Microporous drug delivery device

• US 3,993,072 A
• Filed: 10/17/1975
• Issued: 11/23/1976
• Est. Priority Date: 08/28/1974
• 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:
  US05/623,427
• Time in Patent Office: 403 Days
• Field of Search: 128/260, 128/268, 128/130, 128/270, 128/2 R, 128/263, 424/16, 424/19, 424/20, 424/22
• US Class Current: 424/430
• CPC Class Codes: A61F 6/14 intra-uterine type
• 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 a pore size of 10 angstroms to 100 microns and formed 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 dissolved drug by diffusion, (c) a medium made of a pharmaceutically acceptable release rate controlling material housed in the micropores, said drug having a solubility of 1 part drug in 10 to 15,000 parts of medium with the medium permeable to the passage of drug by diffusion but at a lower rate than through the carrier, and (d) wherein drug is metered at a controlled and continuous rate from the device by passage from the carrier and through the medium with release by the medium being the rate controlling step for releasing drug over a prolonged period of time from the device to produce the desired results.

2. The drug delivery device for the continuous administration of a drug at a controlled rate according to claim 1 wherein the microporous material is a member selected from the group of microporous polymers consisting of linear polyesters of carbonic acid, poly(vinylchloride), polyamides, styrene-acrylic acid copolymers, polysulfones, halogenated poly(vinylidene), polychloroethers, poly(urethanes) and poly(imides).

3. The drug delivery device for the continuous administration of a drug at a controlled rate according to claim 1 wherein the release rate controlling medium housed in the micropores is a member selected from the group consisting of water, silicon oil, caster oil, olive oil, mixed oils, emulsions of castor oil in non-aqueous solutions of pigskin gelatin, condensation products of castor oil and ethylene oxide combining about 30 to 35 moles of ethylene oxide per mole of castor oil, polymeric sodium alginate and emulsified gum tragacanth.

4. 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 a pore size of 10 angstroms to 100 microns and formed with tortuous 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 a pharmaceutically acceptable release rate controlling material housed in the micropores with the medium permeable to the passgage of drug by diffusion but at a lower rate than through the carrier which rate is given by the equation ##EQU8## wherein J is the flux in gm/cm² sec, ε

is the porosity in cm³ /cm³, T is the tortuosity factor, D is the diffusion coefficient in cm² /sec and dc/dx is the drug concentration gradient across the wall, and (d) wherein drug is metered at a controlled and continuous rate from the device by passage from the carrier and through the medium with release by the medium being the rate controlling step for releasing drug over a prolonged period of time from the device to produce the desired result.

5. The drug delivery device for the continuous administration of a drug at a controlled and continuous rate according to claim 4 wherein the reservoir contains a drug selected from the group consisting of aspirin, salicylamide, atropine, scopolamine, methscopolamine, oxphenonium and papaverine.

6. 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 a pore size of 10 angstroms to 100 microns formed with paths through the wall and selected from the group consisting of isotropic and anisotropic microporous materials, (b) a reservoir surrounded by the wall comprising a drug and a drug carrier selected from the group consisting of inorganic and organic materials permeable to the passage of drug by diffusion, (c) a medium formed of a release rate controlling material housed in the micropores and permeable to the passage of drug by diffusion, and (d) wherein drug is metered from the device at a controlled and continuous rate by passage through the carrier and medium with release by the medium being the rate controlling step for releasing drug over a prolonged period of time to produce the desired result.

7. A drug delivery device for the continuous administration of a drug at a controlled rate to produce a beneficial result according to claim 6 wherein the micropores ae filled with a liquid release rate controlling medium present in the environment of use.

8. A drug delivery device for the continuous administration of a drug at a controlled rate to produce a beneficial result according to claim 6 wherein a diffusive medium is added to the micropores before the device is placed in the environment of use.

9. A drug delivery device for the continuous administration of a drug at a controlled rate to produce a beneficial result according to claim 6 wherein the wall forming material is a member selected from the group consisting of anisotropic microporous materials formed of ionically associated polyelectrolytes and microporous polymers formed by the co-precipitation of a polycation and a polyanion.

10. A drug delivery device for the continuous administration of a drug at a controlled rate to produce a beneficial result according to claim 6 wherein the reservoir contains a drug selected from the group consisting of phenelzine, imipramine, tranylcypromine, pargylene, chloropromazine, promazine, fluphenazine, reserpine, deserpidine, meprobamate, chlordiazepoxide and epinephrine.

