# US 2019/0167655 A1 · Transdermal Administration Of Fentanyl And Analogs Thereof

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- Number: US 2019/0167655 A1
- Document ID: US20190167655A1
- Status: Published application
- Kind: A1
- Application number: 16/271,002
- Filed: 2019-02-08
- Published: 2019-06-06
- Earliest claimed: 2001-03-16
- Applicants: Alza Corporation
- Inventors: Subramanian VENKATRAMAN; Shaoling Li; Robert M. Gale; Jane Stepic; William W. Van Osdol
- Web page: https://patentgrep.com/patent/US20190167655A1

## CPC

- A61K 31/4468: having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
- A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)}
- A61K 9/703: {characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches}
- A61K 9/7038: {Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer}
- A61K 9/7061: {Polyacrylates}
- A61K 9/7084: {Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches}
- A61K 31/4535: containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
- A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- A61K 47/22: Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
- 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 25/04: Centrally acting analgesics, e.g. opioids
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 29/02: without antiinflammatory effect
- 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

A method and a non-rate controlled, monolithic, subsaturated patch for transdermally administering fentanyl and analogs thereof, for analgetic purposes, to a subject through skin over an extended period of time are disclosed.

## Claims

### Claim 1

A transdermal patch for administering fentanyl or an analog thereof through the skin comprising:
(a) a backing layer; and
(b) a polyacrylate adhesive reservoir disposed on the backing layer, at least the skin contacting surface of said reservoir being adhesive; said reservoir being 0.0125 mm to 0.1 mm thick, comprising a single phase polymeric composition free of undissolved fentanyl or an analog thereof and containing an amount of fentanyl or an analog thereof sufficient to induce and maintain analgesia in a human for at least three days.

### Claim 2 (depends on 1)

The patch of claim 1 wherein the reservoir contains fentanyl and has an area of 1 to 150 cm2 or contains sufentanil and has an area of 0.5 to 40 cm2.

### Claim 3 (depends on 1)

The patch of claim 1 wherein the reservoir contains fentanyl and has an area of 1 to 150 cm2 and contains no permeation enhancer.

### Claim 4 (depends on 1)

The patch of claim 1 wherein said patch exhibits a normalized Cmax of 3.3 to 82.5 ng/(ml(mg/h)).

### Claim 5 (depends on 1)

The patch of claim 1 wherein the patch exhibits a steady state drug flux of 0.1 to 20 μg/(cm2 hr).

### Claim 6 (depends on 1)

The patch of claim 1 wherein said patch exhibits a standardized Cmax of 0.001 to 0.2 ng/(ml-cm2).

### Claim 7 (depends on 1)

The patch of claim 1 wherein the reservoir contains sufentanil and has an area of 0.5 to 40 cm2.

### Claim 8 (depends on 1)

The patch of claim 1 wherein said reservoir comprises an amount of dissolved fentanyl analog sufficient to induce and maintain analgesia for 3-7 days.

### Claim 9 (depends on 8)

The patch of claim 8 wherein said fentanyl analog is selected from the group consisting of alfentanil, lofentanil, remifentanil and sufentanil.

### Claim 10 (depends on 8)

The patch of claim 8 wherein said reservoir comprises a polymer having a solubility for fentanyl and analogs thereof of 1 wt % to 25 wt %.

### Claim 11 (depends on 8)

The patch of claim 8 wherein the reservoir comprises 0.05 to 1.75 mg/cm2 of fentanyl analog.

### Claim 12 (depends on 1)

The patch of claim 1 wherein said adhesive has a Tg less than −10° C.; and fentanyl has a solubility of at least 4 wt % in said reservoir.

### Claim 13 (depends on 1)

The patch of claim 1 wherein the reservoir comprises 0.1 to 0.5 mg/cm2 of fentanyl base.

### Claim 14 (depends on 1)

The patch of claim 1 wherein the reservoir further comprises an enhancer.

### Claim 15 (depends on 1)

The patch of claim 1 wherein the backing layer comprises a polymer selected from the group consisting of polyurethane, polyvinyl acetate, polyvinylidene chloride, polyethylene, polyethylene terephthalate (PET), PET-polyolefin laminates, and polybutylene terephthalate.

### Claim 16 (depends on 1)

The patch of claim 1 wherein the backing layer has a thickness of 0.012 mm to 0.125 mm.

