Novel drug delivery device

• US 3,948,254 A
• Filed: 08/28/1974
• Issued: 04/06/1976
• Est. Priority Date: 11/08/1971
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Zaffaroni, Alejandro
• Primary Examiner(s): Trapp, Lawrence W.
• Application Number:
  US05/501,207
• Time in Patent Office: 587 Days
• Field of Search: 128/270-272, 128/127-130, 128/260, 3/1, 424/22
• US Class Current: 128/833
• 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 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 solid drug carrier permeable to the passage of the drug. The wall is formed in at least a part of a microporous material the pores of which contain a drug release rate controlling medium also permeable to the passage of the drug, but the rate of passage of the drug through the medium is lower than the rate passage of the drug through the solid drug carrier so that drug release by the medium in the microporous wall is the drug release rate controlling step for releasing drug from the drug delivery device.

Claims

1. A drug delivery device for the continuous administration of a drug at a controlled rate to produce a beneficial result, said device comprising (a) a wall formed of a microporous material having a plurality of micropores with diffusional conduits through the wall, (b) a reservoir surrounded by the wall comprising a solid carrier containing dissolved and undissolved drug with the carrier permeable to the passage of the dissolved drug by diffusion, (c) a medium made of pharmaceutically acceptable release rate controlling material housed in the micropores with the medium permeable to the passage of drug by diffusion, and (d) wherein drug is metered at a controlled and continuous rate from the device by passage from the solid and through the medium for a prolonged period of time to produce the desired results.

2. The drug delivery device for the continuous administration of drug according to claim 1 wherein the rate of passage of drug through the medium is lower than the rate of passage of drug through the carrier so that release by the medium is release rate controlling for releasing drug from the device.

3. An intrauterine delivery device for continuously administering a uterine acceptable antifertility agent at a controlled rate, wherein the device is comprised of (a) a wall dimensioned for insertion and retention within the uterine cavity, the wall formed of a microporous material insoluble in uterine fluid and capable of maintaining its physical structure during its uterine use, and having a plurality of micropores with diffusional paths through the wall, (b) a reservoir surrounded by the wall, comprising a solid carrier containing dissolved and undissolved diffusible antifertility agent, said carrier permeable to the passage of agent and containing undissolved agent in an amount sufficient to replace dissolved agent in the carrier in an amount essentially equal to the amount of dissolved agent released from the device at a continuous and controlled rate for a prolonged period of time, (c) a liquid release rate controlling material housed in the micropores with the liquid permeable to agent by diffusion and nontoxic to the uterine environment, and (d) wherein agent is released from the device when positioned in the uterus by passage of agent from the carrier and through the liquid to yield the desired result.

4. The intrauterine device for continuously administering an agent according to claim 3 wherein the rate of passage of agent through the medium is lower than the rate of passage of agent through the carrier so that release by the medium is release rate controlling for releasing agent from the device.

5. An intrauterine device adapted for easy insertion and prolonged retention in a fertile uterus, the device consisting of a transverse wall formed of a microporous material having a plurality of pores with diffusional paths through said wall, a longitudinal wall dependent from the transverse wall and suitably united therewith, said longitudinal wall formed of a microporous material and having a plurality of pores with diffusional paths through said wall, a reservoir surrounded by the transverse or longitudinal wall, said reservoir comprising a solid carrier containing diffusible antifertility agent with the carrier permeable to the passage of agent by diffusion, a liquid release rate controlling material housed in said micropores, with the liquid permeable to agent by diffusion, and wherein the device releases agent when positioned in the uterus by passage of agent from the carrier and through the liquid to yield the desired result.

6. The intrauterine device adapted for easy insertion and prolonged retention according to claim 5 wherein the rate of passage of agent through the medium is lower than the rate of passage of agent through the carrier so that release by the medium is release rate controlling for releasing agent from the intrauterine device.

