# US 11,896,562 B2 · Oral amphetamine composition

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- Number: US 11,896,562 B2
- Document ID: US11896562B2
- Status: Granted
- Kind: B2
- Application number: 17/493,949
- Filed: 2021-10-05
- Published: 2022-01-27
- Granted: 2024-02-13
- Earliest claimed: 2017-03-10
- Assignees: Adare Pharmaceuticals, Inc.
- Applicants: Adare Pharmaceuticals, Inc.
- Inventors: Gopi Venkatesh; Michelle Schilling
- Web page: https://patentgrep.com/patent/US11896562B2

## CPC

- A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone}
- A61K 9/0056: {Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals}
- A61K 9/2081: {with microcapsules or coated microparticles according to A61K9/50}
- A61K 9/2095: {Tabletting processes}
- A61K 9/5026: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/5042: {Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose}
- A61K 9/5047: {Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose}
- A61K 9/5073: {having two or more different coatings optionally including drug-containing subcoatings}
- A61K 9/5089: {Processes}
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- 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)

## Abstract

In various embodiments, the present invention is directed to oral pharmaceutical compositions. For example, in some embodiments, the present invention is directed to taste-masked compositions. In some embodiments, the taste masked compositions comprise a highly water soluble drug such as amphetamine, e.g., in the form of a salt such as amphetamine sulfate. In various embodiments, the present invention is directed to taste-masked, orally disintegrating compositions.

## Claims

### Claim 1

A method of treating attention deficit-hyperactivity disorder (ADHD) in a subject in need thereof, the method comprising, administering to the subject an orally disintegrating pharmaceutical composition comprising;
(a) taste-masked drug containing particles comprising:
(i) drug-containing core particles comprising a therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof and at least one excipient;
(ii) a first taste-masking membrane comprising a water-insoluble polymer and excluding pharmaceutically acceptable gastrosoluble polymers, wherein the first taste-masking membrane is disposed directly on the drug-containing core particles; and
(iii) a second taste-masking membrane comprising a water-insoluble polymer and a gastrosoluble polymer at a ratio ranging from about 95/5 to about 50/50 by wt., wherein the second taste-masking membrane is disposed directly on the first taste-masking membrane,
wherein the water-insoluble polymer is each independently ethylcellulose, cellulose acetate, cellulose acetate butyrate, polyvinyl acetate, or a neutral acrylate-methacrylate copolymer;
(b) a disintegrant;
(c) a sugar alcohol or saccharide, or mixture thereof; and
wherein if the orally disintegrating pharmaceutical composition comprises 30 mg of racemic amphetamine sulfate, after administration the orally disintegrating pharmaceutical composition provides one or more of the following:
an AUCinf ranging from about 80% to about 125% of about 400-600 hr*ng/mL;
a Cmax ranging from about 80% to about 125% of about 25-35 ng/mL; or
a Tmax ranging from about 80% to about 125% of about 2-4 hrs.

### Claim 2 (depends on 1)

The method of claim 1, wherein the first taste-masking membrane has a thickness of from about 5% to about 10% by wt. of the taste-masked drug containing particle.

### Claim 3 (depends on 1)

The method of claim 1, wherein the water-insoluble polymer in the first taste-masking membrane is ethylcellulose.

### Claim 4 (depends on 1)

The method of claim 1, wherein the water-insoluble polymer in the second taste-masking membrane is ethylcellulose and the gastrosoluble polymer is aminoalkyl methacrylate copolymer.

### Claim 5 (depends on 2)

The method of claim 2, wherein the second taste-masking membrane has a thickness of from about 15% to about 30% by wt. of the taste-masked drug containing particle.

### Claim 6 (depends on 1)

The method of claim 1, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof in the drug containing core particles is a dose equivalent to 30 mg of racemic amphetamine sulfate, wherein after administration, the orally disintegrating pharmaceutical composition provides two or more of the following:
an AUCinf ranging from about 80% to about 125% of about 400-600 hr*ng/mL;
a Cmax ranging from about 80% to about 125% of about 25-35 ng/mL; or
a Tmax ranging from about 80% to about 125% of about 2-4 hrs.

