Claims for Patent: 9,844,544

Summary for Patent: 9,844,544

Title:	Methylphenidate extended release chewable tablet
Abstract:	An oral methylphenidate extended release tablet is described, which can be scored and still retain its extended release profile. The tablet contains a combination of an uncoated methylphenidate-ion exchange resin complex, a barrier coated methylphenidate-ion exchange resin complex-matrix, and an uncomplexed methylphenidate active component. Following administration of a single dose of the extended release methylphenidate chewable tablet, a therapeutically effective amount of methylphenidate is reached in less than about 20 minutes and the composition provides a twelve-hour extended release profile.
Inventor(s):	Tu; Yu-Hsing (West Windsor, NJ), Perumal; Ashok (Monmouth Junction, NJ), Kathala; Kalyan (Monmouth Junction, NJ)
Assignee:	TRIS PHARMA, INC (Monmouth Junction, NJ)
Application Number:	15/009,480
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,844,544
Patent Claims:	1. A method for treating a patient with a disorder treatable by methylphenidate, said method comprising providing said patient with an effective amount of a methylphenidate extended release chewable tablet which is a uniform solid dispersion comprising: (a) a sustained release racemic methylphenidate component comprising a water-insoluble, water-permeable, pH-independent barrier coated, racemic methylphenidate--ion exchange resin complex in a polymeric matrix, wherein said barrier coating which provides a sustained release profile to the racemic methylphenidate is over the racemic methylphenidate--ion exchange resin complex-matrix; (b) a first immediate release component which comprises an immediate release uncoated racemic methylphenidate--ion exchange resin complex; (c) a second immediate release racemic methylphenidate component which comprises an uncomplexed racemic methylphenidate acceptable salt thereof; wherein said first immediate release component (b) has a slower onset of release than (c); wherein about 50% w/w to about 90% w/w of the racemic methylphenidate active component is provided by the sustained release component based on the total amount of racemic methylphenidate in the tablet, and wherein said chewable tablet is capable of being divided and providing tablet portions which retain a therapeutically effective extended release profile, and a pharmacokinetic profile in which the methylphenidate has at least one of: a geometric mean for area under the curve (AUC).sub.0-.infin. of about 110 ng-hr/mL to about 140 ng-hr/mL and a geometric mean C.sub.max of about 10 ng/mL to about 15 ng/mL, under fasted and fed conditions in adults following a single oral administration of a chewable tablet comprising the equivalent of 40 mg racemic methylphenidate HCl. 2. The method according to claim 1, wherein said patient has been diagnosed with attention deficit hyperactivity disorder, postural orthostatic tachycardia syndrome, or narcolepsy. 3. The method according to claim 1, wherein C.sub.max is about 12 ng/mL to about 13 ng/mL. 4. The method according to claim 1, wherein geometric mean AUC.sub.0-.infin. is about 113 ng-hr/mL to about 138 ng-hr/mL. 5. The method according to claim 1, the sustained release methylphenidate component provides about 60% w/w to about 80% w/w of the methylphenidate in the chewable tablet, based on the total amount of methylphenidate in the tablet. 6. The method according to claim 1, wherein the immediate release uncoated racemic methylphenidate-ion exchange resin complex (b) and immediate release uncomplexed racemic methylphenidate (c) together comprise 20% w/w to about 40% w/w of the total racemic methylphenidate in the chewable tablet. 7. The method according to claim 1, wherein the ratio of the immediate release uncoated methylphenidate--ion exchange resin complex (b) to immediate release component uncomplexed methylphenidate (c) is in the range of about 3:1 based on the total weight of immediate release components. 8. The method according to claim 1, wherein the immediate release racemic methylphenidate--ion exchange resin complex is about 5% w/w to about 35% w/w of the total racemic methylphenidate in the chewable tablet. 