Oral pulsed dose drug delivery system

• US 6,322,819 B1
• Filed: 10/21/1998
• Issued: 11/27/2001
• Est. Priority Date: 10/21/1998
• Status: Expired

• Current Assignee: Shire LLC (Shire plc)
• Original Assignee: Shire Laboratories, Inc. (Supernus Pharmaceuticals Incorporated)
• Inventors: Treacy, Donald J., Fiske, Kimberly, McGuinness, Charlotte, Couch, Richard A., Chang, Rong-Kun, Rudnic, Edward M., Burnside, Beth A., Guo, Xiaodi
• Primary Examiner(s): Dudash, Diana
• Assistant Examiner(s): Berman, Alysia
• Application Number:
  US09/176,542
• Publication Number:
  US 20010055613A1
• Time in Patent Office: 1,133 Days
• Field of Search: 424/494, 424/457, 424/471, 424/472, 424/480, 424/497, 424/461, 424/462, 424/470, 424/458, 424/459, 424/460, 424/468, 424/482
• US Class Current: 424/494
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

A multiple pulsed dose drug delivery system for pharmaceutically active amphetamine salts, comprising an immediate-release component and an enteric delayed-release component wherein (1) the enteric release coating has a defined minimum thickness and/or (2) there is a protective layer between the pharmaceutically active amphetamine salt and the enteric release coating and/or (3) there is a protective layer over the enteric release coating. The product can be composed of either one or a number of beads in a dosage form, including either capsule, tablet, or sachet method for administering the beads.

Claims

1. A pharmaceutical composition for delivery of one or more pharmaceutically active amphetamine salts, comprising:

(a) one or more pharmaceutically active amphetamine salts covered with an immediate release coating; and

(b) one or more pharmaceutically active amphetamine salts that are covered with an enteric release coating that provides for delayed pulsed enteric release, wherein said enteric release coating releases essentially all of said one or more pharmaceutically active amphetamine salts coated with said enteric coating within about 60 minutes after initiation of said delayed pulsed enteric release.

2. The composition of claim 1 wherein said enteric release coating has a thickness of at least 25μ

.

3. The pharmaceutical composition of claim 1 wherein the one or more pharmaceutically active amphetamine salts are coated onto a core.

4. The pharmaceutical composition of claim 1 wherein the one or more pharmaceutically active amphetamine salts are incorporated into a core.

5. The pharmaceutical composition of claim 1 wherein the one or more pharmaceutically active amphetamine salts covered with an immediate release coating and the one or more pharmaceutically active amphetamine salts covered with an enteric release coating are present on a single core.

6. The pharmaceutical composition of claim 1 wherein the one or more pharmaceutically active amphetamine salts covered with an immediate release coating and the one or more pharmaceutically active amphetamine salts covered with an enteric release coating are present on different cores.

7. The composition of claim 1 wherein said enteric release coating is a non-pH dependent enteric release coating.

8. A pharmaceutical composition for delivery of at least one amphetamine salt, comprising:

(a) at least one pharmaceutically active amphetamine salt covered with an immediate release coating; and

(b) at least one pharmaceutically active amphetamine salt covered with an enteric release coating, said component (a) providing for an immediate release of amphetamine salt to provide a first blood level of amphetamine salt and component (b) providing a delayed pulse enteric release of amphetamine salt that increases the blood level of amphetamine salt to a second level that is greater than the first level provided by component (a), wherein said enteric release coating releases essentially all of said one or more pharmaceutically active amphetamine salts coated with said enteric coating within about 60 minutes after initiation of said delayed pulsed enteric release.

9. The pharmaceutical composition of claim 8 wherein the one or more pharmaceutically active amphetamine salts are coated onto a core.

10. The pharmaceutical composition of claim 8 wherein the one or more pharmaceutically active amphetamine salts are incorporated into a core.

11. The pharmaceutical composition of claim 8 wherein the one or more pharmaceutically active amphetamine salts covered with an immediate release coating and the one or more pharmaceutically active amphetamine salts covered with an enteric release coating are present on a single core.

12. The pharmaceutical composition of claim 8 wherein the one or more pharmaceutically active amphetamine salts covered with an immediate release coating and the one or more pharmaceutically active amphetamine salts covered with an enteric release coating are present on different cores.

13. A pharmaceutical composition for delivering one or more pharmaceutically active amphetamine salts comprising:

(a) one or more pharmaceutically active amphetamine salts covered with an immediate release coating;

(b) one or more pharmaceutically active amphetamine salts that are covered with an enteric release coating that provides for delayed pulsed enteric release, wherein said enteric release coating releases essentially all of said one or more pharmaceutically active amphetamine salts coated with said enteric coating within about 60 minutes after initiation of said delayed pulsed enteric release; and

(c) a protective layer over the enteric release coating.

14. The pharmaceutical composition of claim 13 wherein the one or more pharmaceutically active amphetamine salts are coated onto a core.

15. The pharmaceutical composition of claim 13 wherein the one or more pharmaceutically active amphetamine salts are incorporated into a core.

16. The pharmaceutical composition of claim 13 wherein the one or more pharmaceutically active amphetamine salts covered with an immediate release coating and the one or more pharmaceutically active amphetamine salts covered with an enteric release coating are present on a single core.

17. The pharmaceutical composition of claim 13 wherein the one or more pharmaceutically active amphetamine salts covered with an immediate release coating and the one or more pharmaceutically active amphetamine salts covered with an enteric release coating are present On different cores.

18. A pharmaceutical composition for delivery of one or more pharmaceutically active amphetamine salts comprising:

(a) one or more pharmaceutically active amphetamine salts covered with an immediate release coating;

(b) one or more pharmaceutically active amphetamine salts that are covered with an enteric release coating that provides for delayed pulsed enteric release, wherein said enteric release coating releases said one or more pharmaceutically active amphetamine salts coated with said enteric coating within about 60 minutes after initiation of said delayed pulsed enteric release; and

(c) a protective layer between the at least one pharmaceutically active amphetamine salt and the enteric release coating.

19. The pharmaceutical composition of claim 18 wherein The delayed pulsed release is from 4 to 6 hours after administration of the pharmaceutical composition.

20. The pharmaceutical composition of claim 18 wherein the delayed pulse enteric release, releases the amphetamine salt in about 30 to 60 minutes after initiation of the release.

21. The pharmaceutical composition of claim 18 wherein the one or more pharmaceutically active amphetamine salts are coated onto a core.

22. The pharmaceutical composition of claim 18 wherein the one or more pharmaceutically active amphetamine salts are incorporated into a core.

23. The pharmaceutical composition of claim 18 wherein the one or more pharmaceutically active amphetamine salts covered with an immediate release coating and the one or more pharmaceutically active amphetamine salts covered with an enteric release coating are present on a single core.

24. The pharmaceutical composition of claim 18 wherein the one or more pharmaceutically active amphetamine salts covered with an immediate release coating and the one or more pharmaceutically active amphetamine salts covered with an enteric release coating are present on different cores.