Osmotic system for the controlled and delivery of agent over time

• US 4,111,202 A
• Filed: 11/22/1976
• Issued: 09/05/1978
• Est. Priority Date: 11/22/1976
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Theeuwes, Felix
• Primary Examiner(s): Padgett, Benjamin R.
• Assistant Examiner(s): Gron, T. S.
• Application Number:
  US05/743,975
• Time in Patent Office: 652 Days
• Field of Search: 128/260, 128/261, 128/268, 128/272, 424/15, 424/19-22, 424/33, 424/37, 222/491, 222/395, 206/0.5, 222/193, 222/389, 222/130
• 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: A61K 9/0036 Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms

Abstract

An osmotic system for delivering a beneficial agent is disclosed. The system comprises a wall surrounding an agent compartment and an osmagent compartment separated by a film and has a passageway through the wall for delivering agent from its compartment. The wall is formed of a material permeable to the passage of an external fluid and impermeable to the passage of agent and osmagent. The film is formed of a material impermeable to the passage of agent and osmagent and movable from an original to an expanded state. The agent compartment contains an agent that is soluble in the fluid and exhibits an osmotic pressure gradient across the wall against the fluid, or the compartment contains an agent that has limited solubility in the fluid and exhibits a limited osmotic pressure gradient across the wall against fluid. The osmagent compartment contains an osmagent that exhibits an osmotic pressure gradient across the wall against the fluid. In operation, agent is delivered from the system through the passageway by fluid being imbibed through the wall into the osmagent compartment urging it to increase in volume and expand the film and correspondingly diminishing the volume of the agent compartment, whereby agent is released at a rate controlled by the permeability of the wall, the osmotic pressure gradient across the wall, and the expansion of the film over a prolonged period of time.

Claims

1. An osmotic therapeutic system for the controlled delivery of a beneficial drug to a biological environment, comprising:

a. a wall formed of a semipermeable material permeable to the passage of external fluid present in the environment and substantially impermeable to the passage of drugs and compounds;

the semipermeable wall surrounding and forming;

b. a first and second compartment, said first compartment containing a drug that is in direct communication with the semipermeable wall, said second compartment containing an osmotically effective compound that exhibits an osmotic pressure gradient across the semipermeable wall against the fluid, with the compartments separated by a flexible membrane, which membrane is substantially impermeable to the passage of drug, compound and fluid;

c. a passageway in the wall communicating with the compartment containing the drug for delivering drug from the system; and

,

d. wherein in operation when the system is in the environment of use, fluid from the environment is imbibed through the wall into (1) the first compartment containing drug in a tendency towards osmotic equilibrium at a rate determined by the permeability of the wall and the osmotic pressure gradient across the wall thereby forming a formulation containing drug, and into (2) the second compartment containing osmotic compound in a tendency towards osmotic equilibrium at a rate determined by the permeability of the wall and the osmotic pressure gradient across the wall thereby continuously filling the second compartment and expanding the membrane into the first compartment, whereby, through the combined actions of the first and second compartments, drug is delivered through the passageway from the system at a controlled rate over a prolonged period of time.

2. The osmotic therapeutic system for the controlled delivery of the beneficial drug according to claim 1, wherein the drug is a member selected from the group consisting of anticonvulsant, antiparkinson, analgesic, anti-inflammatory, anesthetic, hormonal, contraceptive, sympathomimetic, diuretic, ophthalmic, central nervous system, sedative, tranquilizer, anti-infective and hypoglycemic drugs.

3. The osmotic therapeutic system for the delivery of the beneficial drug according to claim 1, wherein the system is sized, shaped and adapted as a dosage form for delivering drug to the anal tract.

4. The osmotic therapeutic system for the delivery of drug according to claim 1, wherin the drug is a member selected from the group of drugs that have limited solubility in the fluid and exhibits a limited osmotic pressure gradient across the wall against the fluid, and drugs that are practically insoluble in the external fluid.

5. The osmotic therapeutic system for the delivery of the drug according to claim 1, wherein the compartment containing the drug also contains a compound that is soluble in the external fluid and exhibits an osmotic pressure gradient across the wall against the fluid.

