Methylphenidate extended release chewable tablet

• US 11,103,495 B2
• Filed: 03/26/2021
• Issued: 08/31/2021
• Est. Priority Date: 08/15/2012
• Status: Active Grant

• Current Assignee: Tris Pharma Incorporated
• Original Assignee: Tris Pharma Incorporated
• Inventors: Tu, Yu-Hsing, Perumal, Ashok, Kathala, Kalyan
• Primary Examiner(s): Young, Micah Paul
• Application Number:
  US17/213,744
• Publication Number:
  US 20210213007A1
• Time in Patent Office: 158 Days
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 47/585 Ion exchange resins, e.g. polystyrene sulfonic acid resin
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/28 Dragees; Coated pills or tablets , e.g. with film or compression coating A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209
• CPC Class Codes: A61K 9/284 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates

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.

Claims

1. A racemic methylphenidate chewable tablet, wherein the chewable tablet is a uniform solid dispersion comprising:

(a) a water-insoluble, water-permeable, pH-independent barrier coated, racemic methylphenidate—

cation exchange resin complex in an optional matrix, wherein the barrier coating comprises a water-insoluble barrier coating polymer and a plasticizer, which barrier coating is present in an amount of about 10% w/w to about 70% w/w % based on the weight of the precoated racemic methylphenidate—

cation exchange resin complex—

optional matrix, wherein the barrier coating is over the precoated racemic methylphenidate—

cation exchange resin complex—

optional matrix and provides a sustained release profile to the racemic methylphenidate in (a), and wherein when present the matrix comprises the racemic methylphenidate—

cation exchange resin complex and further comprises a water-insoluble polymer or copolymer or a water-soluble polymer or copolymer; and

(b) at least one immediate release racemic methylphenidate component which releases racemic methylphenidate in (b) 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 (a);

wherein said chewable tablet is capable of being divided and providing tablet portions which retain the release profile for the racemic methylphenidate in the undivided tablet following oral dosing.

2. The extended release racemic methylphenidate tablet according to claim 1, wherein the water-insoluble, water-permeable, pH-independent barrier coated, racemic methylphenidate—

cation exchange resin complex—

optional matrix does not comprise a delayed release pH-dependent enteric coating.

3. The extended release racemic methylphenidate tablet according to claim 1, wherein the chewable tablet does not comprise a pH-dependent enteric coating.

4. The extended release racemic methylphenidate tablet according to claim 1, wherein the barrier coating is about 15% to about 65% by weight, of the precoated racemic methylphenidate—

cation exchange resin complex—

optional matrix.

5. The extended release racemic methylphenidate tablet according to claim 1, wherein the plasticizer is 2% w/w to about 50% w/w of the barrier coating.

6. The extended release racemic methylphenidate tablet according to claim 1, wherein the plasticizer is 2.5% w/w to about 20% w/w of the barrier coating.

7. The extended release racemic methylphenidate tablet according to claim 6, wherein the plasticizer comprises triacetin.

8. The extended release racemic methylphenidate tablet according to claim 1, wherein the optional matrix is absent.

9. The racemic methylphenidate chewable tablet according to claim 1, wherein the sustained release racemic methylphenidate of (a) provides about 60% w/w to about 80% w/w of the racemic methylphenidate, based on the total amount of racemic methylphenidate in the chewable tablet.

10. 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—

optional matrix.

11. The racemic methylphenidate chewable tablet according to claim 10, 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.

12. 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.

13. The racemic methylphenidate chewable tablet according claim 12, wherein the pharmaceutically acceptable salt is racemic methylphenidate HCl.

14. The racemic methylphenidate chewable tablet according to claim 8, 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.

15. 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%.

16. The racemic methylphenidate chewable tablet according to claim 1, wherein the water insoluble, water-permeable, pH-independent barrier coating comprises (a) a cured, water-permeable, non-ionic, pH-independent barrier coating comprising polyvinylacetate, a stabilizer, and a plasticizer, applied as an aqueous dispersion or (b) an ethylcellulose coating with a plasticizer.

