Pharmaceutical compositions resistant to abuse
The present invention provides immediate release pharmaceutical compositions for oral administration that are resistant to abuse.
1. An abuse resistant oral pharmaceutical composition, comprising a shell resistant to physical tampering and a matrix composition,
wherein the matrix composition is at least partly contained within the shell and comprises an active drug substance and a polyethylene oxide polymer,
wherein the shell comprises an outer shell wall having an inner surface and an outer surface, the outer surface being a double curved surface, wherein the shell extends from a first end to a second end, the shell having a length in a range of from 4 mm to 20 mm, wherein the outer shell wall has a first opening at the first end and a second opening at the second end, the first opening and the second opening having an area in a range of from about 1 mm 2 to about 100 mm 2 and wherein the outer shell wall is of varying thickness and has a maximum thickness in a range of from 1.0 mm to about 10 mm, the outer shell wall being impermeable to water.
2. The composition of claim 1 , wherein the matrix composition comprises one or more polyethylene oxide polymers having a total average molecular weight of from 200,000 to 300,000.
3. The composition of claim 1 , wherein the matrix composition further comprises a plasticizer.
4. The composition of claim 1 , wherein the matrix composition further comprises a stabilizer.
5. The composition of claim 1 , wherein the matrix composition further comprises a gelling agent.
6. The composition of claim 1 , wherein the matrix composition further comprises an antioxidant.
7. The composition of claim 1 , wherein the shell comprises polylactic acid.
8. The composition of claim 7 , wherein the shell further comprises a polyethylene oxide polymer.
9. The composition of claim 1 , wherein the active drug substance is selected from morphine, oxycodone, hydrocodone, hydromorphone, oxymorphone, ketorolac, amphetamine, methylphenidate, diazepam, and pharmaceutically acceptable salts thereof.
10. The composition of claim 1 , wherein
the active drug substance comprises one or more of morphine and pharmaceutically acceptable salts thereof;
the matrix composition comprises one or more polyethylene oxide polymers having a total average molecular weight of from 200,000 to 300,000; butylated hydroxytoluene; optionally, a poloxamer; and optionally, mannitol; and
the shell comprises polylactic acid and, optionally, a polyethylene oxide polymer.
11. The composition of claim 10 , wherein the matrix composition further comprises a stabilizer.
12. The composition of claim 1 , wherein
the active drug substance comprises one or more of oxycodone and pharmaceutically acceptable salts thereof;
the matrix composition comprises one or more polyethylene oxide polymers having a total average molecular weight of from 200,000 to 300,000; butylated hydroxytoluene; optionally, a poloxamer; optionally, a methacrylic acid-methyl methacrylate (Eudragit®) copolymer; and, optionally, hydroxypropylmethylcellulose; and
the shell comprises polylactic acid and, optionally, a polyethylene oxide polymer.
13. The composition of claim 12 , wherein the matrix composition further comprises a stabilizer.
14. The composition of claim 1 , wherein
the active drug substance comprises one or more of hydrocodone and pharmaceutically acceptable salts thereof;
the matrix composition comprises one or more polyethylene oxide polymers having a total average molecular weight of from 200,000 to 300,000; butylated hydroxytoluene; optionally, a poloxamer; and, optionally, hydroxypropylmethylcellulose; and
the shell comprises polylactic acid and, optionally, a polyethylene oxide polymer.
15. The composition of claim 14 , wherein the matrix composition further comprises a stabilizer.
16. The composition of claim 1 , wherein
the active drug substance comprises one or more of hydromorphone and pharmaceutically acceptable salts thereof;
the matrix composition comprises one or more polyethylene oxide polymers having a total average molecular weight of from 200,000 to 300,000; butylated hydroxytoluene; optionally, a poloxamer; and, optionally, hydroxypropylmethylcellulose; and
the shell comprises polylactic acid and, optionally, a polyethylene oxide polymer.
17. The composition of claim 16 , wherein the matrix composition further comprises a stabilizer.
18. The composition of claim 1 , wherein
the active drug substance comprises one or more of oxymorphone and pharmaceutically acceptable salts thereof;
the matrix composition comprises one or more polyethylene oxide polymers having a total average molecular weight of from 200,000 to 300,000; butylated hydroxytoluene; optionally, a poloxamer; and, optionally, hydroxypropylmethylcellulose; and
the shell comprises polylactic acid and, optionally, a polyethylene oxide polymer.
19. The composition of claim 18 , wherein the matrix composition further comprises a stabilizer.
20. The composition of claim 1 , wherein
the active drug substance comprises one or more of ketorolac and pharmaceutically acceptable salts thereof;
the matrix composition comprises one or more polyethylene oxide polymers having a total average molecular weight of from 200,000 to 300,000; butylated hydroxytoluene; optionally, a poloxamer; and, optionally, hydroxypropylmethylcellulose; and
the shell comprises polylactic acid and, optionally, a polyethylene oxide polymer.
21. The composition of claim 20 , wherein the matrix composition further comprises a stabilizer.
22. The composition of claim 1 , wherein
the active drug substance comprises one or more of amphetamine and pharmaceutically acceptable salts thereof;
the matrix composition comprises one or more polyethylene oxide polymers having a total average molecular weight of from 200,000 to 300,000; butylated hydroxytoluene; optionally, a poloxamer; and, optionally, hydroxypropylmethylcellulose; and
the shell comprises polylactic acid and, optionally, a polyethylene oxide polymer.
23. The composition of claim 22 , wherein the matrix composition further comprises a stabilizer.
24. The composition of claim 1 , wherein
the active drug substance comprises one or more of methylphenidate and pharmaceutically acceptable salts thereof;
the matrix composition comprises one or more polyethylene oxide polymers having a total average molecular weight of from 200,000 to 300,000; butylated hydroxytoluene; optionally, a poloxamer; and, optionally, hydroxypropylmethylcellulose; and
the shell comprises polylactic acid and, optionally, a polyethylene oxide polymer.
25. The composition of claim 24 , wherein the matrix composition further comprises a stabilizer.
26. The composition of claim 1 , wherein
the active drug substance comprises one or more of diazepam and pharmaceutically acceptable salts thereof;
the matrix composition comprises one or more polyethylene oxide polymers having a total average molecular weight of from 200,000 to 300,000; butylated hydroxytoluene; optionally, a poloxamer; and, optionally, hydroxypropylmethylcellulose; and
the shell comprises polylactic acid and, optionally, a polyethylene oxide polymer.
27. The composition of claim 26 , wherein the matrix composition further comprises a stabilizer.