6. The osmotic system for the controlled and continuous delivery of the beneficial drug according to claim 1, wherein the system is sized, shaped and adapted as a dosage form for delivering drug to the gastrointestinal tract.

7. The osmotic system for the controlled and continuous delivery of the drug according to claim 1, wherein the fluid imbibed into the second compartment containing the osmotic compound, dissolves the compound and increases the volume of said second compartment urging it to expand the membrane against the first compartment and correspondingly decrease the volume of the first compartment.

8. The osmotic system for the controlled and continuous delivery of the beneficial drug according to claim 1, wherein the fluid imbibed into the second compartment containing the osmotic compound increases the volume of the second compartment and expands the membrane into the drug compartment thereby concentrating the drug in the drug compartment.

9. An osmotic system for the controlled and continuous delivery of a beneficial agent to the environment of use comprising:

a. a shaped wall formed of a semipermeable material permeable to the passage of an external fluid in the environment of use and substantially impermeable to the passage of beneficial agent and compound, the shaped semipermeable wall surrounding and forming;

b. a first and second compartment, said compartments separated by an expandable membrane permeable to fluid and substantially impermeable to beneficial agent and compound, and wherein the first compartment contains a beneficial agent in communication with the semipermeable wall and the second compartment contains an osmotically effective compound that exhibits an osmotic pressure gradient directly across the semipermeable wall against the fluid;

c. a passageway in the semipermeable wall communicating with the beneficial agent compartment and the exterior of the system for delivering the beneficial agent from the system; and

,

d. wherein in operation, when the system is in the environment of use, fluid from the environment is imbibed through the semipermeable wall into (1) the first compartment containing the beneficial agent in a tendency towards osmotic equilibrium at a rate determined by the permeability of the wall and the osmotic pressure gradient across the wall, and into (2) the second comparment containing osmotically effective compound through the membrane at a rate determined by the permeability of the membrane and the osmotic pressure gradient across the membrane, said imbibitions increasing the volume of the second compartment and expanding the membrane into the compartment containing beneficial agent is delivered through the passageway from the system at a controlled rate over a prolonged period of time.

10. The osmotic system for the controlled and continuous delivery of the beneficial agent according to claim 9, wherein the beneficial agent is a member selected from the group consisting of an agent having limited solubility in the fluid and an agent that is practically insoluble in the fluid, and wherein said agents are mixed with an osmotically effective compound that is soluble in the fluid and exhibits an osmotic pressure gradient across the semipermeable wall against the fluid.

11. The osmotic system for the controlled and continuous delivery of beneficial agent according to claim 9, wherein the membrane is formed integral with the compartment containing the beneficial agent and serves as a wall of the compartment containing the osmotic compound.

12. The osmotic system for the controlled and continuous delivery of beneficial agent according to claim 9, wherein the membrane is formed integral with the compartment containing the osmotic compound and serves as a wall of the compartment containing the beneficial agent.

13. The osmotic system for the controlled and continuous delivery of the beneficial agent according to claim 9, wherein the beneficial agent is soluble to very soluble in the fluid and exhibits an osmotic pressure gradient across the wall against the fluid.

14. The osmotic system for the controlled and continuous delivery of the beneficial agent according to claim 9, wherein the system is sized, shaped and adapted for administering the beneficial agent to the gastrointestinal tract.

15. The osmotic system for the controlled and continuous delivery of the beneficial agent according to claim 9, wherein the semipermeable wall is formed of a member selected from the group of semipermeable materials consisting of cellulose acetate, cellulose diacetate, cellulose triacetate, polyurethane, polyamide, sulfonated polystyrene, cellulose acetate valerate, and cellulose acetate succinate.

16. The osmotic system for the controlled and continuous delivery of the beneficial agent according to claim 9, wherein the membrane contains from 0.01% to 40% of a member selected from the group consisting of polyalkylene glycol, preferably polyethylene glycol having a molecular weight of 300 to 6,000 of the formula H--(--OCH₂ CH₂)_n --OH wherein n is 5 to 204;

poly(α

,ω

)-alkylenediols;

polyester alkylene glycol; and

mixtures thereof.