17. 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.

18. The racemic methylphenidate chewable tablet according to claim 1, wherein the matrix is present and comprises polyvinylpyrolidone.

19. The chewable racemic methylphenidate tablet according to claim 1, wherein the matrix is present and comprises a water-insoluble polymer or co-polymer.

20. The racemic methylphenidate chewable tablet according to claim 1, wherein said tablet comprises the equivalent of 20 mg racemic methylphenidate HCl, the equivalent of 30 mg racemic methylphenidate HCl, or the equivalent of 40 mg racemic methylphenidate HCl.

29. A method for treating a patient having Attention Deficit Hyperactivity Disorder and/or Attention Deficit Disorder, said method comprising orally delivering the racemic methylphenidate chewable tablet according to claim 2 to the patient, wherein the racemic methylphenidate in the tablet provides a clinically observable psychological and/or behavioral response in the patient for a sustained period post-ingestion by the patient.

30. A method for treating a patient having Attention Deficit Hyperactivity Disorder and/or Attention Deficit Disorder, said method comprising orally delivering the racemic methylphenidate chewable tablet according to claim 1 to the patient, wherein the racemic methylphenidate of (a) provides sustained release of the racemic methylphenidate and the at least one immediate release racemic methylphenidate of (b) further provides release of racemic methylphenidate in less than 20 minutes.

21. A racemic methylphenidate chewable tablet, wherein the chewable tablet is a uniform solid dispersion comprising:

(a) a water-insoluble, water-permeable, pH-independent barrier coated, racemic methylphenidate—

cation exchange resin complex in an optional matrix, wherein the barrier coating comprises a water-insoluble barrier coating polymer and a plasticizer, which barrier coating is present in an amount of about 10% w/w to about 70% w/w % based on the weight of the precoated racemic methylphenidate—

cation exchange resin complex—

optional matrix, wherein the barrier coating is over the precoated racemic methylphenidate—

cation exchange resin complex—

optional matrix and provides a sustained release profile to the racemic methylphenidate in (a), and wherein when present the matrix comprises the racemic methylphenidate—

cation exchange resin complex and further comprises a water-insoluble polymer or copolymer or a water-soluble polymer or copolymer;

(b) a first immediate release component which comprises an immediate release uncoated racemic methylphenidate—

ion exchange resin complex, wherein about 5% w/w to about 20% w/w of the total racemic methylphenidate in the tablet is provided by (b); and

(c) a second immediate release racemic methylphenidate component which comprises an uncomplexed racemic methylphenidate, wherein about 5% w/w to about 20% w/w of the total racemic methylphenidate in the tablet is provided by (c);

wherein said chewable tablet is capable of being divided and providing tablet portions which retain the release profile for the racemic methylphenidate in the undivided tablet following oral dosing.

22. The racemic methylphenidate chewable tablet according to claim 21, wherein about 60% w/w to about 80% w/w of the racemic methylphenidate in the tablet is provided by (a).

23. The racemic methylphenidate chewable tablet according to claim 21, wherein the first immediate release component (b) is about 15% w/w of the total racemic methylphenidate in the tablet and/or the second immediate release component (c) is about 15% w/w of the total racemic methylphenidate in the tablet.

24. The extended release racemic methylphenidate tablet according to claim 21, wherein the chewable tablet does not comprise a pH-dependent enteric coating.

25. The extended release racemic methylphenidate tablet according to claim 21, wherein the barrier coating is about 15% to about 65% by weight, of the precoated racemic methylphenidate—

cation exchange resin complex—

optional matrix.

26. The extended release racemic methylphenidate tablet according to claim 21, wherein the plasticizer is 2% w/w to about 50% w/w of the barrier coating.

27. The extended release racemic methylphenidate tablet according to claim 21, wherein the plasticizer is 2.5% w/w to about 20% w/w of the barrier coating.

28. The extended release racemic methylphenidate tablet according to claim 21, wherein the optional matrix is absent.