# US 10,441,554 B2 · Oral amphetamine composition

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- Number: US 10,441,554 B2
- Document ID: US10441554B2
- Status: Granted
- Kind: B2
- Application number: 16/000,322
- Filed: 2018-06-05
- Published: 2018-11-01
- Granted: 2019-10-15
- Earliest claimed: 2017-03-10
- Assignees: Adare Pharmaceuticals, Inc.
- Applicants: Adare Pharmaceuticals, Inc.
- Inventors: Gopi M. Venkatesh; Michelle Schilling
- Web page: https://patentgrep.com/patent/US10441554B2

## 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

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 ethylcellulose and excluding pharmaceutically acceptable gastrosoluble polymers, wherein the first taste-masking membrane is disposed on the drug-containing core particles and has a membrane thickness of from about 5% to about 10% by wt. of the taste-masked drug containing particle, and
(iii) a second taste-masking membrane comprising ethylcellulose and aminoalkyl methacrylate copolymer at a ratio of about 50/50 by wt., wherein the second taste-masking membrane is disposed on the first taste-masking membrane and the second taste-masking membranes has a thickness of from about 15% to about 30% by wt. of the taste-masked drug containing particle;
(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 orally disintegrating pharmaceutical composition 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 3 (depends on 1)

The orally disintegrating pharmaceutical composition 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 4 (depends on 1)

The orally disintegrating pharmaceutical composition of claim 1, wherein the ethylcellulose in the first taste-masking membrane has a viscosity of about 100 cps.

### Claim 5 (depends on 1)

The orally disintegrating pharmaceutical composition of claim 1, wherein the ethylcellulose in the second taste-masking membrane has a viscosity of about 10 cps.

### Claim 6 (depends on 1)

The orally disintegrating pharmaceutical composition of claim 1, wherein the ethylcellulose in the first taste-masking membrane has a viscosity of about 100 cps, and the ethylcellulose in the second taste-masking membrane has a viscosity of about 10 cps.

### Claim 7 (depends on 1)

The orally disintegrating pharmaceutical composition of claim 1, wherein the disintegrant and the sugar alcohol and/or saccharide are present together in the form of rapidly dispersing microgranules.

### Claim 8 (depends on 7)

The orally disintegrating pharmaceutical composition of claim 7, wherein the rapidly dispersing microgranules have an average particle size of not more than about 300 μm.

### Claim 9 (depends on 8)

The orally disintegrating pharmaceutical composition of claim 8, wherein the disintegrant has an average particle diameter of not more than about 30 μm.

### Claim 10 (depends on 8)

The orally disintegrating pharmaceutical composition of claim 8, wherein the sugar alcohol and/or saccharide has an average particle diameter of not more than about 30 μm.

### Claim 11 (depends on 1)

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

### Claim 12 (depends on 1)

The orally disintegrating pharmaceutical composition 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 13 (depends on 1)

The orally disintegrating pharmaceutical composition 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 14 (depends on 1)

The orally disintegrating pharmaceutical composition 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 15 (depends on 1)

The orally disintegrating pharmaceutical composition 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 16 (depends on 15)

The orally disintegrating pharmaceutical composition of claim 15, 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 17 (depends on 15)

The orally disintegrating pharmaceutical composition of claim 15, 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 18 (depends on 15)

The orally disintegrating pharmaceutical composition of claim 15, 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 19 (depends on 15)

The orally disintegrating pharmaceutical composition of claim 15, 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 20 (depends on 15)

The orally disintegrating pharmaceutical composition of claim 15, 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 21 (depends on 15)

The orally disintegrating pharmaceutical composition of claim 15, 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 22 (depends on 15)

The orally disintegrating pharmaceutical composition of claim 15, 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.