Bioerodible drug delivery device

• US 3,867,519 A
• Filed: 04/27/1972
• Issued: 02/18/1975
• Est. Priority Date: 04/27/1972
• Status: Expired due to Term

• Current Assignee: Alan S. Michaels
• Original Assignee: Alan S. Michaels
• Inventors: Michaels, Alan S.
• Primary Examiner(s): Rose, Shep K.
• Application Number:
  US05/248,168
• Time in Patent Office: 1,027 Days
• Field of Search: 128/260 424/19-22
• US Class Current: 424/473
• 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

Abstract

A drug delivery device for the continuous and controlled administration of a predetermined therapeutically effective dosage of drug to a mamallian patient over a prolonged period of time. The device meters the flow of drug by means of a drug release rate controlling material comprised of an anionic polyvalent metal cation cross-linked polyelectrolyte. The device bioerodes in the biological environment of the patient concurrently with the dispensing or at a point in time after the dispensing of the therapeutically desired amount of drug.

Claims

1. AN OCULAR DELIVERY DEVICE FOR THE SUSTAINED ADMINISTRATION OF A PREDETERMINED DOSAGE REGIMENT OF OPHTHALMIC DRUG TO THE EYE OF A MAMMALIAN PATIENT COMPRISING (1) AN INNER RESERVOIR COMPRISED OF A BIODEGRADABLE MATERIAL CONTAINING A DRUG FORMULATION FOR THE EYE CONFINED THEREIN AND PERMEABLE TO THE PASSAGE OF DRUG, AND (2) AN OUTER MEMBRANE SURROUNDING THE INNER RESERVOIR, THE MEMBRANE PERMEABLE TO THE PASSAGE OF DRUG, BUT AT A LOWER RATE THAN THROUGH THE INNER RESERVOIR, THE MEMBRANE DORMED FROM DRUG RELEASE RATE CONTROLLING BIOERODIBLE MATERIAL COMPRISING A POLYVALENT ION CROSS-LINKED ANIONIC POLYELECTROLYTE WITH THE POLYVALENT ION A MEMBER SELECTED FROM THE GROUP CONSISTING OF ALUMINUM, BARIUM, CADMIUM, CALCIUM COPPER, IRON AND ZINC AND THE ANIONIC POLYELECTROLYTE, A MEMBER SELECTED FROM THE GROUP CONSISTING OF PHARMACEUTICALLY ACCEPTABLE AGAR, ALGIN, ALGINIC ACID, CARRAGEENAN, CELLULOSE, GUM ARABIC, GUM GHATTI, PECTIC ACID, PECTIN, PECTINIC ACID, AND POLYSACCHARIDE, WITH THE POLYELECTROLYTE CROSS-LINKED FROM TWO-TENTHS TO THREE EQUIVALENTS CROSS-LINKING AGENT SELECTED SOLELY FROM SAID POLYVALENT CATION FOR EACH EQUIVALENT OF POLYELECTROLYTE, WHICH MATERIALS BIOERODES IN THE EYE OF THE PATIENT IN FROM FOUR HOURS TO THIRTY DAYS INTO, INNOCUOUS PRODUCTS IN RESPONSE TO THE BIOLOGICAL ENVIRONMENT THEREIN BY A PROCESS OF POLYVALENT ION DISPLACEMENT WITH NONCROSS-LINKING IONS PRESENT IN THE EYE WITH SAID DISPLACEMENT RATE CORRESPONDING TO THE EXTENT OF POLYVALENT IONS CROSS-LINKED, AND WHEREIN THE MEMBRANE MATERIAL CONTINUOUSLY METERS THEFLOW OF A THERAPEUTICALLY EFFECTIVE AMOUNT OF SAID DRUG FROM THE RESERVOIR TO THE EYE OF THEPATIENT AT A CONTROLLED RATE OVER A PROLONGED PERIOD OF TIME.

2. An ocular delivery device for the sustained administration of a predetermined dosage of an ophthalmic drug selected from the group consisting of pilocarpine and hydrocortisone when placed in the sac of a mammalian eye bounded by the surface of the bulbar conjunctiva of the sclera of the eyeball and the palpebral conjunctiva of the lid, comprising a body of a biocompatible bioerodible drug release rate controlling material containing said drug therein, said material comprising a polyvalent ion cross-linked anionic polyelectrolyte, with said polyelectrolyte cross-linked solely with a polvalent cation selected from the group consisting of aluminum, barium, cadmium, calcium, copper, iron and zinc, said anionic polyelectrolyte a water-soluble member selected from the group consisting of agar, algin, alginic acid, carrageenan, cellulose, gum arabic, gum ghatti, pectic acid, pectin, pectinic acid and polysaccharide, which cross-linked material bioerodes to nontoxic materials when placed in the eye in response to the biological eye environment by a process of polyvalent ion displacement of the cross-linked cation with noncross-linking ions present in the environment, with the bioerosion rate corresponding to the extent of polyvalent ion cross-linked, and wherein the ocular device continuously meters a flow of a therapeutically effective amount of said drug from the device at a controlled rate over a prolonged period of time.

