Rapidly expanding composition for gastric retention and controlled release of therapeutic agents, and dosage forms including the composition

• US 7,674,480 B2
• Filed: 06/22/2001
• Issued: 03/09/2010
• Est. Priority Date: 06/23/2000
• Status: Expired due to Fees

• Current Assignee: Teva Pharmaceuticals USA, Inc. (Teva Pharmaceutical Industries Limited)
• Original Assignee: Teva Pharmaceutical Industries Limited
• Inventors: Dahan, Mazal, Lerner, E. Itzhak, Rosenberger, Vered, Fleshner-Barak, Moshe, Makov, Yisrael
• Primary Examiner(s): Fubara; Blessing M
• Application Number:
  US09/887,204
• Publication Number:
  US 20040234608A1
• Time in Patent Office: 3,182 Days
• Field of Search: 424/484, 424/486, 424/473, 424/468, 424/433, 424/490, 424/846, 424/488, 514/76, 514/283, 514/89
• US Class Current: 424/488
• CPC Class Codes: A61K 31/663 Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
• CPC Class Codes: A61K 9/0065 Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
• 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 9/205 Polysaccharides, e.g. alginate, gums; Cyclodextrin
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/2086 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 9/284 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/286 Polysaccharides, e.g. gums; Cyclodextrin
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system

Abstract

The present invention provides a pharmaceutical composition for use in a dosage form for oral administration to a patient. The composition expands upon contact with gastric fluid and promotes retention of the dosage form in the patient'"'"'s stomach for a prolonged period of time. The present invention further provides pharmaceutical dosage forms containing an active ingredient, and the pharmaceutical composition. The forms are adapted for immediate or controlled release of the active ingredient. The dosage forms may be used advantageously in the treatment of Parkinson'"'"'s disease with levodopa and hyperactivity and attention deficit disorder with methylphenidate.

Claims

1. A pharmaceutical dosage form for oral administration to a patient providing pulsed gastric release of methylphenidate comprising:

a) a gastric retention vehicle composition comprising about 10 wt-% to about 75 wt-% superdisintegrant, about 2 wt-% to about 12 wt-% tannic acid, and about 20 to about 70 wt-% of a hydrogel, whereby the gastric retention vehicle composition is a homogenous solid matrix and the percentages are calculated with respect to the matrix exclusive of other excipients and the methylphenidate,

b) a plurality of first particles containing methylphenidate that are dispersed in the matrix, wherein the methylphenidate is released from the first particles into the stomach upon contact with gastric fluid, and

c) a plurality of second particles containing methylphenidate that are dispersed in the matrix, wherein each of the second particles is coated with a coating that is impermeable to methylphenidate and dissolves in gastric fluid, and, after a sufficient amount of the coating is dissolved, the methylphenidate is released from the second particles into the stomach,

wherein, upon contact with gastric fluid the gastric retention vehicle composition expands to a sufficient degree such that the dosage form is retained in the stomach at least until methylphenidate is released from the second particles.

2. A pharmaceutical dosage form of claim 1 further comprising a plurality of third particles containing methylphenidate that are dispersed in the matrix, wherein each of the third particles is coated with a coating that is impermeable to the methylphenidate and dissolves in gastric fluid and the methylphenidate is released from the third particles into the stomach after the methylphenidate is released from the second particles.

3. The pharmaceutical dosage form of claim 2, wherein the methylphenidate is released from the third particles into the stomach about 3 to about 5 hours after the methylphenidate is released from the second particles.

4. A pharmaceutical dosage form of claim 1 wherein the first particles are coated with a coating that delays release of the methylphenidate from said first particles, with the proviso that the first particles and the second particles are not released at the same time.

5. The pharmaceutical dosage form of claim 1, wherein the methylphenidate is released from the second particles into the stomach about 3 to about 5 hours after administration.

6. A method of treating hyperactivity or attention deficit disorder comprising administering a therapeutically effective amount of methylphenidate in the pharmaceutical dosage form of claim 1 to a patient in need thereof.

7. The pharmaceutical dosage form of claim 1, wherein the coating comprises a film coating agent selected from the group consisting of water soluble resins, water insoluble resins, waxes, lipids, and enteric resins.

8. The pharmaceutical dosage form of claim 1, wherein the superdisintegrant is selected from the group consisting of cross-linked carboxymethylcellulose sodium, sodium starch glycolate, and cross-linked polyvinyl pyrollidone.

