Ocular drug delivery device

• US 4,014,335 A
• Filed: 03/25/1976
• Issued: 03/29/1977
• Est. Priority Date: 04/21/1975
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Arnold, Randall K.
• Primary Examiner(s): Medbery, Aldrich F.
• Application Number:
  US05/670,267
• Time in Patent Office: 369 Days
• Field of Search: 128/172, 128/260, 128/261, 128/268, 128/272, 128/130, 424/19, 424/21, 424/28, 424/22, 424/30
• US Class Current: 424/427
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• 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

An ocular drug dispensing device for administering a drug at a controlled and continuous dosage unit rate to the eye to produce a local or systemic physiological or pharmacological effect is comprised of a shaped body insoluble in tear fluid and comprised of a first wall, a third wall distant from the first wall, a second wall interposed between the first and third wall and extending around their peripheries for sealingly engaging the first and third wall, a reservoir defined by the inner surfaces of the walls and containing the drug or a mixture of the drug in a carrier and wherein at least one of the first and third walls is formed of an imperforate drug release rate controlling material permeable to the passage of drug or a microporous material containing in the micropores a drug release rate controlling medium permeable to the passage of drug for administering a therapeutically effective amount of drug over a prolonged period of time.

Claims

1. An ocular device for the administration of drug comprising a three layered laminate having a pair of separate and discrete first and third walls formed of a material insoluble in tear fluid with one of the walls formed of a drug release rate controlling material permeable to the passage of drug and the other wall formed of a material impermeable to the passage of drug, a second wall interposed between the first and third walls and formed with an inwardly disposed hole with the second wall sealingly engaging the first and third walls to form a reservoir containing a drug selected from the group consisting of antibiotic, antibacterial, antiviral, antiallergenic, anti-inflammatory, miotic, anticholinesterase, mydriatic and sympathomimetic drugs, and wherein drug is administered from the device at a controlled and continuous rate by passage through the rate controlling wall over a prolonged period of time.

2. The ocular device for the administration of drug according to claim 1 wherein the antibiotic is a member selected from the group consisting of tetracycline, chlortetracycline, bacitracin, neomycin, polymyxin, gramicidin, oxytetracycline, chloramphenicol, gentamycin, penicillin, erythomycin, and mixtures thereof.

3. The ocular system for the administration of drug according to claim 1 wherein the antibacterial is a member selected from the group consisting of sulfonamide, sulfacetamide, sulfamethizole, sulfisoxyazole, and mixtures thereof.

4. The ocular system for the administration of drug according to claim 1 wherein the antiviral drug is idoxuridine.

5. The ocular device for the administration of drug according to claim 1 wherein the anti-inflammatory drug is a member selected from the group consisting of hydrocortisone, hydrocortisone acetate, dexamethasone, dexamethasone 21-phosphate, flucoinolone, medrysone, prednisolone, methylprednisolone, prednisolone 21-phosphate, prednisolone acetate, fluoromethalone, betamethasone and triaminolone.

6. The ocular device for the administration of drug according to claim 1 wherein the sympathomimetic is a member selected from the group consisting of phenylephrine, epinephrine and hydroamphetamine.

7. The ocular device for the administration of drug according to claim 1 wherein the drug release rate controlling wall is formed of a homogenous material permeable to the passage of drug by diffusion.

8. The ocular device for the administration of drug according to claim 1 wherein the reservoir containing the drug additionally contains a carrier which carrier is more permeable to the passage of drug than is the drug release rate controlling wall.

9. The ocular device for the administration of drug according to claim 1 wherein the second wall is formed of a member selected from the group consisting of poly(vinylacetate), cross-linked poly(vinyl alcohol), cross-linked poly(vinyl butyrate), ethylene-ethylacrylate copolymer, poly(ethyl hexylacrylate), poly(vinyl chloride), poly(vinyl acetate), ethylene-vinyl acetate copolymer, plasticized ethylene-vinyl acetate copolymer, poly(vinyl ester), poly(vinyl formal), and polyamide.

10. The ocular device for the administration of drug according to claim 1 wherein the drug is mixed with a carrier selected from the group of solid, semi-solid, liquid, gel and colloidal carriers.

11. The ocular device for administering drug according to claim 1 wherein the drug is mixed with a carrier selected from the group consisting of a polysaccharide, agar, agarose, algin, sodium alginate, carrageenan, fucordan, furcellaran, laminaran, hypnea, gum arabic, gum ghatti, gum karaya, starch, gum tragacanth, guar gum, locust bean gum, quince psyllium, okra gum, pectin, dextran, amylose, amylopectin, dextrin, cellulose, methylcellulose, hydroxyalkyl cellulose wherein the alkyl contains 1 to 7 carbon atoms, sodium carboxymethylcellulose, sodium carboxyethylcellulose, ethylcellulose, and mixtures thereof.

12. The ocular device for administering drug according to claim 1 wherein the device has a geometric shape selected from the group consisting of ring, bean, elliptical, banana, rectangular, square, trapezoidal, triangular, half-circle and crescent shaped devices.

