Details for Patent: 9,744,136

Title:	Encased tamper resistant controlled release dosage forms
Abstract:	In certain embodiments, the present invention is directed to a solid controlled release dosage form comprising: a core comprising a first portion of an opioid analgesic dispersed in a first matrix material; and a shell encasing the core and comprising a second portion of the opioid analgesic dispersed in a second matrix material; wherein the amount of opioid analgesic released from the dosage form is proportional within 20% to elapsed time from 8 to 24 hours, as measured by an in-vitro dissolution in a USP Apparatus 1 (basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37 C.
Inventor(s):	Huang; Haiyong Hugh (Princeton, NJ)
Assignee:	Purdue Pharma L.P. (Stamford, CT)
Filing Date:	Sep 11, 2013
Application Number:	14/024,360
Claims:	1. A method of preparing a solid controlled release dosage form comprising: preparing a core comprising a first portion of an opioid analgesic dispersed in a first controlled release matrix material; and encasing the core in a shell comprising a second portion of the opioid analgesic dispersed in a second controlled release matrix material over the core; wherein the amount of opioid analgesic released from the dosage form at 2 hours is less than about 25%, the amount of opioid analgesic released from the dosage form at 4 hours is from about 10% to about 30%, the amount of opioid analgesic released from the dosage form at 8 hours is from about 20% to about 60%, the amount of opioid analgesic released from the dosage form at 12 hours is from about 40% to about 90%, the amount of opioid analgesic released from the dosage form at 18 hours is greater than about 70%; and wherein the amount of opioid analgesic released from the dosage form is proportional within 20% at 9 and 24 hours, as measured by an in-vitro dissolution in a USP Apparatus 1 (basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37.degree. C. 2. The method of preparing a solid controlled release dosage form of claim 1, wherein both the first controlled release matrix material and the second controlled release matrix material comprise polyethylene oxide. 3. The method of preparing a solid controlled release dosage form of claim 2, wherein the polyethylene oxide in the second controlled release matrix material has a higher viscosity than the polyethylene oxide in the first controlled release matrix material. 4. The method of preparing a solid controlled release dosage form of claim 2, wherein the first controlled release matrix material comprises polyethylene oxide having an average molecular weight from about 300,000 to about 10,000,000. 5. The method of preparing a solid controlled release dosage form of claim 4, wherein the second controlled release matrix material comprises polyethylene oxide having an average molecular weight from about 1,000,000 to about 10,000,000. 6. The method of preparing a solid controlled release dosage form of claim 5, wherein the weight ratio of the core to the shell is from about 1:0.5 to about 1:5. 7. The method of preparing a solid controlled release dosage form of claim 2, wherein the weight ratio of the first portion of opioid analgesic to polyethylene oxide in the first controlled release matrix material is from about 1:0.5 to about 1:100. 8. The method of preparing a solid controlled release dosage form of claim 1, wherein the ratio of opioid analgesic in the core to the opioid analgesic in the shell is from about 1:11 to about 10:1. 9. The method of preparing a solid controlled release dosage form of claim 1, wherein the opioid analgesic is hydrocodone bitartrate. 10. The method of preparing a solid controlled release dosage form of claim 9, wherein the total amount of hydrocodone bitartrate in the dosage form is from about 0.5 mg to about 1250 mg. 11. The method of preparing a solid controlled release dosage form of claim 2, wherein the dosage form is cured at a temperature of at least the softening point of the polyethylene oxide for at least 1 minute. 12. The method of preparing a solid controlled release dosage form of claim 11, wherein the dosage form is cured at a temperature of at least about 60.degree. C. 13. The method of preparing a solid controlled release dosage form of claim 1, that provides a C.sub.24/C.sub.max ratio of hydrocodone of about 0.55 to about 1.0 after administration. 14. The method of preparing a solid controlled release dosage form of claim 1, that provides a T.sub.max (h) of hydrocodone from about 4 to about 20 hours after administration. 15. A method of preparing a solid controlled release dosage form comprising: preparing a core comprising a first portion of an opioid analgesic dispersed in a first controlled release matrix material; and encasing the core in a shell comprising a second portion of the opioid analgesic dispersed in a second controlled release matrix material over the core; wherein both the first controlled release matrix material and the second controlled release matrix material comprise polyethylene oxide; wherein the amount of opioid analgesic released from the dosage form at 2 hours is less than about 25%, the amount of opioid analgesic released from the dosage form at 4 hours is from about 10% to about 30%, the amount of opioid analgesic released from the dosage form at 8 hours is from about 20% to about 60%, the amount of opioid analgesic released from the dosage form at 12 hours is from about 40% to about 90%, the amount of opioid analgesic released from the dosage form at 18 hours is greater than about 70%; and wherein the amount of opioid analgesic released from the dosage form is proportional within 20% at 8 and 24 hours, as measured by an in-vitro dissolution in a USP Apparatus 1 (basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37.degree. C. 16. The method of preparing a solid controlled release dosage form of claim 15, wherein the polyethylene oxide in the second controlled release matrix material has a higher viscosity than the polyethylene oxide in the first controlled release matrix material. 17. The method of preparing a solid controlled release dosage form of claim 15, wherein the first controlled release matrix material comprises polyethylene oxide having an average molecular weight from about 300,000 to about 10,000,000. 18. The method of preparing a solid controlled release dosage form of claim 17, wherein the second controlled release matrix material comprises polyethylene oxide having an average molecular weight from about 1,000,000 to about 10,000,000. 19. The method of preparing a solid controlled release dosage form of claim 18, wherein the weight ratio of the core to the shell is from about 1:0.5 to about 1:5. 20. The method of preparing a solid controlled release dosage form of claim 18, wherein the weight ratio of the first portion of opioid analgesic to polyethylene oxide in the first controlled release matrix material is from about 1:0.5 to about 1:100. 21. The method of preparing a solid controlled release dosage form of claim 15, wherein the opioid analgesic in the first portion is the same as the opioid analgesic in the second portion. 22. The method of preparing a solid controlled release dosage form of claim 15, wherein the opioid analgesic in the first portion is different than the opioid analgesic in the second portion. 23. The method of preparing a solid controlled release dosage form of claim 15, wherein the ratio of opioid analgesic in the core to of opioid analgesic in the shell is from about 1:1 to about 10:1. 24. The method of preparing a solid controlled release dosage form of claim 15, wherein the opioid analgesic is hydrocodone bitartrate. 25. The method of preparing a solid controlled release dosage form of claim 24, wherein the total amount of hydrocodone bitartrate in the dosage form is from about 0.5 mg to about 1250 mg. 26. The method of preparing a solid controlled release dosage form of claim 15, wherein the dosage form is cured at a temperature of at least the softening point of the polyethylene oxide for at least 1 minute. 27. The method of preparing a solid controlled release dosage form of claim 26, wherein the dosage form is cured at a temperature of at least about 60.degree. C. 28. The method of preparing a solid controlled release dosage form of claim 24, that provides a C.sub.24/C.sub.max ratio of hydrocodone of about 0.55 to about 1.0 after administration. 29. The method of preparing a solid controlled release dosage form of claim 24, that provides a T.sub.max (h) of hydrocodone from about 4 to about 20 hours after administration.