Methods and devices for providing prolonged drug therapy

• US 20010012847A1
• Filed: 03/08/2001
• Published: 08/09/2001
• Est. Priority Date: 11/12/1996
• Status: Active Grant

• Current Assignee: Andrew C. Lam, Atul D. Ayer, Carol A. Christopher, Diane R. Guinta, Jeri D. Wright, Lawrence G. Hamel, Padmaja Shivanand, Richard G. Weyers, Samuel R. Saks, Suneel K. Gupta, Zahedeh Hatamkhany
• Original Assignee: Andrew C. Lam, Atul D. Ayer, Carol A. Christopher, Diane R. Guinta, Jeri D. Wright, Lawrence G. Hamel, Padmaja Shivanand, Richard G. Weyers, Samuel R. Saks, Suneel K. Gupta, Zahedeh Hatamkhany
• Inventors: Gupta, Suneel K., Ayer, Atul D., Saks, Samuel R., Guinta, Diane R., Hamel, Lawrence G., Christopher, Carol A., Lam, Andrew C., Shivanand, Padmaja, Hatamkhany, Zahedeh, Wright, Jeri D., Weyers, Richard G.
• Granted Patent: US 6,930,129 B2
• Time in Patent Office: Days
• US Class Current: 514/317
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/421 1,3-Oxazoles, e.g. pemoline, trimethadione
• CPC Class Codes: A61K 31/4422 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 9/0002 Galenical forms characterised by the drug release technique; Application systems commanded by energy
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• 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 9/2086 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 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61K 9/70 Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug hollow drug-filled fibres A61K9/0092

Abstract

Methods and devices for maintaining a desired therapeutic drug effect over a prolonged therapy period are provided. In particular, oral dosage forms that release drug within the gastrointestinal tract at an ascending release rate over an extended time period are provided. The dosage forms may additionally comprise an immediate-release dose of drug.

Claims

1. A method for treating a condition with a drug indicated for treatment of said condition, the method comprising the step of orally administering a dosage form containing said drug in a pharmaceutically acceptable carrier wherein said dosage form releases said drug from said dosage form at an ascending release rate for an extended time period.

2. The method described in

claim 1

wherein said dosage form is an osmotic dosage form comprising:

(a) a longitudinally compressed tablet core containing a plurality of layers wherein drug is contained in at least one layer and at least one other layer comprises a suitable fluid-expandable polymer;

(b) a semipermeable wall surrounding said longitudinally compressed tablet core to thereby form a compartment having an osmotic gradient to drive fluid from an external fluid environment contacting said semipermeable wall into said compartment; and

(c) an orifice formed through said semipermeable wall and into said longitudinally compressed tablet core to permit drug to be released from within said compartment into said external fluid environment.

3. The method described in

claim 2

wherein said longitudinally compressed tablet core comprises two layers and said drug is contained within a first layer and said fluid-expandable polymer is contained within a second layer and further wherein said orifice is formed through said semipermeable wall at a location adjacent to said first layer.

4. The method described in

claim 3

wherein said osmotic dosage form additionally comprises an immediate-release dose of a drug applied as a coating onto the outer surface of said osmotic dosage form.

5. The method described in

claim 2

wherein said longitudinally compressed tablet core comprises three layers and a portion of said drug is contained within a first layer and the remaining portion of said drug is contained within a second layer, wherein the concentration of drug contained within said first layer is less than the concentration of drug contained within said second layer, and wherein said fluid-expandable polymer is contained within a third layer and said orifice is formed through said semipermeable wall at a location adjacent to said first layer.

6. The method described in

claim 5

wherein said osmotic dosage form additionally comprises an immediate-release dose of a drug applied as a coating onto the outer surface of said osmotic dosage form.

7. A method for treating ADHD, the method comprising the step of orally administering a dosage form containing a CNS-acting drug in a pharmaceutically acceptable carrier wherein said dosage form releases said CNS-acting drug from said dosage form at an ascending release rate for an extended time period.

8. The method described in

claim 7

wherein said CNS-acting drug is a CNS-stimulant drug selected from the group consisting of methylphenidate, d-threo-methylphenidate, amphetamine, dextroamphetamine, methamphetamine, phenylisopropylamine and pemoline.

9. The method described in

claim 8

wherein said CNS-stimulant drug is methylphenidate.

10. The method described in

claim 9

wherein said dosage form is an osmotic dosage form comprising:

(a) a longitudinally compressed tablet core containing a plurality of layers wherein methylphenidate is contained in at least one layer and at least one other layer comprises a suitable fluid-expandable polymer;

(b) a semipermeable wall surrounding said longitudinally compressed tablet core to thereby form a compartment having an osmotic gradient to drive fluid from an external fluid environment contacting said semipermeable wall into said compartment; and

(c) an orifice formed through said semipermeable wall and into said longitudinally compressed tablet core to permit methylphenidate to be released from within said compartment into said external fluid environment.

11. The method described in

claim 10

wherein said longitudinally compressed tablet core comprises two layers and said methylphenidate is contained within a first layer and said fluid-expandable polymer is contained within a second layer and further wherein said orifice is formed through said semipermeable wall at a location adjacent to said first layer.

12. The method described in

claim 11

wherein said osmotic dosage form additionally comprises an immediate-release dose of methylphenidate applied as a coating onto the outer surface of said osmotic dosage form.