7. An artificial gland for dispensing a pharmaceutically acceptable agent having a physiological function essentially equivalent to a natural gland, wherein said gland is comprised of (a) a wall defining the gland and dimensionally adapted for insertion and placement within a biological environment to dispense said agent with the wall formed of an essentially nontoxic microporous material having a plurality of micropores with continuous diffusional paths, (b) a reservoir surrounded by the wall and containing a solid carrier permeable to an agent, (c) an agent present in the carrier in an amount sufficient for the device to meter agent therefrom at a continuous and controlled rate for a prolonged period of time (d) a liquid agent release rate controlling material permeable to the passage of agent by diffusion present in the micropores, (e) and wherein the gland releases agent in the environment of use by passage of agent from the carrier and through the liquid to the exterior of the gland to produce a useful physiological result.

8. The artificial gland for dispensing agent according to claim 7 wherein the rate of passage of agent through the medium is lower than the rate of passage of agent through the carrier so that release by the medium is release rate controlling for releasing agent from the gland.

9. A nasal delivery device for dispensing a drug within a nasal passage at a controlled rate wherein the nasal device is comprised of (a) a wall defining the device dimensioned for insertion and placement within a nasal passage, with the wall formed of a nasal acceptable microporous material, (b) a reservoir surrounded by the wall and comprised of a solid carrier permeable to drug and containing drug in an amount sufficient for the device to meter it at a continuous and controlled rate for a prolonged period of time from the device, (c) a liquid medium permeable to the passage of drug by diffusion charged in the micropores, and (d) wherein the device releases drug when in a nasal environment by passage of drug from the carrier and through the liquid to the exterior of the device to produce a useful result.

10. The nasal device for dispensing drug according to claim 9 wherein the rate of passage of agent through the medium is lower than the rate of passage of agent through the carrier so that release by the medium is release rate controlling for releasing drug from the nasal device.

11. An anal delivery device for continuously dispensing a drug within the anal canal at a controlled rate, wherein the device is comprised of (a) a body dimensioned for insertion within the anal canal, said body formed of a wall of microporous material having paths therethrough, (b) a reservoir in the body and surrounded by the wall, said reservoir containing a solid carrier and drug (c) a liquid drug release rate controlling material permeable to the passage of drug by diffusion in the micropores, and (d) wherein the device releases drug in the environment of use by passage of drug from the said device to the environment to produce a useful result.

12. The anal device for dispensing drug according to claim 11 wherein the rate of passage of drug through the liquid material is lower than the rate of passage of agent through the carrier so that release by the material is release rate controlling for releasing drug from the anal device.

13. A device for continuously administering a drug within the ear at a controlled rate, said device comprising (a) a body having a length in excess of its width and dimensioned for insertion within the ear, said body formed of a wall of microporous material and having drug release means, (b) a reservoir surrounded by the wall and consisting of a solid carrier charged with diffusible drug with the carrier permeable to drug, (c) a liquid release rate controlling material permeable to the passage of drug by diffusion in the micropores and (d) wherein the device when in the environment of use releases drug for a prolonged period of time.

14. The ear device for dispensing drug according to claim 13 wherein the rate of passage of drug through the liquid material is lower than the rate of passage of drug through the carrier so that release by the material is release rate controlling for releasing drug from the ear device.

15. A vaginal drug delivery device for continuously administering a vaginally acceptable drug at a controlled rate, wherein the device is comprised of (a) a wall defining the vagainal device dimensioned for insertion and retention within the vaginal cavity, with the wall formed of a vaginally acceptable microporous polymeric material having pores for movement of drug therethrough, (b) a reservoir formed by the inner surface of the wall and surrounded thereby, said reservoir comprised of a solid carrier permeable to the passage of diffusible drug with said reservoir containing drug in an amount sufficient to administer drug from the device at a continuous and controlled rate over a prolonged period of time, (c) a liquid release rate controlling material permeable to the passage of drug in said pore, and (d) wherein the device releases drug when positioned in the environment by passage of drug from the reservoir through the pores to the environment to produce a local or systemic beneficial result.

16. The vaginal drug delivery device for dispensing drug according to claim 15 wherein the rate of passage of drug through the liquid material is lower than the rate of passage of drug through the carrier so that release by the material is release rate controlling for releasing drug from the vaginal device.