### Claim 17 (depends on 1)

The patch according to claim 1 wherein the polyacrylate adhesive is a copolymer or a terpolymer adhesive of monomer components at least two of which are selected from the group consisting of acrylic acid, methacrylic acid, methoxyethyl acrylate, ethyl acrylate, butyl acrylate, butyl methacrylate, hexyl acrylate, hexyl methacrylate, 2-ethylbutyl acrylate, 2-ethylbutyl methacrylate, isooctyl acrylate, isooctyl methacrylate, 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate, decyl acrylate, decyl methacrylate, dodecyl acrylate, dodecyl methacrylate, tridecyl acrylate, tridecyl methacrylate, hydroxyethyl acrylate, hydroxypropyl acrylate, acrylamide, dimethylacrylamide, acrylonitrile, dimethylaminoethyl acrylate, dimethylaminoethyl methacrylate, tert-butylaminoethyl acrylate, tert-butylaminoethyl methacrylate, methoxyethyl acrylate and methoxyethyl methacrylate.

### Claim 18 (depends on 1)

The patch according to claim 1 wherein the patch is monolithic and the reservoir when deployed in use adheres to the skin to maintain analgesia in a human for at least three days.

### Claim 19

A monolithic transdermal patch for administering fentanyl through the skin comprising:
(a) a backing layer; and
(b) a polyacrylate adhesive reservoir disposed on the backing layer, at least the skin contacting surface of said reservoir being adhesive; said reservoir being 0.0125 mm to 0.1 mm thick, comprising a single phase polymeric composition to be free of undissolved components and containing an amount of fentanyl sufficient to induce and maintain analgesia in a human for at least three days.

### Claim 20

A transdermal patch for administering sufentanil through the skin comprising:
(a) a backing layer; and
(b) polyacrylate adhesive reservoir disposed on the backing layer, at least the skin contacting surface of said reservoir being adhesive; said reservoir being 0.0125 mm to 0.1 mm thick, comprising a single phase polymeric composition to be free of undissolved sufentanil and containing an amount of sufentanil sufficient to induce and maintain analgesia in a human for at least three days.

### Claim 21 (depends on 1)

The patch of claim 1 wherein said reservoir comprises an amount of dissolved fentanyl sufficient to induce and maintain analgesia for 3-7 days.

### Claim 22 (depends on 21)

The patch of claim 21 wherein the reservoir comprises 0.05 to 1.75 mg/cm2 of fentanyl.

### Claim 23 (depends on 1)

The patch according to claim 1 wherein said reservoir does not include polysiloxane.

### Claim 24 (depends on 1)

The patch according to claim 1 wherein said reservoir comprises 7 to 12 wt % fentanyl or analog thereof.

### Claim 25 (depends on 1)

The patch according to claim 1 wherein the polyacrylate adhesive includes the monomers 2-ethylhexyl acrylate, hydroxyethylacrylate, and vinyl acetate.

### Claim 26 (depends on 1)

The patch according to claim 1 wherein the polyacrylate adhesive does not include isooctyl acrylate.

### Claim 27 (depends on 19)

The patch according to claim 19 wherein said reservoir does not include polysiloxane.

### Claim 28 (depends on 19)

The patch according to claim 19 wherein the polyacrylate adhesive includes the monomers 2-ethylhexyl acrylate, hydroxyethylacrylate, and vinyl acetate.

### Claim 29 (depends on 19)

The patch according to claim 19 wherein said reservoir comprises 7 to 12 wt % fentanyl.

### Claim 30 (depends on 19)

The patch according to claim 19 wherein the polyacrylate adhesive does not include isooctyl acrylate.

### Claim 31 (depends on 20)

The patch according to claim 20 wherein said reservoir does not include polysiloxane.

### Claim 32 (depends on 20)

The patch according to claim 20 wherein the polyacrylate adhesive includes the monomers 2-ethylhexyl acrylate, hydroxyethylacrylate, and vinyl acetate.

### Claim 33 (depends on 20)

The patch according to claim 20 wherein the polyacrylate adhesive does not include isooctyl acrylate.

### Claim 34 (depends on 20)

The patch according to claim 20 wherein said reservoir comprises 7 to 12 wt % sufentanyl thereof.