Delivery system with bilayer osmotic engine

• US 5,340,590 A
• Filed: 07/08/1993
• Issued: 08/23/1994
• 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, Huynh, Hoa T., Wong, Patrick S. L., Larsen, Steven D.
• Primary Examiner(s): Phelan, D. Gabrielle
• Application Number:
  US08/088,931
• Time in Patent Office: 411 Days
• Field of Search: 424/473, 424/472
• 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 9/4808 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: 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 which is capable of delivery of a plurality of discrete drug-containing units in any desired delivery pattern or profile.

Claims

1. An improved dispenser for the delivery of an active agent to a fluid-containing environment, the dispenser comprising, in combination:

a. a housing open at one end to provide outlet means therefor, at least a portion of said hosing proximate the end of said housing opposite the outlet means permitting passage of the fluid in said environment to the interior of said housing;

b. a fluid-activated driving means within said housing; and

;

c. a plurality of solid, discrete dosage units containing said active agent longitudinally disposed within said housing between said driving means and said outlet means, whereby said active agent units will be sequentially displaced from said housing into said fluid environment by said driving means upon exposure of said dispenser to said fluid environment;

wherein the improvement comprises said fluid-activated driving means comprising;

(1) a first member in fluid-transmitting relationship with the means for permitting the passage of fluid in the housing at the proximate the end of said housing opposite said outlet means, said first member being comprises of an osmotic material that absorbs sufficient fluid from said relatively low fluid-containing environment of use so that, upon exposure of said dispenser to said fluid environment, said first osmotic member is the source of motive power for moving the contents of said housing through said outlet means, and

(2) a second member between said first osmotic member and said active agent dosage units and comprised of an osmotic material which does not absorb onto or stick to said active agent units but expands to form a seal against the internal wall of said housing.

4. The improved dispenser of claim 1 wherein said first osmotic member is comprised of a mixture of an osmagent in an osmopolymer and said second osmotic member is comprised of an osmopolymer.

5. The improved dispenser of claim 1 wherein said environment of use is the colon.

2. An improved dispenser for the delivery of an active agent to a fluid-containing environment, the dispenser comprising, in combination:

a. a housing open at one end to provide outlet means therefor, at least a portion of said housing proximate the end of said housing opposite the outlet means permitting passage of the fluid in said environment to the interior of said housing;

b. a fluid-activated driving means within said housing; and

c. a plurality of solid, discrete dosage units containing said active agent longitudinally disposed within said housing between said driving means and said outlet means, whereby said active agent units will be sequentially displaced from said housing into said fluid environment by said driving means upon exposure of said dispenser to said fluid environment;

wherein the improvement comprises said fluid-activated driving means comprising;

(1) a first member in fluid-transmitting relationship with the means for permitting the passage of fluid in the housing at the proximate the end of said housing opposite said outlet means, said first member being comprises of an osmotic material so that, upon exposure of said dispenser to said fluid environment, said first osmotic member is the source of motive power for moving the contents of said housing through said outlet means, and

(2) a second member between said first osmotic member and said active agent dosage units and comprised of an osmotic material which does not absorb onto or stick to said active agent units but expands to form a seal against the internal wall of said housing.

6. The improved dispenser of claim 2 wherein said first osmotic member is comprised of a mixture of an osmagent in an osmopolymer and said second osmotic member is comprised of an osmopolymer.

7. The improved dispenser of claim 2 wherein the portion of said housing adjacent said active agent units is permeable to the fluid in said fluid environment.

8. The improved dispenser of claim 2 wherein said housing is formed from a material permeable to the fluid in said fluid environment.

9. The improved dispenser of claim 2 wherein the portion of said housing adjacent said active agent units is impermeable to the fluid in said fluid environment.

10. The improved dispenser of claim 2 wherein said active agent units are separated by non-active agent-containing units.

11. The improved dispenser of claim 2 which further comprises a rate-controlling membrane surrounding said housing and open at one end to provide outlet means.

3. A method for providing a pulsatile delivery of an active agent to a fluid-containing environment, the method comprising:

1) placing in said environment a dispenser comprising, in combination;

a. a housing open at one end to provide outlet means therefor, at least a portion of said housing proximate the end of said housing opposite the outlet means permitting passage of the fluid in said environment to the interior of said housing;

b. a fluid-activated driving means within said housing, said driving means comprising;

(i) a first member in fluid-transmitting relationship with the fluid-passing portion of said housing proximate the end of said housing opposite said outlet means, said first member being comprised of an osmotic material so that, upon exposure of said dispenser to said fluid environment, said first osmotic member is the source of motive power for moving the contents of said housing through said outlet means, and

(ii) a second member between said first member and a plurality of solid, discrete active agent dosage units and comprised of an osmotic material which does not absorb onto or stick to said active agent units but expands to form a seal against the internal wall of said housing; and

c. a plurality of solid, discrete dosage units containing said active agent longitudinally disposed within said housing between said driving means and said outlet means, at least a portion of said active agent units being adapted to maintain their chemical and physical integrity while within the housing and to dispense a substantial portion of their active agent content into the fluid environment after their displacement from said housing into said environment; and

(2) allowing fluid to be imbibed through said housing of said dispenser for causing said driving means to expand to sequentially displace said active agent dosage units from said housing into said fluid environment.