Extended release, abuse deterrent dosage forms
View Patent ↗Extended release, abuse deterrent dosage forms comprising crush-resistant controlled-release particles that provide abuse deterrent properties to the dosage forms. The crush-resistant controlled-release particles, which comprise plastic/elastic polymers and at least one active pharmaceutical ingredient (API) or a pharmaceutically acceptable salt thereof, are prepared by a hot melt extrusion process.
1. An extended release, abuse deterrent dosage form comprising a plurality of particles and at least one pharmaceutically acceptable excipient, wherein the plurality of particles consists of a blend of polyvinyl acetate and polyvinylpyrrolidone, an optional polyethylene oxide, at least one plasticizer, a lubricant, an optional wetting agent, and an active pharmaceutical ingredient (API) chosen from oxycodone, oxymorphone, hydrocodone, hydromorphone, codeine, morphine, or a pharmaceutically acceptable salt thereof.
2. The extended release, abuse deterrent dosage form of claim 1 , wherein the at least one plasticizer is chosen from polyethylene glycol, diethyl phthalate, dibutyl sebecate, triacetin, glycerol, triethyl cellulose, castor oil, a polaxamer, or a combination thereof.
3. The extended release, abuse deterrent dosage form of claim 1 , wherein the lubricant is chosen from magnesium stearate, calcium stearate, zinc stearate, colloidal silicon dioxide, hydrogenated vegetable oils, sterotex, polyoxyethylene monostearate, polyethylene glycol, sodium stearyl fumarate, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, light mineral oil, or a combination thereof; and the optional wetting agent is chosen from a sorbitan fatty acid ester, a polyoxyethylene glycol alkyl ether, a polyoxyethylene glycol sorbitan alkyl ester, an alkyl sulfate, or a combination thereof.
4. The extended release, abuse deterrent dosage form of claim 1 , wherein the API is oxycodone or a pharmaceutically acceptable salt thereof.
5. The extended release, abuse deterrent dosage form of claim 1 , wherein the plurality of particles has an average particle size distribution from about 50 micrometers to about 1500 micrometers.
6. The extended release, abuse deterrent dosage form of claim 1 , wherein the plurality of particles is resistant to crushing, grinding, milling, or pulverizing to form a powder comprising particles having an average diameter of less than about 10 micrometers.
7. The extended release, abuse deterrent dosage form of claim 1 , wherein the plurality of particles has an increased particle size after grinding or milling for more than about 3 minutes.
8. The extended release, abuse deterrent dosage form of claim 1 , wherein the plurality of particles releases the API over an extended period of time when measured using an USP-approved in vitro release procedure.
9. The extended release, abuse deterrent dosage form of claim 1 , wherein the plurality of particles releases the API over an extended period of time when the dosage form is crushed, broken, ground, milled, or pulverized.
10. The extended release, abuse deterrent dosage form of claim 1 , wherein the dosage form is formulated for oral delivery.
11. The extended release, abuse deterrent dosage form of claim 10 , wherein the dosage form is a tablet chosen from a fast disintegrating/dissolving tablet, an orally disintegrating/dissolving tablet, or a conventional tablet.
12. The extended release, abuse deterrent dosage form of claim 11 , wherein the at least one pharmaceutically acceptable excipient is chosen from a binder, a filler, a super-disintegrant, a lubricant, an ion exchange resin powder, or a combination thereof.
13. The extended release, abuse deterrent dosage form of claim 11 , wherein the tablet further comprises an aversive agent chosen from an irritant, a bittering agent, an emetic, a dye, or a combination thereof.
14. The extended release, abuse deterrent dosage form of claim 10 , wherein the dosage form is a capsule.
15. The extended release, abuse deterrent dosage form of claim 14 , wherein the at least one pharmaceutically acceptable excipient is chosen from a gelling polymer, a filler, an effervescent system, a glidant, an ion exchange resin powder, or a combination thereof.
16. The extended release, abuse deterrent dosage form of claim 14 , wherein the capsule further comprises an aversive agent chosen from an irritant, a bittering agent, an emetic, a dye, or a combination thereof.
17. The extended release, abuse deterrent dosage form of claim 1 , wherein the plurality of particles is prepared by a process comprising blending the blend of polyvinyl acetate and polyvinylpyrrolidone, the optional polyethylene oxide, if present, the at least one plasticizer, the lubricant, the optional wetting agent, if present, and the API to form a blend; hot melt extruding the blend to form an extrudate; and pelletizing and milling the extrudate to form the plurality of particles.