ORAL CONTROLLED RELEASE TABLET

• US 20090208572A1
• Filed: 02/17/2009
• Published: 08/20/2009
• Est. Priority Date: 02/15/2008
• Status: Abandoned Application

• Current Assignee: Sun Pharma Advanced Research Company Limited (Shanghvi Finance Pvt Ltd.)
• Original Assignee: Sun Pharma Advanced Research Company Limited (Shanghvi Finance Pvt Ltd.)
• Inventors: Dharmadhikari, Nitin Bhalachandra, Zala, Yashoraj Rupsinh
• Application Number:
  US12/372,161
• Publication Number:
  US 20090208572A1
• Time in Patent Office: Days
• US Class Current: 424/472
• 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 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Abstract

A method of reducing the risk of alcohol-induced dose-dumping of a therapeutically active ingredient comprising administering to human subjects who have ingested alcohol an oral controlled release tablet; said tablet comprising:

• • a core comprising
    • an upper compressed layer comprising a swelling agent, and
    • a lower compressed layer comprising at least one therapeutically active ingredient, and pharmaceutically acceptable excipient wherein at least one excipient is a release rate controlling excipient and wherein the percent by weight of excipients that are soluble in alcohol does not exceed 35% by weight of the layer and;
  • a coating surrounding the said core, the coating comprising a polymer insoluble in an aqueous medium comprising from 0% v/v to 40% v/v of alcohol, whereby upon contact with aqueous gastrointestinal fluids, the upper compressed layer swells to cause removal of the coating from the upper surface of the upper compressed layer and then said upper layer disintegrates allowing the release of the active ingredient from the defined surface area of the upper surface of said lower compressed layer with the coating covering its bottom and side surfaces.

Claims

1. A method of reducing the risk of alcohol-induced dose-dumping of a therapeutically active ingredient comprising administering to human subjects who have ingested alcohol an oral controlled release tablet;

said tablet comprising;

a core comprising

an upper compressed layer comprising a swelling agent, and

a lower compressed layer comprising at least one therapeutically active ingredient, and pharmaceutically acceptable excipient wherein at least one excipient is a release rate controlling excipient and wherein the percent by weight of excipients that are soluble in alcohol does not exceed 35% by weight of the layer and;

a coating surrounding the said core, the coating comprising a polymer insoluble in an aqueous medium comprising from 0% v/v to 40% v/v of alcohol,

whereby upon contact with aqueous gastrointestinal fluids, the upper compressed layer swells to cause removal of the coating from the upper surface of the upper compressed layer and then said upper layer disintegrates allowing the release of the active ingredient from the defined surface area of the upper surface of said lower compressed layer with the coating covering its bottom and side surfaces.

4. A method as claimed in claim 1 wherein the wicking agent in present in amounts ranging from about 5% to about 80% by weight of the upper compressed layer.

6. A method as claimed in claim 1 wherein the super-disintegrant is present in amount ranging from about 5% to about 30% by weight of the upper compressed layer.

8. A method as claimed in claim 1 or claim 2 wherein the coating is impermeable or semi-permeable to the therapeutically active ingredient.

9. A method as claimed in claim 1 or claim 2 wherein the coating comprises one or more leachable component.

10. A method as claimed in claim 1 or claim 2 the coating has one or more pre formed passageways located in the immediate vicinity of the compressed layer comprising swelling agent.

11. A method as claimed in claim 1 or claim 2 wherein the total amount of excipients that are soluble in alcohol does not exceed 25% by weight of the lower compressed layer.

12. A method as claimed in claim 1 wherein the total amount of excipients that are soluble in alcohol does not exceed 25% by weight of the middle compressed layer.

13. A method as claimed in claim 1 or claim 2 wherein the oral controlled release tablet does not release more than 80% of the active ingredient in about 4 hours when tested in vitro in 40% v/v ethanol.

14. A method as claimed in claim 1 or claim 2 the oral controlled release tablet does not release more than 40% of the active ingredient in about 2 hours when tested in vitro in 40% v/v ethanol.

15. A method as claimed in claim 1 or claim 2 wherein polymer insoluble in an aqueous medium of 0% v/v to 40% v/v of alcohol content is ethyl cellulose.

16. A method as claimed in claim 1 or claim 2 wherein the ethyl cellulose has ethoxy content is more than 46.5%.

17. A method as claimed in claim 1 or claim 2 wherein the ethyl cellulose has ethoxy content ranging from about 48% to about 49.5%.

2. A method of reducing the risk of alcohol-induced dose-dumping of a therapeutically active ingredient comprising administering to human subjects who have ingested alcohol an oral controlled release tablet;

said tablet comprising;

a core comprising

an upper compressed layer comprising a swelling agent, and

a middle compressed layer comprising at least one therapeutically active ingredient, and pharmaceutically acceptable excipient wherein at least one excipient is a release rate controlling excipient and wherein the total amount of excipients that are soluble in alcohol does not exceed 35% by weight of the layer and;

a bottom compressed layer comprising a swelling agent,

a coating surrounding the said core, the coating comprising a polymer insoluble in an aqueous medium comprising from 0% v/v to 40% v/v of alcohol content,

whereby upon contact with aqueous gastrointestinal fluids, the upper compressed layer and the bottom compressed layer swell to cause removal of the coating from the upper surface of the upper compressed layer and the lower surface of the bottom compressed layer and then said upper layer and the said bottom layer disintegrate, allowing the release of the active ingredient from the defined surface area of the upper and lower surface of said middle compressed layer with the coating covering its side surfaces.

5. A method as claimed in claim 2 wherein the wicking agent in present in amounts ranging from about 5% to about 80% by weight of the upper and bottom compressed layers.

7. A method as claimed in claim 2 wherein the super-disintegrant is present in amount ranging from about 5% to about 30% by weight of the upper and lower compressed layers.

3. A method as claimed in 1 or 2 wherein the swelling agent is selected from the group comprising super-disintegrants, wicking agents, osmogents, gas generating agents and mixtures thereof.