Extended release, abuse deterrent dosage forms
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 at least one active pharmaceutical ingredient (API) or a pharmaceutically acceptable salt thereof, at least one polyvinyl ester, at least one poly-N-vinylamide, at least one plasticizer, at least one optional lubricant, at least one optional polyalkylene oxide, and at least one optional wetting agent.
2. The extended release, abuse deterrent dosage form of claim 1 , wherein the at least one API is oxycodone, oxymorphone, hydrocodone, hydromorphone, codeine, or morphine.
3. The extended release, abuse deterrent dosage form of claim 1 , wherein the at least one polyvinyl ester is polyvinyl acetate.
4. The extended release, abuse deterrent dosage form of claim 1 , wherein the at least one poly-N-vinylamide is polyvinylpyrrolidone.
5. The extended release, abuse deterrent dosage form of claim 1 , wherein the at least one plasticizer is polyethylene glycol, propylene glycol, glycerin, polyethylene glycol monomethyl ether, sorbitol sorbitan solution, triethyl cellulose, dicarboxylic acid ester, acetyl tributyl citrate, acetyl triethyl citrate, castor oil, vegetable oil, diacetylated monoglyceride, dibutyl sebacate, diethyl phthalate, triacetin, tributyrin, tributyl citrate, triethyl citrate, polaxamer, or combination thereof.
6. The extended release, abuse deterrent dosage form of claim 1 , wherein the at least one optional lubricant is magnesium stearate, calcium stearate, zinc stearate, colloidal silicon dioxide, hydrogenated vegetable oil, sterotex, polyoxyethylene monostearate, polyethylene glycol, sodium stearyl fumarate, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, light mineral oil, or combination thereof.
7. The extended release, abuse deterrent dosage form of claim 1 , wherein the at least one optional polyalkyene oxide is polyethylene oxide having an average molecular weight distribution from about 100,000 to about 7,000,000.
8. The extended release, abuse deterrent dosage form of claim 1 , wherein the at least one optional wetting agent is polyoxyethylene glycol alkyl ether, polyoxyethylene glycol sorbitan alkyl ester, polyethylene glycol ester, sorbitan fatty acid ester, glyceryl fatty acid esters, polyethylene glycol, block co-polymer of polyethylene glycol and polypropylene glycol, polaxamer, polyoxyethylene fatty acid amide, polysorbate, ethoxylated aliphatic alcohol, alkylphenol, alkyl sulfate, alkyl sulfonate, alkyl benzene sulfonate, alpha sulfonyl fatty acid, alkyl phosphate, dioctyl sulfosuccinate, isethionate, alkyl ether sulfate, methyl sarcosine, alkyltrimethylammonium bromide, cetyltrimethylammonium bromide, benzalkonium chloride; benzethonium chloride, (3-((3-cholamidopropyl) dimethylammonio)-1-propanesulfonate (CHAPS), lecithin, cocoaminopropyl betaine, or combination thereof.
9. The extended release, abuse deterrent dosage form of claim 1 , wherein the plurality of particles has an average particle size distribution from about 100 micrometers to about 1000 micrometers.
10. 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.
11. 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.
12. The extended release, abuse deterrent dosage form of claim 1 , wherein the dosage form is formulated for oral delivery.
13. The extended release, abuse deterrent dosage form of claim 12 , wherein the dosage form is a tablet.
14. The extended release, abuse deterrent dosage form of claim 13 , wherein the at least one pharmaceutically acceptable excipient is a binder, a filler, a super-disintegrant, a lubricant, an ion exchange resin powder, or a combination thereof.
15. The extended release, abuse deterrent dosage form of claim 13 , wherein the tablet further comprises an aversive agent chosen from an irritant, a bittering agent, an emetic, a dye, or a combination thereof.
16. The extended release, abuse deterrent dosage form of claim 12 , wherein the dosage form is a capsule.
17. The extended release, abuse deterrent dosage form of claim 16 , wherein the at least one pharmaceutically acceptable excipient is a gelling polymer, a filler, an effervescent system, a glidant, an ion exchange resin powder, or a combination thereof.
18. The extended release, abuse deterrent dosage form of claim 16 , wherein the capsule further comprises an aversive agent chosen from an irritant, a bittering agent, an emetic, a dye, or a combination thereof.
19. The extended release, abuse deterrent dosage form of claim 1 , wherein the at least one polyvinyl ester is polyvinyl acetate; the at least one poly-N-vinylamide is polyvinylpyrrolidone; the at least one plasticizer is diethyl phthalate or a combination of diethyl phthalate and polyethylene glycol; the at least one optional polyalkylene oxide is polyethylene oxide; the at least one optional lubricant is present and is magnesium stearate, silicon dioxide, or a combination thereof; and the at least one optional wetting agent is present and is sodium lauryl sulfate.
20. The extended release, abuse deterrent dosage form of claim 19 , wherein the at least one API is oxycodone, oxymorphone, hydrocodone, hydromorphone, codeine, or morphine.