3. An ocular delivery device in accordance with claim 2 for the sustained administration of a predetermined dosage of an ocular drug selected from the group consisting of pilocarpine and hydrocortisone when placed in the sac of a mammalian eye bounded by the surface of the bulbar conjunctiva of the sclera of the eyeball and the palpebral conjunctiva of the lid comprising a body of biocompatible bioerodible drug release rate controlling material containing from 5 percent to 90 percent of ocular drug based on the weight of the material with from one-tenth percent to 35 percent of drug dissolved in the material, said material comprising a polyvalent ion cross-linked anionic polyelectrolyte, with said polyelectrolyte cross-linked with from two-tenths to three equivalents of a cross-linking agent selected from the group consisting of aluminum, barium, cadmium, calcium, copper, iron and zinc for each equivalent of polyelectrolyte, with said polyelectrolyte selected from the group consisting of agar, algin, alginic acid, carrageenan, cellulose, gum arabic, gum ghatti, pectic acid, pectin, pectinic acid and polysaccharide, which material bioerodes to physiologically acceptable materials when placed in an eye in response to the biological environment of the eye by a process of polyvalent ion displacement of the cross-linked ion with noncross-linking ions in situ, and wherein the device concurrent with the displacement continuously meters the flow of a therapeutically effective amount of said drug from the device to the eye at a controlled rate over a prolonged period of time.

4. An ocular delivery device for the sustained administration of a predetermined dosage of an ophthalmic drug when placed in a mammalian eye comprising a body shaped and adapted for insertion and comfortable retention in the eye, the device made of a biocompatible bioerodible drug release rate controlling material containing an ocular drug formulation of from 5 percent to 90 percent oF drug based on the weight of the material with from one-tenth percent to 35 percent of drug dissolved in the material with the drug a member selected from the ophthalmic drug group consisting of antibiotic, antibacterial, antiviral, antiallergenic, anti-inflammatory, miotic, anticholinesterase, decongestant, and sympathomimetic, said material comprising a polyvalent ion cross-linked anionic polyelectrolyte with the polyelectrolyte cross-linked with from two-tenths to three equivalents of a cross-linking agent selected from the group consisting of polyvalent cations aluminum, barium, cadmium, calcium, copper, iron and zinc for each equivalent of a member selected from the group consisting of agar, algin, alginic acid, carrageenan, cellulose, gum arabic, gum ghatti, pectic acid, pectin, pectinic acid and polysaccharide polyelectrolyte which cross-linked polyelectrolyte material is hydrophilic insoluble in the cross-linked form, initially imperforate, when placed in the eye absorbs fluid, swells and forms a fluid impregnated microporous structure and bioerodes in from 4 hours to 30 days into innocuous products in response to the biological environment by a process of polvyalent ion displacement with noncross-linking ions in the eye, and wherein the body concurrent with the displacement continuously meters the flow of a therapeutically effective amount of said ophthalmic drug from the device to the eye at a controlled rate over a prolonged period of time.

5. An ocular bioerodible delivery device for the sustained administration of a predetermined dosage of ophthalmic drug to the eye of a mammalian patient comprising a matrix of a polyvalent cation cross-linked anionic polyelectrolyte material with the polyelectrolyte cross-linked with from two-tenths to three equivalents cross-linking agents selected solely from the polyvalent cations aluminum, barium, cadmium, calcium, copper, iron and zinc for each equivalent of a physiologically acceptable anionic polyelectrolyte selected from the group consisting of agar, algin, alginic acid, carrageenan, cellulose, gum arabic, gum ghatti, pectic acid, pectin, pectinic acid and polysaccharide, with the meterial having distributed throughout a plurality of reservoirs, with each of the reservoirs comprised of an eye formulation confined within a release rate controlling material, the reservoir characterized by being (1) a microcapsule of an initial size and configuration such as to be capable of being eliminated from the ocular cavity through the punctum with tear fluid or, (2) a microcapsule of biodegradable material, the matrix material permeable to the passage of drug at a higher rate than through the drug release rate controlling material with the matrix material bioeroding to essentially nontoxic material in response to the biological environment of the eye by a process of polyvalent ion displacement with noncross-linking ions present in the eye, with the release rate controlling material metering a therapeutically effective amount of drug from the reservoir to the eye of the patient at a controlled rate over a prolonged period of time.