Claims for Patent: 9,750,703

Summary for Patent: 9,750,703

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)
Application Number:	15/045,975
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,750,703
Patent Claims:	1. A solid controlled release dosage form comprising: a core comprising a first portion of hydrocodone or a pharmaceutically acceptable salt thereof dispersed in a first matrix material; and a shell encasing the core and comprising a second portion of the hydrocodone or pharmaceutically acceptable salt thereof dispersed in a second matrix material; wherein the first matrix material, the second matrix material, or both the first and second matrix material comprises polyethylene oxide having an average molecular weight from about 300,000 to about 10,000,000, wherein the dosage form is cured at a temperature of at least 60 .degree. C. for at least 1 minute; wherein the amount of hydrocodone or pharmaceutically acceptable salt thereof released from the dosage form at 2 hours is less than about 25%, at 4 hours is from about 10% to about 30%, at 8 hours is from about 20% to about 60%, at 12 hours is from about 40% to about 90%, and at 18 hours is greater than about 70%; wherein the dosage form can be flattened without breaking, wherein the thickness of the dosage form after flattening corresponds to no more than about 20% of the thickness of the dosage form before flattening; and the amount of hydrocodone or pharmaceutically acceptable salt thereof released at 0.5 hour from a flattened dosage form deviates no more than about 20% points from a non-flattened dosage form 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 solid controlled release dosage form of claim 1, wherein the second matrix material comprises polyethylene oxide having an average molecular weight from about 1,000,000 to about 10,000,000 as measured by correlation to viscosity. 3. The solid controlled release dosage form of claim 1, wherein the first matrix material, the second matrix material, or both the first and second matrix materials comprise a cellulose ether. 4. The solid controlled release dosage form of claim 3, wherein the first matrix material, the second matrix material, or both the first and second matrix materials comprise a hydroxyalkylcellulose. 5. The solid controlled release dosage form of claim 4, wherein the hydroxyalkylcellulose is hydroxypropylcellulose. 6. The solid controlled release dosage form of claim 3, wherein the first matrix material, the second matrix material, or both the first and second matrix materials comprise microcrystalline cellulose. 7. The solid controlled release dosage form of claim 6, comprising a compressed dispersion of the first portion of hydrocodone or pharmaceutically acceptable salt thereof and the second matrix material. 8. The solid controlled release dosage form of claim 6, comprising granules comprising the first portion of hydrocodone or pharmaceutically acceptable salt thereof and the first matrix material. 9. The solid controlled release dosage form of claim 8, wherein the granules are compressed into a tablet. 10. The solid controlled release dosage form of claim 6, wherein the hydrocodone or pharmaceutically acceptable salt thereof is hydrocodone bitartrate. 11. The solid controlled release dosage form of claim 10, wherein the amount of hydrocodone bitartrate in the dosage form is from about 0.5 mg to about 1250mg. 12. The solid controlled release dosage form of claim 6, which provides a C.sub.24/C.sub.max ratio of hydrocodone of about 0.55 to about 1.0 after oral administration to a subject. 13. The solid controlled release dosage form of claim 6, which provides a T.sub.max (h) of hydrocodone from about 4 to about 20 hours after oral administration to a subject. 14. The solid controlled release dosage form of claim 12, wherein the administration is a first administration to a population of subjects. 15. The solid controlled release dosage form of claim 12, wherein the administration is steady state administration to a subject. 16. The solid controlled release dosage form of claim 6, which contains about 20 mg hydrocodone or pharmaceutically acceptable salt thereof. 17. The solid controlled release dosage form of claim 6, which contains about 120 mg hydrocodone or pharmaceutically acceptable salt thereof. 18. The solid controlled release dosage form of claim 6, which provides a mean AUC (ng*h/mL) after oral administration to a subject of about 250 to about 400 per each 20 mg hydrocodone or pharmaceutically acceptable salt thereof included in the dosage form. 19. The solid controlled release dosage form of claim 6, which provides a mean C.sub.max (ng/mL) after oral administration to a subject of about 10 to about 30 per each 20 mg hydrocodone or pharmaceutically acceptable salt thereof included in the dosage form. 20. The solid controlled release dosage form of claim 6, which provides a mean T.sub.max (h) after oral administration to a subject of about 10 to about 20. 