9. The method according to claim 1, wherein the immediate release uncomplexed racemic methylphenidate (c) is in the form of a pharmaceutically acceptable salt. 10. The method according to claim 9, wherein the immediate release uncomplexed racemic methylphenidate (c) is in the form of racemic methylphenidate HCl. 11. The method according to claim 1, wherein the immediate release uncomplexed racemic methylphenidate (c) is about 5% w/w to about 35% w/w of the total racemic methylphenidate in the chewable tablet, based on a calculation of total racemic methylphenidate in the tablet. 12. The method according to claim 1, wherein the tablet comprises immediate release methylphenidate--ion exchange resin complex of (b) is about 15% w/w of the racemic methylphenidate in the tablet and a faster onset immediate release uncomplexed racemic methylphenidate (c) in about 15% w/w, based on a calculation of total racemic methylphenidate in the tablet. 13. The method according to claim 1, wherein the tablet has a hardness in the range of about 8 kp to about 23 kp. 14. The method according to claim 1, wherein the water insoluble, water-permeable, pH-independent barrier coating has an elongation factor range of about 150% to about 400% and is selected from (a) a cured, water-permeable, non-ionic, pH-independent barrier coating comprising polyvinylacetate, a stabilizer, and a plasticizer, applied as an aqueous dispersion; (b) an ionic, pH-independent, acrylic based coating comprising a polymer or copolymer comprising ethyl acrylate and methyl methacrylate applied as an aqueous dispersion; and (c) a solvent-based ethylcellulose coating, optionally with a plasticizer. 15. The method according to claim 14, wherein the barrier coating over the methylphenidate-ion exchange resin complex-matrix of (a) is a cured, water-insoluble, water-permeable, non-ionic, pH-independent barrier coating comprises about 70 to about 90% w/w polyvinylacetate, a stabilizer, and about 2 to about 10% w/w of a plasticizer. 16. The method according to claim 15, wherein the barrier coating layer is about 25% to about 35%, by weight, of the coated racemic methylphenidate--ion exchange resin complex-matrix. 17. The method according to claim 1, wherein the polymeric matrix comprises polyvinylpyrolidone. 18. The method according to claim 1, wherein the polymeric matrix further comprises a water-insoluble polymer. 19. The method according to claim 16, wherein the barrier coating over the methylphenidate--ion exchange resin complex-matrix of (a) has a pH-independent, acrylic based coating, which said coating comprises a blend of (i) a poly(ethyl acrylate-co-methyl methacrylate-co-trimethylammonioethyl methacrylate chloride) in a ratio of 1:2:0.1 and (ii) poly(ethyl acrylate-co-methyl methacrylate-co-trimethylammonioethyl methacrylate chloride) in a ratio of 1:2:0.2. 20. The method according to claim 1, wherein the chewable tablet further comprises a non-functional outer top coating layer. 21. The method according to claim 1, wherein the chewable tablet further comprises one or more excipients. 22. The method according to claim 1, wherein the chewable tablet has a pharmacokinetic profile for racemic methylphenidate comprising a single mean plasma concentration peak. 23. The method according to claim 22, wherein the single mean plasma concentration peak is between about 4 hours to about 5.25 hours under fasted and fed conditions. 24. The method according to claim 1, wherein said tablet comprises the equivalent of 40 mg racemic methylphenidate HCl. 25. The method according to claim 1, wherein said tablet comprises the equivalent of 30 mg racemic methylphenidate HCl. 26. The method according to claim 1, wherein said tablet comprises the equivalent of 20 mg racemic methylphenidate HCl. 27. The method according to claim 1, wherein said tablet is scored. 