Controlled release drug delivery device

• US 5,681,584 A
• Filed: 03/22/1996
• Issued: 10/28/1997
• Est. Priority Date: 04/23/1993
• Status: Expired due to Term

• Current Assignee: Ciba-Geigy Corporation (Novartis Ag)
• Original Assignee: Ciba-Geigy Corporation (Novartis Ag)
• Inventors: Shah, Shailesh, Carr, James, Quadros, Elizabeth, Khanna, Satish Chaudra, Savastano, Louis
• Primary Examiner(s): Phelan, D. Gabrielle
• Application Number:
  US08/622,238
• Time in Patent Office: 585 Days
• Field of Search: 424/473, 424/468
• US Class Current: 424/473
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• 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 9/2886 having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer of the type active core-drug layer-inactive layer A61K9/209

Abstract

A drug delivery device for delivering a drug either intermittently or to a pre-selected region of the gastro-intestinal tract, particularly to the colon, consists of an a solid core comprising an active agent coated with a delay jacket, then coated with a semi-permeable membrane which is optionally drilled to provide a release orifice, and then optionally further coated with an enteric material. The device delivers substantially all of the active agent to the targeted site.

Claims

1. A drug delivery device which comprises:

a) a solid core comprising a pharmaceutical or veterinary active agent;

b) a substantially soluble delay jacket coated over the core through which the active agent can diffuse, the delay jacket comprising at least one component selected from the group consisting of a binder, an osmotic agent, and a lubricant;

c) a semi-permeable membrane coated over the delay jacket and

d) an additional layer of active agent.

2. The device of claim 1, further comprising an enteric coating over the semi-permeable membrane.

3. The device of claim 1, wherein the semi-permeable membrane has a release orifice.

4. The device of claim 1, wherein the active agent is selected from the group consisting of proteins, peptides, antiasthmatics, antianginals, corticosteroids, 5-lipoxygenase inhibitors, antihypertensives, and leukotriene B₄ receptor antagonists.

5. The device of claim 1, wherein the active agent is selected from the group consisting of theophylline, IGF-I, PTH (1-34), TGF.sub.α

,TGF.sub.β

1, TGF.sub.β

2,TGFβ

₃,IFN.sub.α

, hybrid IFN.sub.α

, IFN.sub.γ

, hirudin, heparin, calcitonin, 5-aminosalicylic acid, N-hydroxy-N-((6-phenoxy-2H-1-benzopyran-3-yl)methyl)-urea, 4- 5- 4-(aminoiminomethyl)phenoxy!pentoxy!-3-methoxy-N,N-bis(1-methylethyl)benzamide (Z)-2-butenedioate, N- 2- 2- 4-(4-fluorophenyl)phenyl!methyl!-1,2,3,4-tetrahydro-1-oxo-6-isoquinolinyl!oxy!ethyl!-N-hydroxyurea, 1-(1-benzo b!thien-2-ylethyl)-1-hydroxyurea, 5- 2-(2-carboxyethyl)-3-{6-(para-methoxyphenyl)-5E-hexenyl}oxyphenoxy! valeric acid, beclomethasone dipropionate, betamethasone-17-valerate, prednisolone metasulfobenzoate, tixocortol pivalate, budesonide, fluticasone, and metoprolol, or pharmaceutically acceptable salts thereof.

6. The device of claim 1, wherein the delay jacket limits the release of the active agent from the drug core to no more than 10% for three hours in intestinal fluid.

7. The device of claim 1, wherein the delay jacket comprises an osmotic agent.

8. The device of claim 7, wherein the delay jacket further comprises at least one excipient selected from the group consisting of a binder, a hygroscopic suspending or thickening agent, and a tablet lubricant.

9. The device of claim 1, wherein the semi-permeable membrane comprises a compound selected from the group consisting essentially of cellulose acetate, ethylcellulose, polymethacrylic acid esters and acrylic acid ester/methacrylic acid copolymer, the copolymer having quarternary ammonium groups.

10. The device of claim 1, wherein the semi-permeable membrane comprises at least one aqueously dispersible pharmaceutically acceptable polymeric compound.

11. The device of claim 10, wherein the compound is selected from the group consisting of methacrylic ester copolymers, poly(ethyl acrylate, methyl methacrylate), poly(ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride), polymethyl methacrylate-methacrylic acid copolymers, cellulose acetate, ethylcellulose, cellulose acetate phthalate, and hydroxypropyl methylcellulose phthalate.

12. The device of claim 2, wherein the enteric coating is selected from the group consisting of cellulose acetate phthalate NF, hydroxypropyl methylcellulose phthalate NF, polyvinyl acetate phthalate NF, and methacrylic acid copolymer NF.

13. The device of claim 2, wherein the additional layer of active agent is between the semi-permeable membrane and the enteric coating.

14. The device of claim 2, wherein the additional layer of active agent is over the enteric coating.

15. The device of claim 3, wherein the release orifice is between about 0.05 mm and 1.5 mm.

16. The device of claim 2, wherein at least 50% of the active agent is delivered to the colon.

17. The device of claim 1, wherein the additional layer of active agent is between the delay jacket and the semi-permeable membrane.

18. A method of delivering an active agent to the lower portion of the small intestine of an animal in need thereof, said method consisting of orally administering the device of claim 2 to said animal.

19. A method of delivering a colonically active or colonically absorbable active agent to the colon of an animal in need thereof, said method consisting of orally administering the device of claim 2 to said animal.

20. The method of claim 19, wherein the active agent is delivered at a rate of from about 5% to about 25% by weight per hour in the colon.

21. A method of making an orally administrable active agent delivery device which comprises:

a) forming a solid core comprising a pharmaceutical or veterinary active agent;

b) coating said core with a substantially soluble delay jacket through which the active agent can diffuse, the delay jacket comprising at least one component selected from the group consisting of a binder, an osmotic agent, and a lubricant;

c) coating said delay jacket with a semi-permeable membrane; and

d) adding an additional layer of active agent, said additional layer of active agent being;

i) between the delay jacket and the semi-permeable membrane;

or

ii) outside of the semi-permeable membrane.

22. The method according to claim 21, wherein the semi-permeable membrane is applied as aqueous dispersion.

23. A method of making an orally administrable active agent delivery device which comprises:

a) forming a solid core comprising a pharmaceutical or veterinary active agent;

b) coating said core with a substantially soluble delay jacket through which the active agent can diffuse, the delay jacket comprising at least one component selected from the group consisting of a binder, an osmotic agent, and a lubricant;

c) coating said delay jacket with a semi-permeable membrane;

d) coating said semi-permeable membrane with an enteric coating; and

e) adding an additional layer of active agent, said additional layer of active agent being;

i) between the delay jacket and semi-permeable membrane;

ii) between the semi-permeable membrane and the enteric coating;

or

iii) outside of the enteric coating.