Immediate Release Pharmaceutical Compositions with Abuse Deterrent Properties

• US 20130280176A1
• Filed: 04/18/2013
• Published: 10/24/2013
• Est. Priority Date: 04/18/2012
• Status: Abandoned Application

• Current Assignee: SpecGx LLC (Mallinckrodt plc)
• Original Assignee: Mallinckrodt LLC (Mallinckrodt plc)
• Inventors: Park, Jae Han, Raman, Siva N., Diezi, Thomas A.
• Application Number:
  US13/865,244
• Publication Number:
  US 20130280176A1
• Time in Patent Office: Days
• US Class Current: 424/44
• 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 31/485 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 9/0007 Effervescent A61K9/0065 takes precedence
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• 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 9/205 Polysaccharides, e.g. alginate, gums; Cyclodextrin
• CPC Class Codes: A61P 25/36 Opioid-abuse
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present disclosure provides pharmaceutical compositions and processes for making solid dosage form pharmaceutical compositions that provide immediate release of active ingredients and have abuse deterrent properties. The pharmaceutical compositions provided herein comprise at least one pharmaceutically active ingredient, at least one low molecular weight water-soluble polymer, at least one polyglycol, at least one polysaccharide, at least one clay mineral, and, optionally, an effervescent system.

Claims

1. A pharmaceutical composition comprising at least one active pharmaceutical ingredient (API) or a pharmaceutically acceptable salt thereof, at least one low molecular weight water-soluble polymer, at least one polyglycol, at least one polysaccharide, at least one clay mineral, and, optionally, an effervescent system.

2. The pharmaceutical composition of claim 1, wherein the low molecular weight water-soluble polymer has a molecular weight of no more than about 300,000 daltons;

the low molecular weight water-soluble polymer is chosen from a polyalkylene oxide, a cellulose ether, a polyolefinic alcohol, a polyvinyl lactam, a polycarboxylic acid, and combinations thereof; and

the low molecular weight water-soluble polymer is present in an amount from about 5% to about 60% by weight of the pharmaceutical composition.

3. The pharmaceutical composition of claim 1, wherein the polyglycol is chosen from a copolymer of ethylene glycol and propylene glycol, a polyethylene glycol, a polypropylene glycol, and combinations thereof;

and the polyglycol is present in an amount from about 5% to about 50% by weight of the pharmaceutical composition.

4. The pharmaceutical composition of claim 1, wherein the polysaccharide is a gum chosen from xanthan gum, acacia gum, diutan gum, gellan gum, guar gum, fenugreek gum, locust bean gum, pullulan, welan gum, and combinations thereof;

and the polysaccharide is present in an amount from about 1% to about 10% by weight of the pharmaceutical composition.

5. The pharmaceutical composition of claim 1, wherein the clay mineral is chosen from a bentonite, talc, and combinations thereof;

and the clay mineral is present in an amount from about 1% to about 30% by weight of the pharmaceutical composition.

6. The pharmaceutical composition of claim 1, wherein the effervescent system comprises a) an acid component chosen from an organic acid, an inorganic acid, and combinations thereof and b) a base component chosen from an alkali metal bicarbonate, an alkaline earth metal bicarbonate, an alkali metal carbonate, an organic carbonate, and combinations thereof;

and when the effervescent system is present in the pharmaceutical composition, it is present in an amount from about 5% to about 70% by weight of the pharmaceutical composition.

7. The pharmaceutical composition of claim 1, wherein the API is an opioid or a combination of an opioid and a non-opioid analgesic;

and the opioid is chosen from oxycodone, oxymorphone, hydrocodone, hydromorphone, codeine, and morphine.

8. The pharmaceutical composition of claim 1, further comprising a lubricant and, optionally, a superdisintegrant.

9. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is an oral solid dosage form.

10. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition releases at least about 70% of the API within about 45 minutes when measured using an USP-approved in vitro release procedure.

11. The pharmaceutical composition of claim 1, wherein when the pharmaceutical composition is milled for about 9 minutes to form particles, more than 30% of the particles have an average diameter of greater than about 250 microns.

12. The pharmaceutical composition of claim 1, wherein a viscous gel and/or colloidal dispersion is formed when the pharmaceutical composition is contacted with a small volume of an aqueous solvent.

13. The pharmaceutical composition of claim 1, wherein the low molecular weight water-soluble polymer is a polyethylene oxide having a molecular weight of about 100,000 daltons and is present in an amount from about 20% to about 50% by weight of the pharmaceutical composition;

the polyglycol is a copolymer of ethylene glycol and propylene glycol and is present in an amount from about 10% to about 45% by weight of the pharmaceutical composition;

the polysaccharide is xanthan gum and is present in an amount from about 2% to about 6% by weight of the pharmaceutical composition;

the clay mineral is sodium bentonite or a combination of sodium bentonite and talc and is present in an amount from about 5% to about 25% by weight of the pharmaceutical composition; and

the API is an opioid chosen from oxycodone, oxymorphone, hydrocodone, hydromorphone, codeine, and morphine.

14. The pharmaceutical composition of claim 14, further comprising the optional effervescent system comprising a) an acid component chosen from an organic acid, an inorganic acid, and combinations thereof and b) a base component chosen from an alkali metal bicarbonate, an alkaline earth metal bicarbonate, an alkali metal carbonate, an organic carbonate, and combinations thereof;

and the effervescent system is present in an amount from about 15% to about 50% by weight of the pharmaceutical composition.

15. A process for preparing a solid dosage form, the process comprising:

a) forming a mixture comprising at least one low molecular weight water-soluble polymer, at least one polyglycol, at least one polysaccharide, at least one clay mineral, and, optionally, an effervescent system;

b) forming the mixture into a solid dosage unit; and

c) heating the solid dosage unit to yield the solid dosage form.

16. The process of claim 16, wherein the low molecular weight water-soluble polymer has a molecular weight of no more than about 300,000 daltons and is chosen from a polyalkylene oxide, a cellulose ether, a polyolefinic alcohol, a polyvinyl lactam, a polycarboxylic acid, and combinations thereof;

the polyglycol is chosen from a copolymer of ethylene glycol and propylene glycol, a polyethylene glycol, a polypropylene glycol, and combinations thereof;

the polysaccharide is a gum chosen from xanthan gum, acacia gum, diutan gum, gellan gum, guar gum, fenugreek gum, locust bean gum, pullulan, welan gum, and combinations thereof;

the clay mineral is chosen from a bentonite, talc, and combinations thereof; and

the optional effervescent system comprises a) an acid component chosen from an organic acid, an inorganic acid, and combinations thereof and b) a base component chosen from an alkali metal bicarbonate, an alkaline earth metal bicarbonate, an alkali metal carbonate, an organic carbonate, and combinations thereof.

17. The process of claim 16, wherein the mixture formed in step (a) further comprises a lubricant and, optionally, a superdisintegrant.

18. The process of claim 16, wherein the mixture formed in step (a) further comprises at least one active pharmaceutical ingredient (API) or a pharmaceutically acceptable salt thereof.

19. The process of claim 18, wherein the API is an opioid or a combination of an opioid and a non-opioid analgesic;

and the opioid is chosen from oxycodone, oxymorphone, hydrocodone, hydromorphone, codeine, and morphine.

20. The process of claim 16, wherein the heating step (c) occurs at a temperature of less than about 90°

C.