17. A vaginal device according to claim 15 wherein the device is ring-shaped.

18. A buccal delivery device for continuously administering a buccally administrable pharmaceutically accpetable drug at a controlled rate, wherein the device is comprised of (a) a wall defining the device and adapted for drug release to a buccal substrate with said wall formed of a pharmaceutically acceptable microporous material, (b) a closed reservoir formed by the inner surface of the wall, said reservoir containing a solid carrier permeable to the passage of diffusible drug with carrier containing the drug in an amount sufficient to administer same from the device at a continuous and controlled rate for a prolonged period of time, (c) a liquid release rate controlling medium permeable to the passage of drug in the micropores, and (d) wherein the buccal drug is released from the device to the substrate by passage of the diffusible drug from the carrier and through the liquid medium in the micropores to yield a useful drug result.

19. The buccal delivery device for administering drug according to claim 18 wherein the rate of passage of drug through the medium is lower than the rate of passage of drug through the carrier so that release by the medium is release rate controlling for releasing drug from the buccal device.

20. A topical device for continuously administering a topically administrable drug at a controlled rate, wherein the device is comprised of (a) a wall defining a topical device and having a configuration corresponding to a biological topical substrate for administering drug thereto, with the wall formed of a pharmaceutically acceptable microporous polymeric material, (b) a reservoir surrounded by the wall and comprised of a solid drug carrier permeable to the passage of drug, (c) a liquid drug release rate controlling diffusion medium permeable to the passage of topically administrable drug in the micropores of said wall, and (d) wherein the drug is released from the device to the topical substrate at a continuous and controlled rate by passage of diffusible drug through the carrier and liquid from the device to produce a beneficial drug effect.

21. The topical device for administering drug according to claim 20 wherein the rate of passage of drug through the medium is lower than the rate of passage of drug through the carrier so that release by the medium is release rate controlling for releasing drug from the topical device.

22. An oral delivery device for continuously administering an orally acceptalbe beneficial drug, wherein said device is comprised of (a) a wall defining the oral device and formed of a pharmaceutically acceptable microporous material for releasing drug, (b) a reservoir surrounded by the wall and comprising a fixed, solid drug carrier having high diffusivity for drug, containing drug and permeable to the passage of oral, diffusible drug, (c) a liquid medium permeable to the passage of drug present in the micropores of the wall, and (d) wherein the drug is released from the device in the environment of use at a continuous and controlled rate by passage of drug from the device for a prolonged period of time.

23. The oral delivery device for administering drug according to claim 22 wherein the rate of passage of drug through the medium is lower than the rate of passage of drug through the carrier so that release by the medium is release rate controlling for releasing drug from the oral device.

24. An implant device for use in a biological environment for continuously adminsitering a beneficial implant releasable agent at a controlled rate, said implant comprising (a) a wall dimensioned for insertion and retention as a depot in a biological environment, with the wall formed of a biologically acceptable microporous material, insoluble in biological fluids and able to maintain its physical integrity during the agent release period, (b) a liquid release rate controlling medium permeable to the passage of agent housed in the micropores of the wall and maintained therein druing period of agent release from the implant, (c) a reservoir surrounded by the wall comprising a solid drug carrier, said carrier having high diffusivity for agent and containing dissolved and undissolved agent with the undissolved agent present in an amount sufficient to supply the wall with an amount essentially equivalent to the amount released by the implant over a prolonged period of time and (d) wherein when the implant is placed in the environment, diffusible agent is metered in an effective amount from the device to the environment to produce a local or systemic effect with the agent released at a controlled and continuous rate by passage through the carrier and medium over said prolonged period of time.

25. The implant device for administering agent according to claim 24 wherein the rate of passage of agent through the medium is lower than the rate of passage of agent through the carrier so that release by the medium is release rate controlling for releasing agent from the implant.

26. An intrauterine device for the administration of an antifertility agent at a controlled and continuous rate over a prolonged period of time, said device comprising, (a) a reservoir comprising both dissolved antifertility agent and undissolved replacement antifertility agent in a solid carrier permeable to the passage of the agent, said undissolved replacement antifertility agent in the solid carrier in an excess amount to continuously replenish and maintain dissolved antifertility agent substantially at its original amount in the solid carrier during the prolonged period of time, said reservoir surrounded by (b) a wall of a configuration which is substantially in the shape of a T, the wall made of a material insoluble in body fluid, and formed of a microporous material containing a diffusive medium permeable to the passage of the antifertility agent, with the permeability of the medium lower than the permeability of the carrier to the agent, (c) and wherein the device when placed in the uterus releases dissolved antifertility agent from the reservoir in an effective amount for contraception by metered passage through the release rate controlling medium, with released agent continuously replaced in the solid core by replacement agent simultaneously dissolving to substantially maintain the amount of dissolved agent in the solid carrier for release at a controlled and continuous rate over a prolonged period of time.

