Multilayer Oral Tablets Containing a Non-Steroidal Anti-Inflammatory Drug and/or Acetaminophen

• US 20120064159A1
• Filed: 05/24/2010
• Published: 03/15/2012
• Est. Priority Date: 05/28/2009
• Status: Abandoned Application

• Current Assignee: Aptapharma, Inc.
• Original Assignee: Aptapharma, Inc.
• Inventors: Chauhan, Ishwar, Nutalapati, Siva Rama Krishna
• Application Number:
  US13/321,575
• Publication Number:
  US 20120064159A1
• Time in Patent Office: Days
• US Class Current: 424/465
• 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 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• 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 9/2068 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/2013
• 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 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

Multilayer tablets of a non-steroidal anti-inflammatory drug (NSAID) and/or acetaminophen for oral administration containing an immediate release layer or layers containing a NSAID and/or acetaminophen and/or a second therapeutic agent and an extended release layer containing a NSAID and/or acetaminophen are provided. Multilayer tablets containing an additional immediate and/or extended release layer of a second therapeutic agent are also provided. Methods for production of these multi-layer tablets and methods for their use in treating a subject in need of a NSAID and/or acetaminophen are also provided.

Claims

1. A multilayer tablet for oral administration comprising:

(a) an immediate release layer or layers comprising a non-steroidal anti-inflammatory drug (NSAID) and/or acetaminophen and a substituted alkylcellulose; and

(b) an extended release layer or layers comprising a NSAID and/or acetaminophen and a wax excipient.

2. The multilayer tablet of claim 1 wherein the extended release layer or layers does not comprise an acrylic polymer.

3. The multilayer tablet of claim 1 wherein the extended release layer or layers further comprises an alkylcellulose or a substituted alkylcellulose.

4. The multilayer tablet of claim 1 wherein the extended release layer or layers does not further comprise an alkylcellulose or a substituted alkylcellulose.

5. The multilayer tablet of claim 1 wherein the extended release layer or layers further comprises an organic acid present in a ratio of NSAID and/or acetaminophen to organic acid of from 50:

1 to 1;

50.

6. The multilayer tablet of claim 1 further comprising an immediate release layer and/or an extended release layer comprising a second therapeutic agent.

7. The multilayer tablet of claim 6 wherein the second therapeutic agent is a proton pump inhibitor.

8. The multilayer tablet of claim 1 further comprising an enteric coating or a polymer film coating.

9. The multilayer tablet of claim 8 further comprising a subcoating between the tablet and the enteric or polymer film coating.

17. A multilayer tablet of claim 1, wherein the NSAID and/or acetaminophen release rate from the tablet, when measured in vitro using a USP type II dissolution apparatus (paddle) in phosphate buffer at pH 6.8 and at 75 rotations per minute, corresponds to a dissolution pattern of:

a) from 20 to 70% of the total NSAID and/or acetaminophen is released after 1 hour of measurement in said apparatus;

b) not less than 50% of the total NSAID and/or acetaminophen is released after 3 hours of measurement in said apparatus; and

c) not less than 70% of the total NSAID and/or acetaminophen is released after a total of 6 hours of measurement in said apparatus.

18. A method for formulating the multilayer tablet of claim 1 comprising:

(a) preparing an immediate release tablet layer or layers comprising a NSAID and/or acetaminophen and a substituted alkylcellulose;

(b) preparing an extended release tablet layer or layers comprising a NSAID and/or acetaminophen and a wax excipient; and

(c) compressing together the immediate release tablet layer or layers and the extended release tablet layer or layers to form a multilayer tablet.

19. The method of claim 18 further comprising preparing an immediate release and/or extended release layer or layers comprising a second therapeutic agent and compressing together this layer or layers with the immediate release tablet layer or layers and the extended release tablet layer or layers of claim 18.

21. A method for treating a subject in need of a non-steroidal anti-inflammatory agent or acetaminophen comprising administering to the subject the multilayer tablet of claim 1.

10. A multilayer tablet for oral administration comprising:

(a) an extended release layer or layers comprising a NSAID and/or acetaminophen and a wax excipient; and

(b) an immediate release layer comprising a second therapeutic agent.

11. The multilayer tablet of claim 10 wherein the extended release layer or layers does not comprise an acrylic polymer.

12. The multilayer tablet of claim 10 wherein the extended release layer or layers further comprises an alkylcellulose or a substituted alkylcellulose.

13. The multilayer tablet of claim 10 wherein the extended release layer or layers does not further comprise an alkylcellulose or a substituted alkylcellulose.

14. The multilayer tablet of claim 10 wherein the second therapeutic agent is a proton pump inhibitor.

15. The multilayer tablet of claim 10 further comprising an enteric coating or a polymer film coating.

16. The multilayer tablet of claim 15 further comprising a subcoating between the tablet and the enteric or polymer film coating.

20. A method for formulating the multilayer tablet of claim 10 comprising:

(a) preparing an extended release tablet layer or layers comprising a NSAID and/or acetaminophen and a wax excipient;

(b) preparing an immediate release tablet layer or layers comprising a second therapeutic agent; and

(c) compressing together the immediate release tablet layer or layers and the extended release tablet layer or layers to form a multilayer tablet.

22. A multilayer tablet of claim 10, wherein the NSAID and/or acetaminophen release rate from the tablet, when measured in vitro using a USP type II dissolution apparatus (paddle) in phosphate buffer at pH 6.8 and at 75 rotations per minute, corresponds to a dissolution pattern of:

a) from 20 to 70% of the total NSAID and/or acetaminophen is released after 1 hour of measurement in said apparatus;

b) not less than 50% of the total NSAID and/or acetaminophen is released after 3 hours of measurement in said apparatus; and

c) not less than 70% of the total NSAID and/or acetaminophen is released after a total of 6 hours of measurement in said apparatus.

23. A method for treating a subject in need of a non-steroidal anti-inflammatory agent or acetaminophen comprising administering to the subject the multilayer tablet of claim 10.