28. An extended release racemic methylphenidate chewable tablet, wherein said chewable tablet is a uniform solid dispersion comprising: (a) a sustained release, racemic methylphenidate component comprising a water-insoluble, water-permeable, pH-independent barrier coated, racemic methylphenidate-cation exchange resin complex which comprises: (i) a racemic methylphenidate-cation exchange resin complex comprising racemic methylphenidate and a pharmaceutically acceptable cation ion exchange resin, wherein the racemic methylphenidate is bound to the pharmaceutically acceptable cation exchange resin; (ii) a barrier coating over (i), wherein the barrier coating comprises a water-insoluble, water-permeable, pH-independent polymer and a plasticizer and the barrier coating is present in an amount of about 20% w/w to about 50% w/w % based on the weight of the racemic methylphenidate-cation exchange resin complex of (i) and provides a sustained release profile to the racemic methylphenidate; and wherein about 50% w/w to about 90% w/w of the racemic methylphenidate is provided by the sustained release component based on the total amount of racemic methylphenidate in the tablet; and (b) at least one immediate release racemic methylphenidate component which provides a release of the racemic methylphenidate in less than about 30 minutes as determined in an in vitro dissolution assay; wherein said chewable tablet is capable of being divided and providing tablet portions which retain a therapeutically effective extended release profile, and a pharmacokinetic profile in which the methylphenidate has at least one of: a geometric mean for area under the curve (AUC).sub.0-.infin. of about 110 ng-hr/mL to about 140 ng-hr/mL or a geometric mean C.sub.max of about 10 ng/mL to about 15 ng/mL, under fasted conditions in adults following a single oral administration of a chewable tablet which comprises the equivalent of 40 mg racemic methylphenidate HCl. 29. The extended release racemic methylphenidate chewable tablet according to claim 28, wherein the plasticizer is selected from propylene glycol, polyethylene glycol, dibutyl sebacate, propylene glycol, polyethylene glycol, polyvinyl alcohol, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, tributyl citrate, triacetin, 2-pyrrolidone, or mixtures thereof. 30. The extended release racemic methylphenidate chewable tablet according to claim 28, wherein the plasticizer comprises triethyl citrate. 31. The extended release racemic methylphenidate chewable tablet according to claim 28, wherein the water-insoluble, water-permeable, pH-independent polymer is present in an amount of about 70% to about 90% w/w, based on the weight of the final barrier coating layer. 32. The extended release racemic methylphenidate chewable tablet according to claim 28, wherein the immediate release methylphenidate component (b) is uncoated racemic methylphenidate-cation exchange resin complex which comprises racemic methylphenidate bound to a pharmaceutically acceptable cation exchange resin. 33. The extended release racemic methylphenidate chewable tablet according to claim 32, wherein the immediate release component (b) comprises about 20% w/w to about 40% w/w of the total racemic methylphenidate in the chewable tablet. 34. The extended release racemic methylphenidate chewable tablet according to claim 28, wherein the sustained release methylphenidate component provides about 60% w/w to about 80% w/w of the methylphenidate in the chewable tablet, based on the total amount of methylphenidate in the chewable tablet. 35. The extended release racemic methylphenidate chewable tablet according to claim 28, wherein the tablet has a hardness in the range of about 8 kp to about 23 kp. 36. The tablet according to claim 28, wherein the in vitro dissolution assay is performed placing the tablet in 900 mL 0.4 M potassium phosphate buffer with 37.degree. C..+-.5.degree. C. with a USP paddle speed of 75 rpm. 37. The tablet according to claim 28, wherein the tablet has a pharmacokinetic profile for racemic methylphenidate which comprises a single mean concentration peak. 38. The extended release racemic methylphenidate chewable tablet according to claim 28, wherein the barrier coat has an elongation factor of at least 150% to about 400% as measured by a texture analyzer. 39. The extended release racemic methylphenidate chewable tablet according to claim 38, wherein the barrier coat is selected from: (a) a cured, water-permeable, non-ionic, pH-independent barrier coating comprising polyvinylacetate, a stabilizer, and the plasticizer; (b) a pH-independent, acrylic based coating comprising a polymer or copolymer comprising ethyl acrylate and methyl methacrylate and a plasticizer; or (c) a water-permeable, non-ionic, pH-independent barrier coating comprising ethylcellulose and the plasticizer. 40. The extended release racemic methylphenidate chewable tablet according to claim 28, wherein the plasticizer is about 2.5% to about 20% by weight of the coating.