System with microporous releasing diffusor

• US 4,309,996 A
• Filed: 04/28/1980
• Issued: 01/12/1982
• Est. Priority Date: 04/28/1980
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Theeuwes, Felix
• Primary Examiner(s): ROSENBAUM, C FRED
• Application Number:
  US06/144,210
• Time in Patent Office: 624 Days
• Field of Search: 128/127, 128/130, 128/260, 424/19, 424/22
• US Class Current: 604/892.1
• 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 system is disclosed for delivering a beneficial agent at a substantially constant rate over time. The system comprises (1) a wall formed of a microporous polymer, or (2) a wall formed in part of a microporous polymer with the remaining part of the wall formed of a semipermeable polymer. The wall in (1) surrounds a compartment comprising a flexible partition that separates the compartment into a first space containing the beneficial agent and a second space containing a swellable polymer. The wall in (2) surrounds a compartment comprising a flexible partition that separates the compartment into a first space in contact with the microporous wall and containing the beneficial agent, and a second space in contact with the semipermeable polymer containing an osmotically effective solute, or a swellable polymer. In operation, agent is delivered from the system by (a) fluid diffusing through the microporous wall into the second space causing the polymer to swell, or by (b) fluid being imbibed through the semipermeable wall into the second space causing the solute to dissolve and form a solution, or causing the polymer to swell, wherein in (a) or (b), the second space expands against the partition urging it to move into the first space and maintain the agent in a saturated state at the microporous wall, with the agent diffusing from the first space through fluid filled micropaths in the wall from the system at a substantially zero order rate over a prolonged period of time.

Claims

1. A system for the controlled delivery of a beneficial agent to an environment of use, the system comprising:

a. a wall having a plurality of micropaths through the wall, the wall surrounding and forming;

b. an internal compartment;

c. a flexible partition in the compartment joined to the wall, said partition forming a first internal space and a second internal space within the compartment;

d. a beneficial agent in the first space; and

,

e. means in the second space for increasing the volume of said second space, which means are a member selected from the group consisting essentially of an osmotically effective solute and a swellable lightly cross-linked polymer.

2. The system for the controlled delivery of the beneficial agent according to claim 1, wherein the micropaths in the wall are formed when the system is in the environment of use, which micropaths are connected to a multiplicity of micropores in the wall.

3. The system for the controlled delivery of the beneficial agent according to claim 1, wherein when the device is in the environment of use, the micropaths fill with fluid present in the environment, and the agent in the system diffuses through the fluid filled paths to the exterior of the system.

4. The system for the controlled delivery of the beneficial agent according to claim 1, wherein in operation when the system is in a fluid environment, agent is delivered from the system by diffusion through fluid filled micropaths in the wall, with the member absorbing fluid into the second space, expanding, continuously filling the space and moving against the partition, urging it to expand into the first space for substantially maintaining the concentration of agent in a saturated phase at the microporous wall, thereby, delivering agent at a zero order rate over an increased length of time.

5. The system for the controlled delivery of the beneficial agent according to claim 1, wherein the partition is formed of a semipermeable polymer selected from the group consisting of a cellulose ester, cellulose ether, cellulose acylate, cellulose diacylate, and cellulose triacylate.

6. The system for the controlled delivery of the beneficial agent according to claim 1, wherein the partition is formed of a polymer impermeable to the passage of agent, solute, polymer and fluid.

7. The system for the controlled delivery of the agent according to claim 1, wherein the agent is a drug selected from the group consisting of local acting drugs and systemic acting drugs.

8. The system for the controlled delivery of the agent according to claim 1, wherein the agent is a drug, the environment is the gastrointestional tract, and the system is manufactured as a device sized, shaped and adapeted for orally administering the drug to the gastrointestional tract.

9. The system for the controlled delivery of the agent according to claim 1, wherein the agent is a drug, the environment is a body passageway, and the system is sized, shaped and structured for easy placement and prolonged retention in the body passageway.

