# US 2014/0154321 A1 · Sustained release delivery devices

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- Number: US 2014/0154321 A1
- Document ID: US20140154321A1
- Status: Published application
- Kind: A1
- Application number: 14/091,553
- Filed: 2013-11-27
- Published: 2014-06-05
- Earliest claimed: 2009-12-23
- Assignees: pSivida US, Inc.
- Applicants: pSivida US, Inc.
- Inventors: Paul Ashton
- Web page: https://patentgrep.com/patent/US20140154321A1

## CPC

- A61K 9/14: Particulate form, e.g. powders, {Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles (microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51)}
- 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)}
- A61K 9/0048: {Eye, e.g. artificial tears}
- A61K 9/0051: {Ocular inserts or implants}
- A61K 9/0092: {Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes}
- A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
- A61K 31/58: containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin (digitoxin {A61K31/7048})
- A61K 31/74: Synthetic polymeric materials
- A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone}
- A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 27/00: Drugs for disorders of the senses
- A61P 27/02: Ophthalmic agents
- A61P 27/06: Antiglaucoma agents or miotics
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

An injectable drug delivery includes a core containing one or more drugs and one or more polymers. The core may be surrounded by one or more polymer outer layers (referred to herein as “coatings,” “skins,” or “outer layers”). In certain embodiments, the device is formed by extruding or otherwise preforming a polymeric skin for a drug core. The drug core may be co-extruded with the skin, or inserted into the skin after the skin has been extruded, and possibly cured. In other embodiments, the drug core may be coated with one or more polymer coatings. These techniques may be usefully applied to fabricate devices having a wide array of drug formulations and skins that can be selected to control the release rate profile and various other properties of the drugs in the drug core in a form suitable for injection using standard or non-standard gauge needles.

## Claims

### Claim 1

A drug delivery device shaped and sized for injection comprising:
a core including one or more drugs; and
a polymeric skin at least partially surrounding the core, the skin comprising a first one or more polymers.

### Claim 2 (depends on 1)

The device of claim 1, wherein the core comprises a matrix of the one or more drugs and a second one or more polymers.

### Claim 3 (depends on 2)

The device of claim 2, wherein at least one of the second one or more polymers is bioerodible.

### Claim 4 (depends on 2)

The device of claim 2, wherein the second one or more polymers comprises at least one of poly(vinyl acetate) (PVAC), poly(caprolactone) (PCL), polyethylene glycol (PEG), poly(dl-lactide-co-glycolide) (PLGA), ethylene vinyl acetate polymer (EVA), polylvinyl alcohol) (PVA), poly(lactic acid) (PLA), poly(glycolic acid) (PGA), polyalkyl cyanoacralate, polyurethane, or nylon, or a copolymer thereof.

### Claim 5 (depends on 1)

The device of claim 1, wherein the one or more drugs includes at least one of a codrug or a prodrug.

### Claim 6 (depends on 1)

The device of claim 1, wherein the core comprises a biocompatible gelling formulation.

### Claim 7 (depends on 1)

The device of claim 1, wherein the one or more drugs includes a steroid.

### Claim 8 (depends on 7)

The device of claim 7, wherein the steroid comprises at least one of loteprednol etabonate, triamcinolone acetonide (TA), fluocinolone acetonide, or anacortave acetate.

### Claim 9 (depends on 1)

The device of claim 1, wherein at least one of the one or more drugs comprises an anti-metabolite.

### Claim 10

(canceled)

### Claim 11 (depends on 1)

The device of claim 1, wherein at least one of the one or more drugs comprises an adrenergic agent.

### Claim 12

(canceled)

### Claim 13 (depends on 1)

The device of claim 1, wherein at least one of the one or more drugs comprises a carbonic anhydrase inhibitor.

### Claim 14

(canceled)

### Claim 15 (depends on 1)

The device of claim 1, wherein at least one of the one or more drugs comprises an antiviral agent.

### Claim 16

(canceled)

### Claim 17 (depends on 1)

The device of claim 1 wherein the polymeric skin is one of impermeable, semi-permeable, or permeable to at least one of the one or more drugs.

### Claim 18 (depends on 1)

The device of claims 1, wherein the polymeric skin comprises at least one of PVAC, PCL, PEG, PLGA, EVA, PVA, PLA, PGA, polyalkyl cyanoacralate, polyurethane, or nylon, or a copolymer thereof.

### Claim 19 (depends on 2)

The device of claim 2, wherein at least one of the first one or more polymers and the second one or more polymers is bioerodible.

### Claim at position 20

20-23. (canceled)

### Claim 24 (depends on 1)

The device of claim 1, wherein the polymeric skin further comprises at least one drug.

### Claim 25

(canceled)

### Claim 26 (depends on 1)

The device of claim 1, wherein the device is shaped and sized for injection through at least one of a cannula having a size from about 30 gauge to about 15 gauge or a needle having a size from about 30 gauge to about 15 gauge.

### Claim 27 (depends on 1)

The device of claim 1, wherein the device is shaped and sized for at least one of periocular or intraocular injection.

### Claim 28

(canceled)

### Claim 29 (depends on 1)

The device of claim 1, wherein the device provides sustained release of the one or more drugs when exposed to a biological medium.

### Claim 30 (depends on 2)

The device of claim 2, further comprising a second polymeric skin.

### Claim 31 (depends on 30)

The device of claim 30, wherein the polymeric skin has a different permeability to the one or more drugs than the second polymeric skin, and the core is completely covered by a combination of the polymeric skin and the second polymeric skin.