### Claim 7 (depends on 1)

The method of claim 1, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof in the drug containing core particles is a dose equivalent to 30 mg of racemic amphetamine sulfate, wherein after administration, the orally disintegrating pharmaceutical composition provides the following:
an AUCinf ranging from about 80% to about 125% of about 400-600 hr*ng/mL;
a Cmax ranging from about 80% to about 125% of about 25-35 ng/mL; and
a Tmax ranging from about 80% to about 125% of about 2-4 hrs.

### Claim 8 (depends on 3)

The method of claim 3, wherein the ethylcellulose in the first taste- masking membrane has a viscosity of about 100 cps.

### Claim 9 (depends on 4)

The method of claim 4, wherein the ethylcellulose in the second taste- masking membrane has a viscosity of about 10 cps.

### Claim 10 (depends on 1)

The method of claim 1, wherein the water-insoluble polymer in the first taste-masking membrane is ethylcellulose having a viscosity of about 100 cps, and the water-insoluble polymer in the second taste-masking membrane is ethylcellulose having a viscosity of about 10 cps.

### Claim 11 (depends on 1)

The method of claim 1, wherein the (i) disintegrant, and (ii) the sugar alcohol, saccharide, or combination thereof are present together in the form of rapidly dispersing microgranules.

### Claim 12 (depends on 11)

The method of claim 11, wherein the rapidly dispersing microgranules have an average particle size of not more than about 300 μm.

### Claim 13 (depends on 12)

The method of claim 12, wherein the disintegrant has an average particle diameter of not more than about 30 μm.

### Claim 14 (depends on 12)

The method of claim 12, wherein the sugar alcohol and/or saccharide has an average particle diameter of not more than about 30 μm.

### Claim 15 (depends on 1)

The method of claim 1, wherein taste-masked drug containing particles have an average particle size of not more than about 400 μm.

### Claim 16 (depends on 1)

The method of claim 1, wherein the excipient in the drug-containing core particles is mannitol, the racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof is racemic amphetamine sulfate, and the drug-containing core particles are an amphetamine sulfate-mannitol granulate.

### Claim 17 (depends on 1)

The method of claim 1, wherein the excipient in the drug-containing core particle is a bead, the racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof is racemic amphetamine sulfate, and the drug-containing core particles are an amphetamine sulfate layered bead.

### Claim 18 (depends on 1)

The method of claim 1, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof is a dose equivalent to about 30 mg.

### Claim 19 (depends on 1)

The method of claim 1, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof in the drug containing core particles is in the range of from about 5 mg to about 40 mg.

### Claim 20 (depends on 19)

The method of claim 19, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof in the drug containing core particles is a dose equivalent to about 5 mg of racemic amphetamine sulfate.

### Claim 21 (depends on 19)

The method of claim 19, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof in the drug containing core particles is a dose equivalent to about 10 mg of racemic amphetamine sulfate.

### Claim 22 (depends on 19)

The method of claim 19, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof in the drug containing core particles is a dose equivalent to about 15 mg of racemic amphetamine sulfate.

### Claim 23 (depends on 19)

The method of claim 19, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof in the drug containing core particles is a dose equivalent to about 20 mg of racemic amphetamine sulfate.

### Claim 24 (depends on 19)

The method of claim 19, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof in the drug containing core particles is a dose equivalent to about 25 mg of racemic amphetamine sulfate.

### Claim 25 (depends on 19)

The method of claim 19, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof in the drug containing core particles is a dose equivalent to about 30 mg of racemic amphetamine sulfate.

### Claim 26 (depends on 19)

The method of claim 19, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof in the drug containing core particles is a dose equivalent to about 40 mg of racemic amphetamine sulfate.

### Claim 27 (depends on 1)

The method of claim 1, wherein the gastrosoluble polymer in the second taste- masking membrane is maltrin, an aminoalkyl methacrylate copolymer or, polyvinylacetal diethylaminoacetate.

### Claim 28 (depends on 5)

The method of claim 5, wherein the gastrosoluble polymer in the second taste- masking membrane is maltrin, an aminoalkyl methacrylate copolymer or, polyvinylacetal diethylaminoacetate.