17. The osmotic system for the controlled and continuous delivery of the beneficial agent according to claim 9, wherein the semipermeable wall is thicker than the membrane and imbibition of fluid by the osmotically effective compound is accompanied by an expansion of the membrane as fluid continuously fills the osmotic compound compartment and exerts force against the membrane.

18. The osmotic system for the controlled and continuous delivery of the beneficial agent according to claim 9, wherein the membrane surrounds the compartment containing the beneficial agent and has a surface adjacent to the compartment containing the osmotic compound, and wherein the membrane is formed of a material permeable to the passage of fluid, impermeable to the passage of beneficial agent and osmotic compound, and is movable from an original position to an expanded position.

19. The osmotic system for the controlled and continuous delivery of the beneficial agent according to claim 9, wherein the membrane surrounds the compartment containing the osmotic compound and has a surface adjacent to the compartment containing the beneficial agent, and wherein the membrane is formed of a material permeable to the passage of fluid, impermeable to the passage of beneficial agent and osmotic compound, and is movable from an original position to an expanded position.

20. The osmotic system for the controlled and continuous delivery of the beneficial agent according to claim 9, wherein the membrane is positioned between the beneficial agent and the osmotic compound compartments, and wherein the membrane contains an expansion agent that imparts flexibility and expandability to the membrane and is selected from the group consisting of phthalates, phosphates, citrates, adipates, tartrates, sebacates, succinates, glycolates, glycerolates, benzoates, and myristates.

21. The osmotic system for the controlled and continuous delivery of the beneficial agent according to claim 9, wherein the beneficial agent is a member selected from the group consisting of pesticides, herbicides, germicides, fungicides, insecticides and algicides.

22. An osmotic system sized, shaped and adapted for placement in an environment of use, comprising:

a. a shaped wall formed of a non-toxic semipermeable material permeable to the passage of fluid present in the environment of use and substantially impermeable to the passage of beneficial agent and osmotically effective agent;

b. the semipermeable wall surrounding and forming a compartment housing a membrane that divides the compartment into an area containing beneficial agent in contact with the semipermeable wall and an area containing an osmotically effective agent in contact with the semipermeable wall;

c. a passageway in the wall communicating with the area containing the beneficial agent for delivering said beneficial agent from the system; and

,

d. wherein in operation, when the system is in the environment, fluid is imbibed through the semipermeable wall into the areas in a tendency towards osmotic equilibrium at a rate determined by the permeability of the semipermeable wall and the osmotic pressure gradient across the semipermeable wall thereby delivering beneficial agent through the passageway from the system, with the amount of beneficial agent delivered from the system related to the volume of fluid imbibed into the area containing the beneficial agent and the volume of fluid imbibed into the area containing the osmotically effective agent over a prolonged period of time.

23. The osmotic system sized, shaped and adapted for placement in an environment of use according to claim 22, wherein as the area containing the osmotic agent continuously increases in volume, the area containing the beneficial agent correspondingly diminishes in volume, and wherein the beneficial agent is a drug which is delivered from the system at a controlled rate over a prolonged period of time.

24. The osmotic system sized, shaped and adapted for placement in an environment of use according to claim 22, wherein the beneficial agent is present in the area as a solid, gel, paste, semisolid, cream or emulsion, which beneficial agent is mixed with fluid imbibed into the area for delivery through the passageway from the area at a controlled rate over a prolonged period of time.

25. The osmotic system for placement in the environment according to claim 22, wherein the beneficial agent exhibits a solubility of from practically insoluble to very soluble in the fluid and is mixed with an osmotically effective agent that exhibits an osmotic pressure gradient across the semipermeable wall against the fluid.

26. The osmotic system for placement in the environment according to claim 22, wherein the environment is a biological environment and the beneficial agent is a member selected from the group consisting of corticosteroids, androgens, estrogens and progestational steroids.