### Claim 32 (depends on 30)

The device of claim 30, wherein at least one of the polymeric skin, or the second polymeric skin is bioerodible.

### Claim 33 (depends on 32)

The device of claim 32, wherein a release rate of at least one of the one or more drugs is influenced by an erosion of at least one of the polymeric skin or the second polymeric skin.

### Claim 34 (depends on 32)

The device of claim 32, wherein a release rate of at least one of the one or more drugs is independent of an erosion of at least one of the polymeric skin or the second polymeric skin.

### Claim 35 (depends on 31)

The device of claim 31, wherein each of the core, the polymeric skin, and the second polymeric skin is bioerodible.

### Claim 36 (depends on 31)

The device of claim 31, wherein a release rate of at least one of the one or more drugs is controlled by at least one of the permeability of the second polymeric skin to the at least one of the one or more drugs and a surface area of the core that is not covered by the polymeric skin.

### Claim 37 (depends on 31)

The device of claim 31, wherein at least one of the polymeric skin and the second polymeric skin prevent direct interaction of biological fluids with the core.

### Claim 38 (depends on 31)

The device of claim 31, wherein a release rate of at least one of the one or more drugs is controlled by a surface area of the core.

### Claim 39 (depends on 31)

The device of claim 31, wherein a release rate of at least one of the one or more drugs is not substantially influenced by diffusion of the at least one drug through the core.

### Claim 40 (depends on 31)

The device of claim 31, wherein a release rate of at least one of the one or more drugs is significantly influenced by diffusion of the at least one drug through the core.

### Claim 41 (depends on 31)

The device of claim 31, wherein a release rate of at least one of the one or more drugs is significantly influenced by a solubility of the at least one drug within the core.

### Claim 42 (depends on 31)

The device of claim 31, wherein at least one of the one or more drugs is more stable within the device than in a biological medium.

### Claim 43 (depends on 31)

The device of claim 31, wherein the device provides increased stability of at least one of the one or more drugs to a curing process.

### Claim 44 (depends on 31)

The device of claim 31, wherein the device provides increased stability of at least one of the one or more drugs to storage.

### Claim 45 (depends on 1)

A device of claim 1, wherein the device releases the drug at a rate of less than about 0.5, less than about 0.4, less than about 0.3, less than about 0.2, or even less than about 0.1 μg/day.

### Claim 46 (depends on 1)

A method for treating diabetic macular edema, comprising administering a device of claim 1.

### Claim 47 (depends on 46)

The method of claim 46, wherein the drug is released at a rate of less than about 0.4 μg/day steadily and continuously for a period of at least six months.

### Claim 48 (depends on 47)

The method of claim 47, wherein the method comprises treating said diabetic macular edema with fewer side effects.

### Claim 49 (depends on 48)

The method of claim 48, wherein said side effects include increased IOP.

### Claim 50

A drug delivery device comprising:
a drug core, preferably comprising a glucocorticoid, such as fluocinolone acetonide;
a polymer tube, preferably a tube impermeable to the passage of drug, such as a tube comprising polyimide; and
an outer layer covering at least one end, preferably covering both ends of the device and a portion of the tube, wherein the outer layer is permeable to the passage of drug;
wherein the device releases the drug at a rate of less than about 0.5, about 0.4, about 0.3, about 0.2, or even less than about 0.1 μg/day.

### Claim 51 (depends on 50)

A device of claim 50, wherein the outer layer comprises polyvinyl alcohol.

### Claim 52 (depends on 50, 51)

A device of claim 50 or 51, wherein the device releases the drug at a substantially continuous release rate.

### Claim 53 (depends on 50, 51, 52)

A method for the treatment of diabetic macular edema, comprising administering a device of any one of claims 50-52.

### Claim 54

A method for treating an eye disease or disorder with fewer side effects, comprising administering a drug to an eye of a patient in need thereof daily for a period of at least 3 months, wherein said drug is administered at a release rate of less than or equal to 0.4 μg/day to treat said disease or disorder without causing a significant increase in IOP in a substantial percentage of treated patients.

### Claim 55 (depends on 54)

The method of claim 54, wherein the disease or disorder of the eye is macular edema or macular degeneration.

### Claim 56 (depends on 54, 55)

The method of claim 54 or 55, wherein said drug is administered at a release rate of less than or equal to 0.3 μg/day, 0.2 μg/day, or 0.1 μg/day.

### Claim 57 (depends on 54, 55, 56)

The method of any of claims 54-56, wherein administration of said drug causes a significant increase in IOP in less than 20% of treated patients.

### Claim 58 (depends on 54, 55, 56)

The method of any of claims 54-56, wherein administration of said drug causes a significant increase in IOP in less than 10% of treated patients.

### Claim 59 (depends on 54, 55, 56)

The method of any of claims 54-56, wherein administration of said drug causes a significant increase in IOP in less than 5% of treated patients.

### Claim 60 (depends on 54, 55, 56)

The method of any of claims 54-56, wherein increase in IOP occurs at a low enough frequency as to be considered a rare event associated with treatment.

### Claim 61

A method for decreasing excess foveal thickness in a patient in need thereof, comprising administering a drug to an eye of said patient for a period of at least 3 months, wherein said drug is administered at a release rate of less than or equal to 0.4 μg/day to decrease excess foveal thickness.

### Claim 62 (depends on 54)

The method of claim 54, wherein the drug consists of fluocinolone acetonide.

### Claim 63 (depends on 55)

The method of claim 55, wherein the disease or disorder of the eye is diabetic macular edema.

### Claim 64 (depends on 54)

The method of claim 54, wherein the drug is released steadily and continuously for a period of up to thirty-six months.