release of acetaminophen are described. The dosage forms allow effective pain relief upon once- or twice-daily dosing. Methods of treatment using the dosage forms and methods of making the dosage forms are also described.

Claims

1. A gastric retentive dosage form, comprising:

a extended release (ER) layer comprising a first dose of acetaminophen dispersed in a polymeric matrix wherein the polymeric matrix is comprised of at least one polymer that upon imbibition of fluid swells to a size sufficient for gastric retention, and

wherein the first dose of acetaminophen is released over a time period of about 8 to 9 hours in vitro.

2. The dosage form of claim 1, further comprising an IR layer, wherein the IR layer comprises a second dose of acetaminophen.

3. The dosage form of claim 1, wherein the first dose of acetaminophen ranges from about 500 mg to about 1000 mg acetaminophen.

4. The dosage form of claim 2, wherein the second dose of acetaminophen ranges from about 100 mg to about 500 mg acetaminophen.

5. The dosage form of claim 1, wherein the dosage form is a tablet, and wherein the total weight of the tablet ranges from about 500 mg to about 1400 mg.

6. The dosage form of claim 1, wherein the at least one polymer is poly(ethylene oxide) or hydroxypropyl methylcellulose.

7. The dosage form of claim 1, wherein the at least one polymer is a poly(ethylene oxide) having an average molecular weight ranging from about 200,000 Da, to 10,000,000 Da.

8. The dosage form of claim 1, wherein the ratio of acetaminophen to hydrophilic polymer in the ER layer ranges from about 1.5:

1 to about 35;

1.

9. The dosage form of claim 1, wherein at least 90% of the first dose of acetaminophen is released from the ER layer over a time period of 6 to 12 hours.

10. The dosage form of claim 1, wherein the dosage form is a tablet and wherein the tablet has a hardness of at least 15 kilopond (kp).

11. The dosage form of claim 1, wherein the ER layer swells upon ingestion to a size that is at least about 25% greater than the size of the dosage form prior to imbibition of fluid.

12. A method for making a tablet comprising an extended release (ER) layer comprising a first dose of acetaminophen dispersed in a polymeric matrix,

wherein making the ER layer comprises granulating acetaminophen powder with at least one hydrophilic polymer, or compressing the at least one hydrophilic polymer with a pregranulated acetaminophen composition.

13. The method of claim 12, wherein the granulating acetaminophen powder with at least one hydrophilic polymer comprises granulating the acetaminophen powder with a starch and/or povidone.

14. A method for treating a subject diagnosed with or suffering from a pain state comprising administering a gastric retentive dosage form, comprising:

an ER layer comprising a first dose of acetaminophen dispersed in a polymeric matrix wherein the polymeric matrix is comprised of at least one polymer that upon imbibition of fluid swells to a size sufficient for gastric retention, and

wherein the first dose of acetaminophen is released over a time period of about 8 to 9 hours in vitro;

wherein the subject is in a fed mode.

15. The method of claim 14, wherein the dose form further comprises an IR layer, wherein the IR layer comprises a second dose of acetaminophen.

16. The method of claim 14, wherein the administering is once per 24 hour period.

17. The method of claim 14, wherein the administering is twice per 24 hour period.

18. The method of claim 14, wherein the pain state is chronic and/or acute pain.