27. The intrauterine device for the administration of agent according to claim 26 wherein the rate of passage of agent through the medium is lower than the rate of passage of agent through the carrier so that release by the medium is release rate controlling for releasing agent from the device.

28. An intrauterine contraceptive device for administering a member selected from the group of antifertility agents consisting of progestational, estrogenic and mixtures thereof at a controlled and constant rate over a prolonged period of time up to three years comprising (a) a wall formed of a microporous material, the material insoluble in body fluid, and capable of substantially maintaining the device'"'"'s shape throughout the prolonged period of time, said wall surrounding (b) a reservoir defined by the wall'"'"'s inner surface with the reservoir comprising a solid carrier containing up to 4,000 milligrams of both dissolved and undissolved replacement agent, with the carrier permeable to the passage of the agent, with the undissolved replacement agent in the carrier present in an excess amount to continuously replenish and maintain a substantially constant supply of dissolved agent in the carrier during the prolonged period of time, (c) a medium present in the micropores and permeable to the passage of agent, with the permeability of the medium lower than the permeability of the carrier to the agent, (d) and wherein agent is administered from the device by releasing dissolved agent with such released agent replaced by undissolved agent to continuously maintain dissolved agent in the solid carrier for supplying it at substantially the same rate to the medium so that agent is metered at a controlled and substantially constant rate from the reservoir by passage through the medium over a prolonged period of time.

29. The intrauterine device for administering an agent according to claim 28 wherein the rate of passage of agent through the medium is lower than the rate of passage of agent through the carrier so that release by the medium is release rate controlling for releasing agent from the device.

30. A method for interfering with the reproductive process, wherein the method is comprised of continuously administering a contraceptive agent from an intrauterine device when placed in a uterine cavity, by the steps of:

(a) inserting into the uterine cavity a device comprising a reservoir containing dissolved and undissolved replacement agent in a solid conductor permeable to the passage of the agent, the undissolved agent present in an amount in excess of its solubility in the conductor and in sufficient amount to maintain the dissolved agent during the prolonged period substantially equal to the amount of dissolved agent originally present in the conductor, the reservoir confined within an enveloping shaped wall made of a biologically acceptable material, insoluble in mammalian body fluid, and formed of a microporous material with the micropores charged with a diffusion liquid medium permeable to the passage of agent, (b) releasing said agent from said reservoir at a controlled, continuous, contraceptively effective rate by diffusional passage through said medium, and (c) continuously replacing the dissolved agent released from the reservoir by continuously dissolving replacement agent in the carrier to substantially maintain the amount of dissolved agent in the solid carrier at its original amount.

31. The method according to claim 30 wherein the rate of passage of agent through the medium is lower than the rate of passage of agent through the conductor so that release by the medium is release rate controlling for releasing agent from the device.

32. An intrauterine delivery device for the controlled and continuous administration of a uterine acceptable antifertility agent wherein the device is comprised of (a) a wall shaped and dimensioned for insertion and placement within the uterine cavity, the wall formed of a uterine acceptable microporous polymeric material insoluble in uterine fluid and capable of maintaining its physical integrity during its uterine use, and having micropores, (b) a reservoir surrounded by the wall, comprising a solid carrier containing dissolved and undissolved diffusible antifertility agent, said carrier permeable to the passage of agent and containing undissolved agent in an amount sufficient to replace dissolved agent in the carrier in an amount essentially equal to the amount of dissolved agent released from the device at a controlled and continuous rate for a prolonged period of time, and (c) wherein agent is released from the device when positioned in the uterus by passage of agent from the carrier and through the micropores to yield the desired result.

33. The intrauterine device according to claim 32 wherein the micropores are filled with a liquid release rate controlling medium in the environment of use.

34. The intrauterine device according to claim 32 wherein a diffusive medium is added to the micropores before the device is placed in the environment of use.