# US 10,307,379 B2 · Donepezil transdermal delivery system

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- Number: US 10,307,379 B2
- Document ID: US10307379B2
- Status: Granted
- Kind: B2
- Application number: 15/957,858
- Filed: 2018-04-19
- Published: 2018-08-23
- Granted: 2019-06-04
- Earliest claimed: 2016-07-27
- Assignees: Corium, Inc.
- Applicants: Corium, Inc.
- Inventors: Eun Soo Lee; Amit K. Jain; Parminder Singh
- Web page: https://patentgrep.com/patent/US10307379B2

## CPC

- A61K 9/7038: {Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer}
- A61K 9/7023: {Transdermal patches and similar drug-containing composite devices, e.g. cataplasms (galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006)}
- A61K 9/7053: {obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene}
- 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 9/7092: {Transdermal patches having multiple drug layers or reservoirs, e.g. for obtaining a specific release pattern, or for combining different drugs}
- A61K 31/00: Medicinal preparations containing organic active ingredients
- A61K 31/13: Amines {(A61K31/04 takes precedence)}
- A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone}
- A61K 31/18: Sulfonamides (compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63)
- A61K 31/27: of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
- A61K 31/445: Non condensed piperidines, e.g. piperocaine
- A61K 47/02: Inorganic compounds
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone}
- A61P 13/00: Drugs for disorders of the urinary system
- A61P 13/02: of urine or of the urinary tract, e.g. urine acidifiers
- A61P 13/08: of the prostate
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/02: for peripheral neuropathies
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/22: Anxiolytics
- A61P 25/24: Antidepressants
- A61P 25/26: Psychostimulants, e.g. nicotine, cocaine
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 25/36: Opioid-abuse
- A61P 35/00: Antineoplastic agents
- C08K 5/0016: {Plasticisers}
- A61K 31/045: Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- 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
- C08K: Use of inorganic or non-macromolecular organic substances as compounding ingredients (paints, inks, varnishes, dyes, polishes, adhesives C09)

## Abstract

A transdermal delivery system for systemic delivery of donepezil is described, where the system comprises an adhesive matrix drug reservoir layer comprised of a copolymer of acrylic acid/vinyl acetate, triethyl citrate, and donepezil base generated in situ by reaction of donepezil HCl and an alkaline salt. The system is provided for treatment of Alzheimer's disease, and achieves transdermal delivery of the therapeutic agent at steady state that is bioequivalent to administration of the therapeutic agent orally.

## Claims

### Claim 1

A composition, comprising:
a drug reservoir comprised of a molar amount of donepezil HCl, an equimolar or less than equimolar amount of a pharmaceutically acceptable alkaline salt, a solvent composition comprising a hydrophilic solvent, and an acrylate copolymer, wherein the alkaline salt is sodium bicarbonate or potassium bicarbonate; and
a skin contact adhesive comprising one or more of (i) triethyl citrate, (ii) sorbitan monolaurate, and (iii) lauryl lactate, wherein reaction of donepezil HCl and the alkaline salt generates a therapeutically effective amount of donepezil base in situ in the drug reservoir when the skin contact adhesive is attached to skin of a subject.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the solvent composition comprises one or more of triethyl citrate, sorbitan monolaurate, and lauryl lactate.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the solvent composition comprises between about 8-12 wt % triethyl citrate, between about 1.5-2.5 wt % sorbitan monolaurate, and between about 1-10 wt % lauryl lactate.

### Claim 4 (depends on 3)

The composition of claim 3, wherein the skin contact adhesive comprises between about 1-20 wt % triethyl citrate, between about 0.01-5 wt % sorbitan monoloaurate, and between about 0.1-10 wt % lauryl lactate.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the hydrophilic solvent is selected from the group consisting of polyethylene glycol, propylene glycol, glycerin, acetonitrile, 1-propanol, and N,N-dimethylformamide.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the hydrophilic solvent is glycerin.

### Claim 7 (depends on 6)

The composition of claim 6, comprising between about 5-15 wt % glycerin.

### Claim 8 (depends on 1)

The composition of claim 1, comprising between about 1-5 wt % sodium bicarbonate.

### Claim 9 (depends on 1)

The composition of claim 1, comprising between about 5-25 wt % donepezil HCl.

### Claim 10

A composition, comprising:
a drug reservoir comprised of a molar amount of a donepezil salt, an equivalent or less than equivalent amount of a pharmaceutically acceptable alkaline salt, a solvent composition comprising a hydrophilic solvent, and an acrylate copolymer, wherein the alkaline salt is sodium bicarbonate or potassium bicarbonate; and
a skin contact adhesive comprising one or more of (i) triethyl citrate, (ii) sorbitan monolaurate, and (iii) lauryl lactate, wherein reaction of the donepezil salt and the alkaline salt generates a therapeutically effective amount of donepezil base in situ in the drug reservoir when the skin contact adhesive is attached to skin of a subject.

### Claim 11 (depends on 10)

The composition of claim 10, wherein the solvent composition comprises between about 8-12 wt % triethyl citrate, between about 1.5-2.5 wt % sorbitan monolaurate, and between about 1-10 wt % lauryl lactate.

### Claim 12 (depends on 11)

The composition of claim 11, wherein the skin contact adhesive comprises between about 1-20 wt % triethyl citrate, between about 0.01-5 wt % sorbitan monoloaurate, and between about 0.1-10 wt % lauryl lactate.

### Claim 13 (depends on 10)

The composition of claim 10, wherein the hydrophilic solvent is selected from the group consisting of polyethylene glycol, propylene glycol, glycerin, acetonitrile, 1-propanol, and N,N-dimethylformamide.

### Claim 14 (depends on 10)

The composition of claim 10, wherein the hydrophilic solvent is glycerin.

### Claim 15 (depends on 14)

The composition of claim 14, comprising between about 5-15 wt % glycerin.

### Claim 16 (depends on 10)

The composition of claim 10, comprising between about 1-5 wt % sodium bicarbonate.

### Claim 17 (depends on 10)

The composition of claim 10, wherein the donepezil salt is donepezil HCl.

### Claim 18 (depends on 17)

The composition of claim 17, comprising between about 5-25 wt % donepezil HCl.