13. An ocular device for the administration of an ophthalmic drug comprising a three layered laminate having a pair of separate and discrete first and third walls formed of a material insoluble in tear fluid with one of the walls formed of a drug release rate controlling material permeable to the passage of drug and the other wall formed of a material impermeable to the passage of drug, a second wall interposed between the first and third walls and formed with an inwardly disposed hole with the second wall sealingly engaging the first and third walls to form a reservoir containing a drug selected from the group of ophthalmic drugs consisting of pilocarpine, pilocarpine and its acceptable salts, eserine salicylate, carbachol, eserine, phospholine iodide, demecarium bromide, cyclopentolate, homatropine, scopolamine, atropine, atropine sulfate, eucatropine, and tropicamide.

14. An ocular device for the administration of drug comprising a three layered laminate having a pair of separate and discrete first and third walls formed of a material insoluble in tear fluid with one of the walls formed of a microporous material, the pores of which contain a drug release rate controlling medium permeable to the passage of drug and the other wall formed of a material impermeable to the passage of drug, a second wall positioned between the first and third walls and formed with an inwardly disposed hole with the second wall sealingly engaging the first and third walls to form a reservoir containing a drug selected from the group consisting of antibiotic, antibacterial, antiviral, antiallergenic, anti-inflammatory, miotic, anticholinesterase, mydriatic and sympathomimetic drugs, and wherein drug is administered from the device at a controlled and continuous rate by passage through the rate controlling medium over a prolonged period of time.

15. An ocular device for the administration of drug according to claim 14 wherein the drug is an ophthalmic drug selected from the group consisting of pilocarpine, pilocarpine and its acceptable salts, eserine, eserine salicylate, carbachol, phospholine iodide, demecarium bromide, cyclopentolate, homatropine, scopolamine, atropine, atropine sulfate, eucatropine and tropicamide.

16. An ocular system for the administration of drug according to claim 14 wherein the microporous wall is formed of a microporous material having a porosity of between 5 percent and 95 percent.

17. An ocular delivery device for the continuous administration of drug over a prolonged period of time comprising a sealed container shaped for insertion and placement in the eye, said container comprising a pair of first and third membrane walls spaced from each other, each formed of a material insoluble in ocular fluid with one of the membrane walls formed of a material permeable to the passage of ocular drug and the other membrane wall formed of a material substantially impermeable to the passage of drug, a second peripheral shaped wall interposed between and sealingly engaging the first and third membrane walls along their outer faced peripheries to define an integral unit and form a reservoir defined by the inner surface of the first, second and third walls, said reservoir containing ocular drug selected from the group consisting of locally and systemically acting drugs which are released therefrom at a controlled and continuous rate by passage through the release rate controlling membrane wall over a prolonged period of time.

18. The ocular delivery device for the continuous administration of ocular drug according to claim 17 wherein the second wall is ring, elliptical, oval or annular shaped.

19. The ocular delivery device for the continuous administration of ocular drug according to claim 17 wherein the device is longer than wide and is designed for insertion and placement in the cul-de-sac of the eye.

20. An ocular delivery device for the continuous administration of ocular drug according to claim 17 wherein the drug is a member selected from the group consisting of antibiotic, antibacterial, antiviral, antiallergenic, anti-inflammatory, miotic, anticholinesterase, mydriatic and sympathomimetic drugs.

21. An ocular delivery device for the continuous administration of drug according to claim 17 wherein the drug is a member selected from the group consisting of phenylephrine, epinephrine, pilocarpine, pilocarpine and its acceptable salts, eserine, idoxuridine, tetracycline, neomycin, penicillin, erythromycin, scopolamine, atropine, physostigmine, hydrocortisone, prednisolone, and sulfisoxazole.

22. An ocular delivery device for the continuous administration of drug according to claim 17 wherein the membrane wall is formed of a material permeable to the passage of ocular drug by diffusion selected from the group consisting of ethylene-vinyl acetate copolymer, plasticized ethylene-vinyl acetate copolymer, poly(dimethylsiloxane) and poly(ethylene).

23. An ocular delivery system for the continuous administration of drug according to claim 17 wherein the device is sized, shaped and adapted for insertion and placement into a human eye and has a length of 4 to 20 millimeters, a width of 1 to 15 millimeters and a thickness of 0.1 to 4 millimeters.

24. An ocular delivery device for the continuous administration of drug according to claim 17 wherein the reservoir has a diameter of 1.2 to 14.8 millimeters and contains from 1 microgram to 100 milligrams of ocular drug.

25. An ocular delivery device for the continuous administration of drug comprising a closed container shaped and sized for insertion and placement in the eye, said container comprising a pair of first and third walls spaced from each other, each formed of a material insoluble in ocular fluid with one of the walls formed of a microporous polymeric material capable of housing in its pores a drug release rate controlling medium permeable to the passage of drug and the other wall formed of a material substantially impermeable to the passage of drug, a second peripheral shaped wall positioned between and sealingly engaging the first and third walls along their marginal faced peripheries to define an integral unit and form a reservoir defined by the inner surface of the first, second and third walls, said reservoir containing an ocular drug selected from the group of drugs that give physiologic and pharmacologic beneficial effects, which is released from the device at a controlled and continuous rate by passage through the release rate controlling medium housed in the pores over a prolonged period of time.

26. The ocular delivery device for the continuous administration of drug according to claim 25 wherein the drug has limited solubility in the medium housed in the pores with the drug selected from the group consisting of mydriatic, parasympatholytic, parasympathomimetic, anticholinesterase, adrenergic, anti-inflammatory, anti-infective, antifungal and antiviral drugs.

27. The ocular delivery device for the continuous administration of drug according to claim 25 wherein the medium housed in the micropores is eye fluid.