Novel drug delivery device

• US 3,948,262 A
• Filed: 03/10/1975
• Issued: 04/06/1976
• Est. Priority Date: 04/01/1969
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Zaffaroni, Alejandro
• Primary Examiner(s): Medbery, Aldrich F.
• Application Number:
  US05/556,546
• Time in Patent Office: 393 Days
• Field of Search: 128/260, 128/263, 128/268, 128/270, 128/272, 128/285, 128/284, 128/130
• US Class Current: 128/833
• CPC Class Codes: A61F 6/144 with T-configuration
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• 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 9/0036 Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
• CPC Class Codes: A61K 9/0039 Devices retained in the uterus for a prolonged period, e.g. intrauterine devices for contraception
• CPC Class Codes: A61K 9/0092 Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
• CPC Class Codes: A61L 15/58 Adhesives
• 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 drug delivery device for administering a drug at a controlled rate for a prolonged period of time to produce a local or systemic physiological or pharmacological effect is comprised of a wall surrounding a reservoir containing a drug. The reservoir is formed of a drug carrier permeable to the passage of the drug and in which the drug has limited solubility. The wall is formed in at least a part of a drug release rate controlling material also permeable to the passage of the drug, but the rate of passage of the drug through the wall is lower than the rate passage of the drug through the drug carrier so that drug release by the wall is the drug release rate controlling step for releasing drug from the drug delivery device.

Claims

1. A delivery device for the controlled and continuous administration of drug to a body site environment over a prolonged period of time, said device comprising:

a. a means for containing and releasing the drug at a controlled rate comprising a reservoir containing a dissolved drug portion and an undissolved replacement drug portion in a liquid carrier material permeable to the passage of the drug therethrough, said drug having limited solubility in said liquid;

the replacement drug portion being present in an amount in excess of its solubility in the carrier material and in an amount sufficient to maintain the amount of the dissolved drug portion substantially constant during said prolonged period of time, said means further comprising;

b. a shaped wall that surrounds the reservoir and is characterized by being insoluble in body fluid, maintaining its integrity during said prolonged period of time, and by being formed at least in part of a substantially homogeneous drug release rate controlling material permeable to the passage of the drug but having a lower permeability to the drug than the permeability of the liquid carrier material to the drug;

c. so that the device when placed at the body site, continuously releases drug from the reservoir to the body site at a physiologically or pharmacologically effective controlled rate by metered passage through the wall, the dissolved drug so released being replaced by the continuous dissolving of replacement drug in the carrier material so as to substantially maintain the amount of dissolved drug in the reservoir substantially constant during said prolonged period of time.

2. A delivery device in accordance with claim 1 wherein the drug release rate controlling material is a natural or synthetic organic polymer free from silicon atoms in the polymeric network.

3. A delivery device in accordance with claim 1 wherein the wall is permeable to the passage of drug by diffusion.

4. A delivery device in accordance with claim 3 wherein the cumulative amount of dissolved drug and undissolved drug contained in the liquid carrier material is in an amount to provide a complete dosage regimen for a living organism for a period of time in an amount of at least one month.

5. A delivery device in accordance with claim 1 wherein the drug release rate controlling material is ethylene-vinyl acetate copolymer.

6. A delivery device in accordance with claim 1 wherein the permeability of the liquid carrier material to drug is from 2 to 100 times the permeability of the drug release rate controlling material to drug.

7. A delivery device in accordance with claim 1 wherein the rate of controlled and continuous release from the device is substantially independent of time.

8. A delivery device in accordance with claim 1 wherein drug in the reservoir is maintained at the same thermodynamic activity until substantially all of the drug has been transferred from the reservoir to the exterior of the device.

9. A delivery device in accordance with claim 1 wherein the drug is soluble in the liquid carrier material in an amount of one part of drug to about 10 to 15,000 parts of liquid carrier material at 25°

C.

10. A delivery device in accordance with claim 1 wherein liquid carrier material is permeable to the passage of drug by diffusion.

11. A delivery device in accordance with claim 1 wherein the prolonged period of time is at least a period of 1 month.

12. A delivery device in accordance with claim 1 wherein the device is an intrauterine device, said environment of use being the uterus of a female mammal.

13. A delivery device in accordance with claim 12 wherein the drug is comprised of progesterone, the liquid carrier material is an oil, and the drug release rate controlling medium material is ethylene-vinyl acetate copolymer.

14. A delivery device in accordance with claim 1 wherein the permeability of said drug release rate controlling material to said drug is such that the rate of flow of drug from the reservoir is less than the rate of clearance of migrated drug from the external surface of the device when the device is in contact with body tissues or fluids.

15. A delivery device in accordance with claim 1 wherein the drug is soluble in the liquid carrier material in an amount of one part of drug to 100 to 1000 parts of liquid carrier material at 25°

C.

16. A delivery device in accordance with claim 13 wherein the prolonged period of time is one to three years and the total amount of progesterone present in said reservoir is sufficient to administer from 10 to 200 μ

g per day during said period.

17. A delivery device in accordance with claim 1 wherein the materials comprising the reservoir and the wall are such that said release and dissolving occurs without substantial absorption of fluid from the environment into the device.

18. A delivery device in accordance with claim 1 wherein the drug release rate controlling material is substantially impermeable to fluids of said environment.

19. A delivery device in accordance with claim 16 wherein the materials comprising the reservoir and the wall are such that said release and dissolving occurs without substantial absorption of body fluids.

20. A delivery device in accordance with claim 16 wherein the drug release rate controlling material is substantially impermeable to body fluids.