11. 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 essentially nontoxic material having a plurality of micropores with continuous paths and selected from the group consisting of isotropic and anisotropic microporous materials, (b) a reservoir surrounded by the wall and containing a solid carrier permeable to an agent, (c) an agent selected from the group consisting of insulin, protamine zinc insulin, globin zinc insulin and isophane zinc insulin present in the carrier in an amount sufficient for the device to meter agent therefrom, (d) a liquid release rate controlling material permeable to the passage of agent by diffusion present in the micropores, and (e) 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 with release by the liquid being the release rate controlling step for releasing agent over a prolonged period of time to produce a useful physiological result.

12. 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 material selected from the group consisting of isotropic and anisotropic microporous materials, (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 carrier to furnish it at a continuous and controlled rate according to Fick'"'"'s Law of Diffusion to (c) a liquid medium permeable to the passage of drug by diffusion charged in the micropores with the rate of passage of drug through the medium lower than the rate of passage of drug through the carrier, and (d) wherein the device releases drug when in a nasal environment by passage through the carrier and through the medium with release by the medium being the rate controlling step for releasing drug over a prolonged period of time to produce a useful result.

13. The nasal delivery device for dispensing a drug within a nasal passage at a controlled rate according to claim 12 wherein the radius of the micropores is at least 10 times larger than the molecular radius of the nasal drug molecule.

14. The nasal delivery device for dispensing a drug within a nasal passage at a controlled rate according to claim 12 wherein the drug is amyl nitrite.

15. A vaginal delivery device for continuously administering a vaginally acceptable drug at a controlled rate, wherein the device is comprised of (a) a wall defining the device dimensioned for insertion and retention within the vaginal cavity, with the wall formed of a vaginally acceptable material selected from the group consisting of isotroic and anisotropic microporous polymeric materials having pores for the 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 and containing a drug selected from the group consisting of estrogenic and progestational steroids in an amount sufficient to administer drug from the carrier over a prolonged period of time to, (c) a liquid release rate controlling medium permeable to the passage of drug in said pores, and (d) wherein the device releases drug when in the environment of use by passage from the reservoir and through the medium with release by the medium rate controlling step for releasing drug to the environment to produce a local or systemic beneficial result over a prolonged period of time.

16. The vaginal drug delivery device for continuously administering a vaginally acceptable drug at a controlled rate according to claim 15 wherein the drug is a member selected from the group consisting of 17β

-estradiol, ethynyl estradiol, progesterone, 17α

-hydroxyprogesterone acetate, 19-nor-progesterone and norethindone.

17. The vaginal drug delivery device for continuously administering a vaginally acceptable drug at a controlled rate according to claim 15 wherein the carrier is a member selected from the group consisting of gelatin, starch, carbohydrate, Irish moss and hydrophilic hydrogels of esters of acrylic acids.

18. A sublingual delivery device for the continuous administration of a pharmaceutically acceptable drug at a controlled rate, wherein the device is comprised of (a) a wall defining the device and adapted for drug release to a sublingual substrate with said wall fomed 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 drug with the carrier containing a member selected from the group consisting of nitroglycerin and mannitol nitrate in an amount sufficient to administer same from the device at a continuous and controlled rate for a prolonged period of time, (c) a release rate controlling medium permeable to the passage of said drug in the micropores, and (d) wherein the sublingual devices administered drug when in the environment of use by passage from the reservoir and through the medium with release by the medium being the rate controlling step for releasing drug to yield a useful result.

19. An oral delivery device for continuously administering an orally acceptable beneficial drug, wherein said device is comprised of (a) a wall defining the oral device and formed of a pharmaceutically acceptable microporous material, (b) a reservoir surrounded by the wall and comprising a solid carrier having a high diffusivity for a drug and permeable to the passage of an oral diffusible drug, (c) a drug in the reservoir selected from the group consisting of bephenium hydroxynaphoate, dapsone, uracil mustard, thioquanine and procarbazine, (d) a medium permeable to the passage of drug present in the micropores but at a lower rate than through the carrier, and (e) wherein the device when in the environment of use releases drug by passage from the reservoir and through the medium with release by the medium rate controlling for releasing drug over a prolonged period of time.