Diffusional implantable delivery system

• US 5,972,369 A
• Filed: 03/30/1998
• Issued: 10/26/1999
• Est. Priority Date: 03/31/1997
• Status: Expired due to Fees

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Tzannis, Stelios T., Roorda, Wouter E., Brown, James E., Wright, Jeremy C., Dionne, Keith E., Davis, Craig R., Prestrelski, Steven J.
• Primary Examiner(s): Azpuru, Carlos A.
• Application Number:
  US09/050,101
• Time in Patent Office: 575 Days
• Field of Search: 424/424, 424/425, 604/892.1
• US Class Current: 424/424
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61P 31/18 for HIV

Abstract

A sustained release delivery system for delivering a beneficial agent is provided. The system includes a reservoir comprising the beneficial agent and a capillary channel in communication with the reservoir and the exterior of the system for delivering the beneficial agent from the system. The capillary channel has a cross-sectional area and a length selected to deliver the beneficial agent at a predetermined rate. The system may further include an outer surface that is impermeable and non-porous during delivery of the beneficial agent. The beneficial agent may be formulated in a glassy sugar matrix.

Claims

1. A sustained release diffusional delivery system comprising:

a beneficial agent;

a reservoir that encloses said beneficial agent, an entirety of said reservoir that encloses said beneficial agent being impermeable and non-porous to fluids external of said reservoir during delivery of the beneficial agent; and

a capillary channel in communication with said reservoir and the exterior of the system for delivering said beneficial agent from the system;

said capillary channel having a cross-sectional area and a length selected to provide a predetermined delivery rate of said beneficial agent.

2. The system according to claim 1, wherein said beneficial agent is cidofovir.

3. The system according to claim 1, wherein said beneficial agent is a protein or peptide.

4. The system according to claim 3, wherein said protein is occluded in a glassy sugar matrix.

5. The system according to claim 1, wherein said capillary channel is filled with said beneficial agent.

6. The system according to claim 1, wherein said capillary channel is filled with an immobilized gel capable of diffusing said beneficial agent from said reservoir to the exterior of the system.

7. The system according to claim 1, wherein said capillary channel is filled with water.

8. The system according to claim 1, wherein said outer surface is selected from the group consisting of metals, ceramics, glass, and polymers.

9. The system according to claim 8, wherein said outer surface is a bioerodible polymer.

10. The system according to claim 9, wherein said bioerodible polymer is selected from the group consisting of poly(glycolic acid), poly(lactic acid), copolymers of lactic/glycolic acid, polyorthoesters, polyanhydrides, polyphosphazones, and polycaprolactones.

11. The system according to claim 8, wherein said non-porous material is titanium or a titanium alloy.

12. The system according to claim 1, wherein said capillary channel is helical.

13. The system according to claim 1, wherein said system is capable of being implanted into a mammalian organism.

14. The system according to claim 13, further comprising a ring at one end thereof for affixing said system inside said mammalian organism.

15. The system according to claim 1, wherein said system is capable of continuously delivering from about 0.5 to about 2 μ

g/day of said beneficial agent.

16. The system according to claim 1, wherein said system is capable of continuously delivering said beneficial agent over a period of at least two years.

17. The system according to claim 1, wherein said capillary channel has a diameter of about 0.01 mm to about 1 mm.

18. The system according to claim 1, wherein said capillary channel has a length of about 0.1 cm to about 25 cm.

19. The system according to claim 1, having a cylindrical shape.

20. The system according to claim 19, having a diameter of about 0.1 mm to about 10 mm, and a length of about 1 mm to about 50 mm.

21. A sustained release delivery system for delivering a beneficial agent formulated in a glassy sugar matrix at a predetermined rate, comprising:

(a) a reservoir comprising said beneficial agent formulated in a glassy sugar matrix; and

(b) a capillary channel in communication with said reservoir and the exterior of the system for delivering said beneficial agent from the system,

said capillary channel having a cross-sectional area and a length selected to provide said predetermined rate.

22. The system according to claim 21, wherein said beneficial agent is a protein or peptide.

23. The system according to claim 22, wherein said system is made of a bioerodible polymer.

24. The system according to claim 23, wherein said bioerodible polymer is selected from the group consisting of poly(glycolic acid), poly(lactic acid), copolymers of lactic/glycolic acid, polyorthoesters, polyanhydrides, polyphosphazones, and polycaprolactones.

29. The system according to claim 21, wherein said reservoir encloses said beneficial agent, an entirety of said reservoir that encloses said beneficial agent being impermeable and non-porous to fluids external of said reservoir during delivery of said beneficial agent.

25. A method of delivering a beneficial agent at a predetermined rate, said method comprising positioning a sustained release diffusional delivery system at a location in need of such beneficial agent, said sustained release diffusional delivery system comprising:

(a) a reservoir that encloses said beneficial agent, an entirety of said reservoir that encloses said beneficial agent being impermeable and non-porous to fluids external of said reservoir during delivery of the beneficial agent; and

(b) a capillary channel in communication with said reservoir and the exterior of the system for delivering said beneficial agent from the system;

said capillary channel having a cross-sectional area and a length selected to provide said predetermined rate.

26. A method of delivering a beneficial agent formulated in a glassy sugar matrix at a predetermined rate, said method comprising positioning a sustained release delivery system at a location in need of the beneficial agent formulated in a glassy sugar matrix, said sustained release delivery system comprising:

(a) a reservoir comprising said beneficial agent; and

(b) a capillary channel in communication with said reservoir and the exterior of the system for delivering said beneficial agent from the system,

said capillary channel having a cross-sectional area and a length selected to provide said predetermined rate.

30. The method of delivering a beneficial agent according to claim 26, wherein said reservoir encloses said beneficial agent, an entirety of said reservoir that encloses said beneficial agent being impermeable and non-porous to fluids external of said reservoir during delivery of said beneficial agent.

27. A method of preparing a sustained release delivery system for delivering a beneficial agent at a predetermined rate, said method comprising the steps of:

(a) providing a reservoir that encloses the beneficial agent, an entirety of said reservoir that encloses said beneficial agent being impermeable and non-porous to fluids external of said reservoir during delivery of the beneficial agent;

(b) filling said reservoir with the beneficial agent; and

(c) providing the reservoir with a diffusion controller,

said diffusion controller comprising a capillary channel having a cross-sectional area and a length selected to provide said predetermined rate.

28. A method of preparing a sustained release delivery system for delivering a beneficial agent formulated in a glassy sugar matrix at a predetermined rate, said method comprising the steps of:

(a) providing a reservoir;

(b) providing a beneficial agent formulated in a glassy sugar matrix in said reservoir; and

(c) providing the reservoir with a diffusion controller,

said diffusion controller comprising a capillary channel having a cross-sectional area and a length selected to provide said predetermined rate.

31. The method of delivering a beneficial agent according to claim 28, wherein said reservoir encloses said beneficial agent, an entirety of said reservoir that encloses said beneficial agent being impermeable and non-porous to fluids external of said reservoir during delivery of the beneficial agent.