13. The method described in

claim 10

wherein said longitudinally compressed tablet core comprises three layers and a portion of said methylphenidate is contained within a first layer and the remaining portion of said methylphenidate is contained within a second layer, wherein the concentration of methylphenidate contained within said first layer is less than the concentration of methylphenidate contained within said second layer, and wherein said fluid-expandable polymer is contained within a third layer and said orifice is formed through said semipermeable wall at a location adjacent to said first layer.

14. The method described in

claim 13

wherein said osmotic dosage form additionally comprises an immediate-release dose of methylphenidate applied as a coating onto the outer surface of said osmotic dosage form.

15. A method for effectively treating ADHD for a prolonged therapy period of at least about 10 hours comprising administering methylphenidate in a dosage form that provides release of methylphenidate at an ascending release rate over an extended time period.

16. A method for providing plasma methylphenidate concentrations that are substantially smoothly ascending over an extended time period comprising administering methylphenidate in a dosage form that provides release of methylphenidate at an ascending release rate over an extended time period.

17. A dosage form comprising a drug in a pharmaceutically acceptable carrier wherein, following oral administration, said dosage form releases said drug from said dosage form at an ascending release rate for an extended time period.

18. The dosage form described in

claim 17

wherein said dosage form is an osmotic dosage form comprising:

(a) a longitudinally compressed tablet core containing a plurality of layers wherein said drug is contained in at least one layer and at least one other layer comprises a suitable fluid-expandable polymer;

(b) a semipermeable wall surrounding said longitudinally compressed tablet core to thereby form a compartment having an osmotic gradient to drive fluid from an external fluid environment contacting said semipermeable wall into said compartment; and

(c) an orifice formed through said semipermeable wall and into said longitudinally compressed tablet core to permit drug to be released from within said compartment into said external fluid environment.

19. The dosage form described in

claim 18

wherein said longitudinally compressed tablet core comprises two layers and said drug is contained within a first layer and said fluid-expandable polymer is contained within a second layer and further wherein said orifice is formed through said semipermeable wall at a location adjacent to said first layer.

20. The dosage form described in

claim 19

wherein said osmotic dosage form additionally comprises an immediate-release dose of a drug applied as a coating onto the outer surface of said osmotic dosage form.

21. The dosage form described in

claim 18

wherein said longitudinally compressed tablet core comprises three layers and a portion of said drug is contained within a first layer and the remaining portion of said drug is contained within a second layer, wherein the concentration of drug contained within said first layer is less than the concentration of drug contained within said second layer, and wherein said fluid-expandable polymer is contained within a third layer and said orifice is formed through said semipermeable wall at a location adjacent to said first layer.

22. The dosage form described in

claim 21

wherein said osmotic dosage form additionally comprises an immediate-release dose of a drug applied as a coating onto the outer surface of said osmotic dosage form.

23. A dosage form containing a CNS-acting drug in a pharmaceutically acceptable carrier wherein said dosage form, following oral administration, releases said CNS-acting drug from said dosage form at an ascending release rate for an extended time period.

24. The dosage form described in

claim 23

wherein said CNS-acting drug is a CNS-stimulant drug selected from the group consisting of methylphenidate, d-threo-methylphenidate, amphetamine, dextroamphetamine, methamphetamine, phenylisopropylamine and pemoline.

25. The dosage form described in

claim 24

wherein said CNS-stimulant drug is methylphenidate.

26. The dosage form described in

claim 25

wherein said dosage form is an osmotic dosage form comprising:

(a) a longitudinally compressed tablet core containing a plurality of layers wherein methylphenidate is contained in at least one layer and at least one other layer comprises a suitable fluid-expandable polymer;

(b) a semipermeable wall surrounding said longitudinally compressed tablet core to thereby form a compartment having an osmotic gradient to drive fluid from an external fluid environment contacting said semipermeable wall into said compartment; and

(c) an orifice formed through said semipermeable wall and into said longitudinally compressed tablet core to permit methylphenidate to be released from within said compartment into said external fluid environment.

27. The dosage form described in

claim 26

wherein said longitudinally compressed tablet core comprises two layers and said methylphenidate is contained within a first layer and said fluid-expandable polymer is contained within a second layer and further wherein said orifice is formed through said semipermeable wall at a location adjacent to said first layer.

28. The dosage form described in

claim 27

wherein said osmotic dosage form additionally comprises an immediate-release dose of methylphenidate applied as a coating onto the outer surface of said osmotic dosage form.

29. The dosage form described in

claim 26

wherein said longitudinally compressed tablet core comprises three layers and a portion of said methylphenidate is contained within a first layer and the remaining portion of said methylphenidate is contained within a second layer, wherein the concentration of methylphenidate contained within said first layer is less than the concentration of methylphenidate contained within said second layer, and wherein said fluid-expandable polymer is contained within a third layer and said orifice is formed through said semipermeable wall at a location adjacent to said first layer.

30. The dosage form described in

claim 29

wherein said osmotic dosage form additionally comprises an immediate-release dose of methylphenidate applied as a coating onto the outer surface of said osmotic dosage form.

31. The dosage form described in

claim 30

wherein said coating comprises an antidegradation agent.

32. The dosage form described in

claim 31

wherein said antidegradation agent is phosphoric acid.

33. The dosage form described in

claim 29

wherein said semipermeable membrane comprises cellulose acetate and a flux-enhancing agent.

34. The dosage form described in

claim 33

wherein said flux-enhancing agent is a copolymer of ethylene and propylene oxide.