10. The system for the controlled delivery of the beneficial agent according to claim 1, wherein the partition contains a plasticizer.

11. The system for the controlled delivery of the beneficial agent according to claim 1, wherein the swellable polymer is lightly cross-linked and is a member selected from the group consisting of poly(hydroxyalkyl methacrylate), poly(acrylamide), poly(N-vinyl-pyrrolidone), anionic hydrogels, cationic hydrogels, and water-insoluble hydrophilic polymers.

12. The system for the controlled delivery of the beneficial agent at a controlled rate according to claim 1, wherein the wall is formed of a microporous polymer selected from the group consisting of poly(urethane), poly(imides), poly(sulfone), and poly(saccharides).

13. The system for the controlled delivery of the beneficial agent according to claim 1, wherein the micropaths in the wall are formed by removing a pore-former having size of about 100 angstroms to 200 microns.

14. A process for manufacturing a device for dispensing a useful agent, which device delays the appearance of a receding diffusional boundary layer when the device is dispensing the agent in an environment of use, the process comprising the steps of:

a. shaping and compressing and amount of the useful agent into a preselected shape;

b. shaping a swellable and expandable polymer into dimensions corresponding to the shaped agent;

c. placing a partition formed of a flexible polymer between the shaped agent and the shaped swellable polymer;

d. positioning the shaped agent and the shaped polymer in contacting relation with the partition; and

,

e. surrounding the shaped agent and the shaped polymer with a microporous wall to yield the device.

15. A process for delaying the appearance of a receding diffusional boundary layer in a device that dispenses a beneficial agent to an environment of use, wherein the device comprises:

a. microporous wall surrounding and forming;

b. a compartment;

c. a flexible partition in the compartment joined to the wall, said partition dividing the compartment into a first space and a second space;

d. a beneficial agent in the first space;

e. a volume generating agent in the second space, said volume generating agent a member selected from an osmotically effective solute and a expandable, swellable lightly cross-linked polymer; and

wherein the process for delaying the apearance of the receding boundary comprises;

1. expanding the volume generating agent in the second space to increase the volume of the second space causing it to move the partition into the first space and correspondingly diminish the volume occupied by the first space;

thereby,

2. maintaining the beneficial agent in a saturated state at the microporous wall for an increased length of time, which state delays the appearance of the receding diffusional boundary layer.

16. A diffusor for the controlled and continuous delivery of a beneficial agent at a zero order rate of release for an increased length of time to a fluid environment of use, the diffusor comprising;

a. a wall having a multiplicity of micropaths therethrough, the wall surrounding and forming;

b. a compartment having an internal space;

c. a beneficial agent in the compartment occupying part of the space;

d. a expandable polymer in the compartment occupying the remainder of the space;

e. a flexible partition in the compartment united to the wall and placed between the beneficial agent and the expandable polymer; and

,

f. wherein, when the diffussor is in the fluid environment, fluid fills the micropaths and enters space occupied by the expandable polymer, which absorbs the fluid causing it to expand against the partition, causing the partition to push the beneficial agent towards the wall, for keeping it in a saturated state, thereby increasing the length of time the beneficial agent is released from the diffusion at a zero order rate of release.

17. The diffusor for the controlled and continuous delivery of agent according to claim 16, wherein the environment of use is a human, the fluid is a biological fluid, the agent is a drug, and the diffusor is sized, shape and structured for placement and retention in said environment.

18. The diffusor for the controlled and continuous delivery of agent according to claim 16, wherein the micropaths in the wall are formed in the environment of use by fluid leaching a pore-former from the wall.

19. The diffusor for the controlled and continuous delivery of a beneficial agent according to claim 16, wherein the agent is a member selected from the group consisting of tranquilizers, psycic energizers, analgesics, antipyretics, anti-inflammatories, hormones, oral drugs, vaginal drugs and ano-rectal drugs.