21. The solid controlled release dosage form of claim 6, which provides a mean T.sub.1/2 (h) after oral administration to a subject of about 5 to about 10. 22. The solid controlled release dosage form of claim 6, which provides a mean T.sub.lag (h) after oral administration to a subject of about 0.01 to about 0.2. 23. The solid controlled release dosage form of claim 6, wherein the mean C.sub.24/C.sub.max ratio is about 0.2 to about 0.8 after oral administration to a subject. 24. The solid controlled release dosage form of claim 23, wherein the administration is in the fasted state. 25. The solid controlled release dosage form of claim 6, wherein the mean AUC (ng*h/mL) after oral administration to a subject in the fed state is less than 20% higher than the AUC (ng*h/mL) after oral administration to a subject in the fasted state. 26. The solid controlled release dosage form of claim 6, wherein the mean C.sub.max (ng/mL) after oral administration to a subject in the fed state is less than 80% higher than the C.sub.max after oral administration to a subject in the fasted state. 27. The solid controlled release dosage form of claim 6, wherein the mean T.sub.max (h) after oral administration to a subject in the fed state is within 25% of the T.sub.max (h) after oral administration to a subject in the fasted state. 28. The solid controlled release dosage form of claim 6, wherein the mean T.sub.1/2 (h) after oral administration to a subject in the fed state is within 8% of the T.sub.1/2 after oral administration to a subject in the fasted state. 29. The solid controlled release dosage form of claim 1, wherein the shell comprises a compression coating. 30. The solid controlled release dosage form of claim 29, wherein the shell further comprises a hydrophilic coating over the compression coating. 31. The solid controlled release dosage form of claim 30, wherein the hydrophilic coating is a cosmetic coat. 32. The solid controlled release dosage form of claim 1, wherein the first matrix material comprises polyethylene oxide having an average molecular weight from about 300,000to about 3,000,000 and the second matrix material comprises polyethylene oxide having an average molecular weight from about 4,000,000 to about 10,000,000, all as measured by correlation to viscosity. 33. The solid controlled release dosage form of claim 1, wherein the amount of hydrocodone or pharmaceutically acceptable salt thereof released from the dosage form is proportional within 20% at 8 and 24 hours, all 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. 34. A solid controlled release dosage form comprising: a core comprising a first portion of hydrocodone bitartrate dispersed in a first matrix material; and a layer encasing the core and comprising a second portion of hydrocodone bitartrate dispersed in a second matrix material; wherein the first matrix material, the second matrix material, or both the first and second matrix materials comprise polyethylene oxide having an average molecular weight from about 300,000 to about 10,000,000, wherein the dosage form is cured at a temperature of at least 60.degree. C. for at least 1 minute; wherein the amount of hydrocodone bitartrate released from the dosage form at 2 hours is less than about 25%, at 4 hours is from about 10% to about 30%, at 8 hours is from about 20% to about 60%, at 12 hours is from about 40% to about 90%, and at 18 hours is greater than about 70%; wherein the dosage form can be flattened without breaking, wherein the thickness of the dosage form after flattening corresponds to no more than about 20% of the thickness of the dosage form before flattening; and the amount of hydrocodone bitartrate released at 0.5 hour from a flattened dosage form deviates no more than about 20% points from a non-flattened dosage form 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. 35. The solid controlled release dosage form of claim 33, wherein the layer is a compression coating. 36. The solid controlled release dosage form of claim 35, further comprising a hydrophilic coating over the layer. 37. The solid controlled release dosage form of claim 35, wherein the hydrophilic coating is a cosmetic coat. 38. The solid controlled release dosage form of claim 33, wherein the first matrix material comprises polyethylene oxide having an average molecular weight from about 300,000to about 3,000,000 and the second matrix material comprises polyethylene oxide having an average molecular weight from about 4,000,000 to about 10,000,000, all as measured by correlation to viscosity. 39. The solid controlled release dosage form of claim 34, wherein the amount of hydrocodone bitartrate released from the dosage form is proportional within 20% at 8 and 24hours, all as measured by an in-vitro dissolution in a USP Apparatus 1 (basket) at 100 rpm in 900ml simulated gastric fluid without enzymes (SGF) at 37.degree. C.