Immediate Release, Abuse Deterrent Pharmaceutical Compositions

• US 20130280177A1
• Filed: 04/18/2013
• Published: 10/24/2013
• Est. Priority Date: 04/18/2012
• Status: Active Grant

• Current Assignee: SpecGx LLC (Mallinckrodt plc)
• Original Assignee: Mallinckrodt LLC (Mallinckrodt plc)
• Inventors: Raman, Siva N., Park, Jae Han, Diezi, Thomas A., Herman, Clifford J.
• Granted Patent: US 9,993,422 B2
• 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 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61P 25/36 Opioid-abuse

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 hydrophilic polymer, at least one high molecular weight hydrophilic polymer, and 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 hydrophilic polymer, at least one high molecular weight hydrophilic polymer, and an effervescent system.

2. The pharmaceutical composition of claim 1, wherein the low molecular weight hydrophilic polymer has an average molecular weight of no more than about 200,000 Daltons;

the low molecular weight hydrophilic polymer is chosen from a polyalkylene oxide, a cellulose ether, a polyalkylene glycol, a Poloxamer, and combinations thereof; and

the low molecular weight hydrophilic polymer is present in an amount from about 5% to about 50% by weight of the pharmaceutical composition.

3. The pharmaceutical composition of claim 1, wherein the high molecular weight hydrophilic polymer has an average molecular weight of at least about 400,000 Daltons;

the high molecular weight hydrophilic polymer is chosen from a polyalkylene oxide, a cellulose ether, a polysaccharide, and combinations thereof; and

the high molecular weight hydrophilic polymer is present in an amount from about 0.1% to about 30% by weight of the pharmaceutical composition.

4. The pharmaceutical composition of claim 1, wherein the effervescent system comprises an a) 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 20% to about 90% by weight of the pharmaceutical composition.

5. 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.

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

7. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition has a hardness of at least about 10 kilopond.

8. The pharmaceutical composition of claim 1, wherein when the pharmaceutical composition is milled for about 6 minutes to form particles, more than 30% of the particles have an average diameter of greater than about 250 microns.

9. 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.

10. The pharmaceutical composition of claim 1, wherein the low molecular weight hydrophilic polymer has an average molecular weight of no more than about 200,000 Daltons;

the low molecular weight hydrophilic polymer is chosen from polyethylene oxide, hydroxypropylmethyl cellulose, sodium carboxymethyl cellulose, polyethylene glycol, a Poloxamer, and combinations thereof;

the low molecular weight hydrophilic polymer is present in an amount from about 20% to about 35% by weight of the pharmaceutical composition;

the high molecular weight hydrophilic polymer has an average molecular weight of at least about 400,000 Daltons;

the high molecular weight hydrophilic polymer is chosen from polyethylene oxide, xanthan gum, hydroxypropyl cellulose, hydroxypropylmethyl cellulose and combinations thereof;

the high molecular weight hydrophilic polymer is present in an amount from about 2% to about 10% by weight of the pharmaceutical composition;

the effervescent system comprises a) an acid component chosen from an organic acid, an inorganic acid, and combinations thereof and b) a base component;

the acid component chosen from an alkali metal bicarbonate, an alkaline earth metal bicarbonate, an alkali metal carbonate, an organic carbonate, and combinations thereof;

the effervescent system is present in an amount from about 50% to about 70% by weight of the pharmaceutical composition; and

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

11. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a solid dosage form prepared by a process comprising:

a) forming a mixture comprising the at least one active pharmaceutical ingredient (API) or a pharmaceutically acceptable salt thereof, the at least one low molecular weight hydrophilic polymer, the at least one high molecular weight hydrophilic polymer, and the effervescent system;

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

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

13. The process of claim 11, further comprising coating the solid dosage form with a coating.

14. The process of claim 11, wherein the low molecular weight hydrophilic polymer has an average molecular weight of no more than about 200,000 Daltons;

the low molecular weight hydrophilic polymer is chosen from a polyalkylene oxide, a cellulose ether, a polyalkylene glycol, a Poloxamer, and combinations thereof; and

the low molecular weight hydrophilic polymer is present in an amount from about 5% to about 50% by weight of the solid dosage form.

15. The process of claim 11, wherein the high molecular weight hydrophilic polymer has an average molecular weight of at least about 400,000 Daltons;

the high molecular weight hydrophilic polymer is chosen from a polyalkylene oxide, a cellulose ether, a polysaccharide, and combinations thereof; and

the high molecular weight hydrophilic polymer is present in an amount from about 0.1% to about 30% by weight of the solid dosage form.

16. The process of claim 11, 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 the effervescent system is present in an amount from about 20% to about 90% by weight of the solid dosage form.

17. The process of claim 11, wherein the mixture formed in step (a) further comprises a lubricant that is present in an amount from about 0.1% to about 2% by weight of the solid dosage form.

18. The process of claim 11, 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 11, wherein the heating step (c) occurs at a temperature of less than about 90°

C.

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

a) forming a mixture comprising at least one low molecular weight hydrophilic polymer, at least one high molecular weight hydrophilic polymer, and 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.