Multi-layer delivery system

• US 4,874,388 A
• Filed: 06/25/1987
• Issued: 10/17/1989
• Est. Priority Date: 06/25/1987
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Eckenhoff, James B., Theeuwes, Felix, Wong, Patrick S. L.
• Primary Examiner(s): Schwadron, Martin P.
• Assistant Examiner(s): Flanigan, Allen J.
• Application Number:
  US07/066,906
• Time in Patent Office: 845 Days
• Field of Search: 424/438, 604/93, 604/131, 604/890.1, 604/891.1, 604/892.1
• US Class Current: 604/891.1
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50

Abstract

A dispenser for use in a fluid environment having a rigid housing containing a fluid activated driving member, a plurality of drug containing layers and an outlet means by which drug is dispensed to the environment. The housing adjacent to the layers is fluid impermeable and the housing adjacent to the driving member is fluid permeable or has an open area by which fluid can contact the driving member. O048743884

Claims

1. A drug dispenser for use in a fluid-containing environment comprising, in combination:

a. a rigid housing having an outlet at one end thereof;

b. a fluid activated driving member within a portion of said housing proximate the end of said housing opposite to said outlet and in contact with said housing, at least that portion of the housing contacting the driving member having a predetermined permeation rate to the environmental fluid;

c. a first set of drug layers longitudinally disposed within said housing between said driving means and said outlet;

d. a second set of layers longitudinally disposed within said housing and alternating with said first drug layers; and

e. an expansion chamber defining an empty volume within said housing between the drug layer most proximate the outlet and the outlet;

whereby said drug layers must be displaced through the expansion chamber by said driving means after exposure of said dispenser to the fluid environment.

2. The dispenser of claim 1 wherein the portion of said rigid housing proximate said expansion means has a permeation rate to said environmental fluid substantially greater than the permeation rate of the portion of the housing proximate said driving means.

3. The dispenser of claim 2 wherein the portion of said housing between said driving means and said expansion means is substantially impermeable to said environmental fluid.

4. The dispenser of claim 3 wherein said first set of layers contains means for generating gas upon contact with said environmental fluid.

5. The dispenser of claim 1 wherein said second set of layers contains a drug different from the drug in said first set of layers and is formulated to release a substantial portion of its drug to the fluid environment after displacement through the outlet.

6. The dispenser of claim 1 wherein said plurality of drug layers contain different drugs.

7. The dispenser of claim 6 wherein said layers further comprise excipients to control the erosion of said layers.

8. The dispenser of claim 1 wherein said drug layers are separated by non-drug containing layers.

9. The dispenser of claim 1 wherein said driving member comprises a fluid swellable composition.

10. The dispenser of claim 1 wherein said driving member comprises an osmotically effective solute.

11. The dispenser of claim 10 wherein the portion of said housing in contact with said solute is permeable to the passage of fluid.

12. The dispenser of claim 11 wherein said solute and said drug layers are separated by a flexible membrane.

13. The dispenser of claim 1 wherein said driving member comprises an elementary osmotic pump.

14. The dispenser of claim 13 wherein said elementary osmotic pump and said drug layers are separated by a movable piston.

15. The dispenser of claim 1 wherein said driving member comprises a gas generating composition.

16. The dispenser of claim 15 wherein said gas generating composition and said drug layers are separated by a semipermeable membrane.

17. The dispenser of claim 1 which further comprises a density element.

18. The dispenser of claim 1 wherein said first set of layers deliver drug to the environment by bursting upon contact with said outlet means.

19. The dispenser of claim 18 wherein said first set of layers contain a drug selected from the group consisting of:

bithionol sulfoxide, oxyclozanide, clioxanide, niclofolan, nitroxinil, rafoxanide, benzimidazole and diamfenetide.

20. The dispenser of claim 18 wherein said second set of layers contain ivermectin suspended in wax.

21. The dispenser of claim 20 which further comprises a density element.

22. The dispenser of claim 4 wherein said first set of layers are comprised of a hydrophilic drug composition.

23. The dispenser of claim 22 wherein said second set of layers are comprised of a hydrophobic composition.

24. The dispenser of claim 22 wherein said hydrophilic drug composition is comprised of a drug and an osmotic agent.

25. The dispenser of claim 22 wherein said hydrophilic drug composition is comprised of a drug and a heat sensitive agent.

26. The dispenser of claim 23 wherein said hydrophobic composition further comprises a drug.