Claims for Patent: 10,857,143

Summary for Patent: 10,857,143

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:	16/700,517
Patent Claims:	1. A racemic methylphenidate chewable tablet comprising: a sustained release racemic methylphenidate component comprising a water-insoluble, water-permeable, pH-independent barrier coated, racemic methylphenidate-cation exchange resin complex in an optional polymeric matrix, wherein the barrier coating is present in an amount of about 20% w/w to about 50% w/w % based on the weight of the coated racemic methylphenidate-cation exchange resin complex-optional matrix, wherein the barrier coating provides a sustained release profile to the racemic methylphenidate and is over the racemic methylphenidate-cation exchange resin complex-optional matrix, and wherein when present the polymeric matrix comprises the racemic methylphenidate-cation exchange resin complex and a water-insoluble polymer or copolymer or a water-soluble polymer or copolymer; and at least one immediate release racemic methylphenidate component which provides a release of the racemic methylphenidate in the at least one immediate release component in less than about 30 minutes as determined in an in vitro dissolution assay; wherein about 50% w/w to about 90% w/w of the racemic methylphenidate in the tablet is provided by the sustained release racemic methylphenidate component based on the total amount of racemic methylphenidate in the chewable tablet. 2. The racemic methylphenidate chewable tablet according to claim 1, wherein at least one immediate release methylphenidate component releases in about 10 minutes. 3. The racemic methylphenidate chewable tablet according to claim 1, the sustained release racemic methylphenidate component provides about 60% w/w to about 80% w/w of the racemic methylphenidate in the chewable tablet, based on the total amount of racemic methylphenidate in the tablet. 4. The racemic methylphenidate chewable tablet according to claim 1, wherein the at least one immediate release component is a racemic methylphenidate-cation exchange resin complex. 5. The racemic methylphenidate chewable tablet according to claim 4, wherein the immediate release racemic methylphenidate-cation exchange resin complex comprises about 20% w/w to about 40% w/w of the total racemic methylphenidate in the chewable tablet. 6. The racemic methylphenidate chewable tablet according to claim 1, wherein the at least one immediate release component comprises uncomplexed racemic methylphenidate or a pharmaceutically acceptable salt thereof. 7. The racemic methylphenidate chewable tablet according claim 6, wherein the racemic methylphenidate salt is racemic methylphenidate HCl. 8. The racemic methylphenidate chewable tablet according to claim 6, wherein the composition comprises immediate release uncomplexed racemic methylphenidate or pharmaceutically acceptable salt in an amount of about 5% w/w to about 35% w/w of the total racemic methylphenidate in the chewable tablet. 9. The racemic methylphenidate chewable tablet according to claim 1, wherein the tablet has a hardness in the range of about 8 kp to about 23 kp. 10. The racemic methylphenidate chewable tablet according to claim 1, wherein the water insoluble, water-permeable, pH-independent barrier coating has a tensile strength in a 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) a 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. 11. The racemic methylphenidate chewable tablet according to claim 1, wherein the barrier coating over the racemic methylphenidate-cation exchange resin complex-optional 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. 12. The racemic methylphenidate chewable tablet according to claim 11, wherein the barrier coating layer is about 25% to about 35%, by weight, of the coated racemic methylphenidate-cation exchange resin complex-optional matrix. 13. The racemic methylphenidate chewable tablet according to claim 1, wherein the polymeric matrix is present and comprises polyvinylpyrolidone. 14. The chewable racemic methylphenidate tablet according to claim 1, wherein the polymeric matrix is present and comprises a water-insoluble polymer. 15. The racemic methylphenidate chewable tablet according to claim 14, wherein the barrier coating over the racemic methylphenidate-cation exchange resin complex-optional matrix of (a) has a pH-independent, acrylic based coating, which 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. 16. The racemic methylphenidate chewable according to claim 1, wherein pharmacokinetic profile further comprises the 90% confidence intervals of the geometric test/reference ratios of one or more of AUC0-3 or AUC0-4 of FIG. 1. 17. The racemic methylphenidate chewable tablet according to claim 1, wherein the methylphenidate plasma concentration, as determined under fasted and fed conditions following a single oral administration of said chewable tablet at a dose equivalent to 40 mg racemic methylphenidate HCl in adults, is equivalent to the plasma concentration curve of FIG. 1 from about 0 to about 8 hours. 18. The racemic methylphenidate chewable tablet according to claim 1, wherein the chewable tablet provides a therapeutically effective amount of methylphenidate in under about 1 hour and through about 8 hours following oral ingestion by a patient having attention deficit hyperactivity disorder. 19. The racemic methylphenidate chewable tablet according to claim 1, wherein said tablet comprises the equivalent of 40 mg racemic methylphenidate HCl. 20. The racemic methylphenidate chewable tablet according to claim 1, wherein said tablet comprises the equivalent of 20 mg racemic methylphenidate HCl. 21. The racemic methylphenidate chewable tablet according to claim 1, wherein said tablet comprises the equivalent of 30 mg racemic methylphenidate HCl. 22. A method for treating a subject having Attention Deficit Hyperactivity Disorder and/or Attention Deficit Disorder with racemic methylphenidate, said method comprising orally administering to said subject a racemic methylphenidate chewable tablet according to claim 1. 23. The method to claim 22, wherein the racemic methylphenidate chewable tablet provides a pharmacokinetic profile for methylphenidate which comprises the 90% confidence intervals of the geometric test/reference ratios of one or more of AUC0-3 or AUC0-4 of FIG. 1. 24. The method according to claim 22, wherein the racemic methylphenidate chewable tablet provides a methylphenidate plasma concentration, as determined under fasted and fed conditions following a single oral administration of said chewable tablet at a dose equivalent to 40 mg racemic methylphenidate HCl in adults, is equivalent to the plasma concentration curve of FIG. 1 from about 0 to about 8 hours. 25. The method according to claim 22, wherein said tablet comprises the equivalent of 40 mg racemic methylphenidate HCl. 26. The method according to claim 22, wherein said tablet comprises the equivalent of 20 mg racemic methylphenidate HCl. 27. The method according to claim 22, wherein said tablet comprises the equivalent of 30 mg racemic methylphenidate HCl.