Active agent dispenser

• US 4,564,364 A
• Filed: 05/26/1983
• Issued: 01/14/1986
• Est. Priority Date: 05/26/1983
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Zaffaroni, Alejandro, Wong, Patrick S. L.
• Primary Examiner(s): Williams, Howard S.
• Application Number:
  US06/498,381
• Time in Patent Office: 964 Days
• Field of Search: 604/896, 604/304, 604/307, 604/308, 604/897
• US Class Current: 424/484
• CPC Class Codes: A61F 2013/0296 for making transdermal patches (chemical processes excluded)
• CPC Class Codes: A61K 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• 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

The release pattern of a dispersion type active agent dispenser can be improved by forming the device from a depleted zone containing the agent at a concentration no greater than the saturation and a non-depleted zone containing the agent dispersed in the matrix at a uniform concentration greater than saturation. The depleted zone is disposed between the surface through which the agent is to be dispensed and at least a substantial portion of the non-depleted zone with the interface therebetween disposed at a non-uniform distance from the releasing surface. Certain embodiments are particularly useful for the transdermal administration of drugs.

Claims

1. A dispenser for releasing an active agent into an environment of use comprising in combination:

(a) at least onr non-depleted zone comprising a matrix material containing said agent at a concentration greater than the saturation concentration of the agent in said matrix material; and

(b) at least one depleted zone comprising a matrix material containing said agent at a concentration no greater than the saturation concentration of the agent in the matrix material, said depleted zone being disposed between a surface through which the agent is to be released to the environment and at least a substantial portion of said non-depleted zone with the interface between said depleted and non-depleted zones being disposed at a nonuniform distance from said releasing surface.

2. The dispenser of claim 1 wherein said interface is disposed in a plane oblique to said releasing surface.

3. The dispenser of claim 1 wherein the non-depleted zone is disposed between two depleted zones and said agent is released to the environment through two releasing surfaces.

4. The dispenser of claim 1 wherein:

(a) said non depleted zone is in the form of a body having at least one recess extending inwardly in a convergent manner from the surface of said non depleted zone proximate the agent releasing surface of said dispenser, and

(b) said depleted zone is disposed within said recess.

5. The dispenser of claim 4 further comprising an agent impermeable barrier disposed on the exterior of said dispenser other than the surface through which said agent is released.

6. The dispenser of claim 4 wherein said dispenser has a cylindrical exterior and said recess is conical.

7. The dispenser of claim 6 wherein said recesses comprise a plurality of grooves.

8. The dispenser of claim 6 wherein said recess comprises a plurality of indentations.

9. The dispenser of claim 4 wherein said releasing surface is the surface of said body proximate said depleted zone.

10. The dispenser of claim 4 wherein said non-depleted zone is a planar structure provided with a plurality of said recesses.

11. The dispenser of claim 1 wherein the matrix material of said depleted and non-depleted zone is the same.

12. The dispenser of claim 1 adapted to release active agent primarily through only one surface wherein said releasing surface comprises the face of said dispenser most proximate said depleted zone.

13. The dispenser of claim 12 for dispensing agent to the skin further comprising means for maintaining said releasing surface in agent transferring relationship to the skin.

14. The dispenser of claim 13 wherein said means for maintaining said releasing surface in agent trasferring relationship to the skin comprises an adhesive property of said depleted zone.

15. The dispenser of claim 13 wherein said means for maintaining said releasing surface in agent transferring relationship to the skin comprises an agent permeable conact adhesive on said releasing surface.

16. The dispenser of claim 13 further comprising an agent impermeable coating on the surface of the dispenser opposite said releasing surface.

17. The dispenser of claim 1 further comprising means for restricting said releasing surface to a predetermined portion of the exterior surface of said dispenser proximate said depleted zone.

18. The dispenser of claim 17 wherein said restricting means comprises at least in part, an agent impermeable barrier disposed on at least a portion of the exterior of said dispenser other than said releasing surface.

19. The dispenser of claim 17 wherein said restricting means comprises, at least in part, the configuration of the dispenser wherein the exposed surface area other than the releasing surface is insubstantial compared to the area of the releasing surface.

20. A dispenser for releasing an active agent into an environment of use comprising, in combination:

(a) at least one non-depleted zone comprising a matrix material containing said agent at a substantially uniform concentration greater than the saturation concentration of said agent in said matrix material;

(b) at least one depleted zone comprising a matrix material containing said agent at a concentration no greater than the saturation concentration of said agent in said matrix, said depleted zone being disposed between the surface through which said agent is released to the environment and at least a substantial portion of said non-depleted zone, said depleted and non-depleted zones being configured such that the average concentration of said agent in said dispenser increases with the distance from the releasing surface while the actual concentration of said agent in the non-depleted zone remains constant.

21. A method for manufacturing an active agent dispenser for releasing said agent to an environment of use through at least one releasing surface, said dispensing comprising an agent depleted zone and an agent non-depleted zone said agent depleted zone being disposed proximate said releasing surface;

which method comprises;

(a) forming a dispersion of said active agent in a matrix material at a substantially constant concentration greater than the saturation concentration of said agent in said matrix;

(b) forming an agent depleted matrix material which contains said agent at a concentration no greater than the saturation concentration of said agent in said matrix material;

(c) bonding said non-depleted zone to said depleted zone to form a body having said depleted zone disposed proximate said releasing surface, and

(d) configuring said depleted and non-depleted zones such that the average concentration of said agent in said dispenser increases with the distance from the releasing surface over a substantial portion of the thickness of the dispenser.

22. The method of claim 21 further comprising the step of bonding an agent impermeable coating onto the surface of said body opposite the releasing surface.

23. The method of claim 21 wherein said body is formed by coextrusion of the depleted and non-depleted zones.

24. The method of claim 21 wherein said body is formed by casting one of said depleted and depleted zones onto the other.