Immediate release, abuse deterrent pharmaceutical compositions
View Patent ↗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.
1. A pharmaceutical composition comprising at least one active pharmaceutical ingredient (API) or a pharmaceutically acceptable salt thereof, about 15% to about 35% by weight of at least one low molecular weight hydrophilic polymer, about 1% to about 15% by weight of at least one high molecular weight hydrophilic polymer, and about 50% to about 70% by weight of an effervescent system, wherein the at least one low molecular weight hydrophilic polymer has an average molecular weight of no more than 200,000 Daltons, the at least one high molecular weight hydrophilic polymer has an average molecular weight of at least 400,000 Daltons, the pharmaceutical composition is a solid dosage form that has been heated at a temperature from about 50° C. to about 80° C. to plasticize and/or cure at least one of the low or high molecular weight hydrophilic polymers, and the solid dosage form provides immediate release of the at least one API and deters abuse by breaking into a plurality of particles having an average diameter of greater than about 250 microns rather than a fine powder when crushed, ground, or pulverized.
2. The pharmaceutical composition of claim 1 , wherein the at least one low molecular weight hydrophilic polymer is chosen from a polyalkylene oxide, a cellulose ether, a polyalkylene glycol, a poloxamer, or combinations thereof.
3. The pharmaceutical composition of claim 1 , wherein the at least one high molecular weight hydrophilic polymer is chosen from a polyalkylene oxide, a cellulose ether, a polysaccharide, or combinations thereof.
4. The pharmaceutical composition of claim 1 , wherein the effervescent system comprises an a) acid component chosen from an organic acid, an inorganic acid, or 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, or combinations thereof.
5. The pharmaceutical composition of claim 1 , wherein the at least one 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, or morphine.
6. The pharmaceutical composition of claim 1 , which forms a viscous mixture or gel when in contact with a small volume of a suitable solvent.
7. The pharmaceutical composition of claim 1 , wherein the solid dosage form has a hardness of at least about 15 kiloponds.
8. The pharmaceutical composition of claim 1 , which releases at least about 80% of the at least one API within about 30 minutes when measured using an USP-approved in vitro release procedure.
9. The pharmaceutical composition of claim 1 , wherein the at least one low molecular weight hydrophilic polymer is chosen from polyethylene oxide, hydroxypropylmethyl cellulose, sodium carboxymethyl cellulose, polyethylene glycol, a poloxamer, or combinations thereof; the at least one high molecular weight hydrophilic polymer is chosen from polyethylene oxide, xanthan gum, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, or combinations thereof; the effervescent system comprises a) an acid component chosen from an organic acid, an inorganic acid, or 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, or combinations thereof; and the at least one API is an opioid chosen from oxycodone, oxymorphone, hydrocodone, hydromorphone, codeine, or morphine.
10. The pharmaceutical composition of claim 9 , wherein the at least one low molecular weight hydrophilic polymer comprises polyethylene oxide, hydroxypropylmethyl cellulose, and sodium carboxymethyl cellulose; and the at least one high molecular weight polymer comprises polyethylene oxide and xanthan gum.
11. The pharmaceutical composition of claim 10 , wherein the effervescent system comprise tartaric acid and sodium bicarbonate.
12. The pharmaceutical composition of claim 9 , wherein the solid dosage form has a hardness of at least about 20 kiloponds.
13. The pharmaceutical composition of claim 9 , which releases at least about 80% of the at least one API within about 30 minutes when measured using an USP-approved in vitro release procedure.
14. The pharmaceutical composition of claim 13 , which releases at least about 85% of the at least one API within about 30 minutes.
15. The pharmaceutical composition of claim 14 , which releases at least about 90% of the at least one API within about 30 minutes.
16. The pharmaceutical composition of claim 15 , which releases at least about 95% of the at least one API within about 30 minutes.
17. The pharmaceutical composition of claim 16 , which releases at least about 99% of the at least one API within about 30 minutes.
18. The pharmaceutical composition of claim 1 , wherein the solid dosage form is prepared by a process comprising:
a) forming a mixture comprising the at least one active pharmaceutical ingredient (API) or a pharmaceutically acceptable salt thereof, about 15% to about 35% by weight of the at least one low molecular weight hydrophilic polymer with an average molecular weight of no more than 200,000 Daltons, about 1% to about 15% by weight of the at least one high molecular weight hydrophilic polymer with an average molecular weight of at least 400,000 Daltons and about 50% to about 70% by weight of the effervescent system;
b) forming the mixture into a solid dosage unit; and
c) heating the solid dosage unit at a temperature from about 50° C. to about 80° C. to yield the solid dosage form.