9. The pharmaceutical dosage form of claim 1, wherein the hydrogel is hydroxypropyl methyl cellulose or a mixture of hydroxypropyl methyl cellulose and hydroxypropyl cellulose or a cross-linked acrylate polymer.

10. The pharmaceutical dosage form of claim 1, comprising from about 10 wt. % to about 30 wt. % hydroxypropyl methylcellulose, from about 40 wt. % to about 60 wt. % hydroxypropyl cellulose, and about 4 wt. % to about 12 wt. % tannic acid.

11. The pharmaceutical dosage form of claim 1, comprising from about 10 wt. % to about 20 wt. % hydroxypropyl methylcellulose, from about 45 wt. % to about 50 wt. % hydroxypropyl cellulose, and about 4 wt. % to about 6 wt. % tannic acid.

12. A pharmaceutical dosage form for oral administration to a patient providing pulsed gastric release of methylphenidate comprising:

a) a gastric retention vehicle composition comprising about 20 wt-% to about 70 wt-% of a hydrogel, about 10 wt-% to about 75 wt-% superdisintegrant and about 2 wt-% to about 12 wt-% tannic acid, the percentages calculated exclusive of other excipients or the methylphenidate,

b) a first reservoir containing methylphenidate embedded in said gastric retention vehicle composition wherein methylphenidate is released from the first reservoir into the stomach upon contact of the dosage form with gastric fluid, and

c) a second reservoir containing methylphenidate embedded in said gastric retention vehicle composition, wherein the second reservoir is coated with a coating that is impermeable to methylphenidate and dissolves in gastric fluid, and, after a sufficient amount of the coating is dissolved, the methylphenidate is released from the second reservoir into the stomach, wherein, upon contact with gastric fluid the gastric retention vehicle composition expands to a sufficient degree such that the dosage form is retained in the stomach at least until methylphenidate is released from the second reservoir.

13. A pharmaceutical dosage form of claim 12 further comprising a third reservoir containing methylphenidate coated with a coating that is impermeable to methylphenidate and dissolves in gastric fluid, wherein the methylphenidate is released from the third reservoir into the stomach after the methylphenidate is released from the second reservoir.

14. A pharmaceutical dosage form of claim 12 wherein the first reservoir is coated with a coating that delays release of the methylphenidate from said first reservoir.

15. A pharmaceutical dosage form of claim 12 wherein the gastric retention vehicle composition and the reservoirs are encapsulated.

16. The pharmaceutical dosage form of claim 12, wherein the methylphenidate is released from the second reservoir about 3 to about 5 hours after administration.

17. A method of treating hyperactivity or attention deficit disorder comprising administering a therapeutically effective amount of methylphenidate in the pharmaceutical dosage form of claim 12 to a patient in need thereof.

18. The pharmaceutical dosage form of claim 12, wherein the coating comprises polymethacrylate, or a mixture of hydrophilic and hydrophobic film forming agents.

19. The pharmaceutical dosage form of claim 18, wherein the hydrophilic film forming agent is selected from the group consisting of methyl cellulose, hydroxypropyl methylcellulose, cellulose phthalate, cellulose acetate phthalate, and polyvinyl alcohol.

20. The pharmaceutical dosage form of claim 18, wherein the hydrophobic film forming agent is selected from the group consisting of ethyl cellulose, cellulose acetate, hydroxypropyl methylcellulose phthalate, polyvinyl alcohol maleic anhydride copolymers, β

-pinen polymers rosin, partially hydrogenated rosin, and glycerol esters of rosin.

21. The pharmaceutical dosage form of claim 12, wherein the superdisintegrant is selected from the group consisting of cross-linked carboxymethylcellulose sodium, sodium starch glycolate, and cross-linked polyvinyl pyrollidone.

22. The pharmaceutical dosage form of claim 12, wherein the hydrogel is hydroxypropyl methyl cellulose or a mixture of hydroxypropyl methyl cellulose and hydroxypropyl cellulose or a cross-linked acrylate polymer.

23. The pharmaceutical dosage form of claim 12, comprising from about 10 wt. % to about 30 wt. % hydroxypropyl methylcellulose, from about 40 wt. % to about 60 wt. % hydroxypropyl cellulose, and about 4 wt. % to about 12 wt. % tannic acid.

24. The pharmaceutical dosage form of claim 12, comprising from about 10 wt. % to about 20 wt. % hydroxypropyl methylcellulose, from about 45 wt. % to about 50 wt. % hydroxypropyl cellulose, and about 4 wt. % to about 6 wt. % tannic acid.