# US 11,896,722 B2 · Methods and compositions particularly for treatment of attention deficit disorder

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- Number: US 11,896,722 B2
- Document ID: US11896722B2
- Status: Granted
- Kind: B2
- Application number: 17/647,149
- Filed: 2022-01-05
- Published: 2022-07-28
- Granted: 2024-02-13
- Earliest claimed: 2014-10-31
- Assignees: Purdue Pharma L.P.
- Applicants: Purdue Pharma L.P.
- Inventors: Ricardo Alberto Vargas Rincon; Joseph Reiz
- Web page: https://patentgrep.com/patent/US11896722B2

## CPC

- A61K 9/5078: {with drug-free core}
- 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 9/1676: {having a drug-free core with discrete complete coating layer containing drug (adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921)}
- A61K 9/48: Preparations in capsules, e.g. of gelatin, of chocolate {(A61K9/0004 takes precedence; bite capsules A61K9/0056)}
- A61K 9/5026: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/5036: {Polysaccharides, e.g. gums, alginate; Cyclodextrin}
- A61K 9/5084: {Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs (tablets containing such a mixture A61K9/2077)}
- A61K 31/4458: only substituted in position 2, e.g. methylphenidate
- A61K 47/06: Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/26: Psychostimulants, e.g. nicotine, cocaine
- 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

There is described, inter alia, a coated bead comprising: (a) a granule; (b) a first layer coated over the granule, the first layer comprising a first amount of an active pharmaceutical ingredient comprising a central nervous system stimulant; and (c) a second layer coated over the first layer, the second layer being present in an amount sufficient to substantially delay release of the active pharmaceutical ingredient in the first layer until after the coated bead reaches a distal intestine portion of a subject to whom the coated bead is administered; and (d) the third layer coated over the second layer, the third layer comprising a second amount of the active pharmaceutical ingredient, the third layer being configured to permit substantially immediate release of the active pharmaceutical ingredient comprised therein. Embodiments related to a solid oral pharmaceutical composition are also described.

## Claims

### Claim 1

A method of treating attention deficit hyperactivity disorder (ADHD) in a subject in need thereof, the method comprising orally administering to the subject a dosage form providing 25, 35, 45, 55, 70, 85, or 100 mg of methylphenidate hydrochloride, wherein the dosage form provides: a first in vivo methylphenidate Tmax and a second in vivo methylphenidate Tmax, wherein in a fed state, the second in vivo methylphenidate Tmax is a Tmax8-16 of about 13.5 hours; and efficacious treatment of ADHD for about 16 hours after a single oral administration, further wherein the dosage form has an in vitro methylphenidate hydrochloride dissolution rate that does not increase in the presence of about either 5% or 20% ethanol when measured under in vitro conditions with stirring at 100 rpm at pH 1.2 for 2 hours in 900 mL of a medium comprising up to about either 5% or 20% v/v ethanol.

### Claim 2 (depends on 1)

The method of claim 1, wherein not more than 20% of the methylphenidate hydrochloride in the dosage form is released after two hours when measured under in vitro conditions with stirring at 100 rpm at pH 1.2 for 2 hours in 900 mL of a medium comprising up to about 20% v/v ethanol.

### Claim 3 (depends on 1)

The method of claim 1, wherein not more than 20% of the methylphenidate hydrochloride in the dosage form is released after two hours when measured under in vitro conditions with stirring at 100 rpm at pH 1.2 for 2 hours in 900 mL of a medium comprising up to about 5% v/v ethanol.

### Claim 4 (depends on 1)

The method of claim 1, wherein the dosage form comprises an immediate release methylphenidate hydrochloride component and a controlled/delayed release methylphenidate hydrochloride component, wherein the immediate release methylphenidate hydrochloride component and the controlled/delayed release methylphenidate hydrochloride component, together, provide 25, 35, 45, 55, 70, 85, or 100 mg of methylphenidate hydrochloride.

### Claim 5 (depends on 4)

The method of claim 4, wherein the dosage form has the following in vitro methylphenidate dissolution profile:
Time (hours)
Methylphenidate (% dissolved)
1
NLT 15%
4
18-38%
8
35-55%
12
68-98
16
NLT 68
with 900 ml simulated gastric fluid for 2 hours, (ii) followed by 900 ml phosphate buffer pH 6.0 for 4 hours, and (iii) for the 7th hour onwards, 900 mL of phosphate buffer pH 7.4; USP<711> Acceptance Table 2.

### Claim 6 (depends on 4)

The method of claim 4, wherein the controlled/delayed release methylphenidate hydrochloride component and the immediate release methylphenidate hydrochloride component are provided via a plurality of coated beads.

### Claim 7 (depends on 6)

The method of claim 6, wherein each bead comprises a portion of the controlled/delayed release methylphenidate hydrochloride component and a portion of the immediate release methylphenidate hydrochloride component.

### Claim 8 (depends on 7)

The method of claim 7, wherein each bead in the plurality of beads comprises a core comprising a first amount of methylphenidate hydrochloride corresponding to the portion of the controlled/delayed release methylphenidate hydrochloride component.

### Claim 9 (depends on 8)

The method of claim 8, wherein the core comprises a granule coated with the first amount of methylphenidate hydrochloride or wherein the core comprises a granule substrate in admixture with the first amount of methylphenidate hydrochloride.

### Claim 10 (depends on 9)

The method of claim 9, wherein the first amount of methylphenidate hydrochloride is coated with an inner controlled release coating and an outer delayed release coating coated over the inner controlled release coating.

### Claim 11 (depends on 10)

The method of claim 10, wherein a second amount of methylphenidate hydrochloride, corresponding to the portion of the immediate release methylphenidate hydrochloride component, is coated over the outer delayed release coating.

### Claim 12 (depends on 11)

The method of claim 11, wherein the controlled/delayed release methylphenidate hydrochloride component comprises about 78 weight percent to about 82 weight percent of the 25, 35, 45, 55, 70, 85, or 100 mg of methylphenidate hydrochloride in the pharmaceutical composition.

### Claim 13 (depends on 12)

The method of claim 12, wherein the inner controlled release coating is present in an amount of about 3 percent to about 16 percent by weight of each bead in the plurality of coated beads, and wherein the outer delayed release coating is present in an amount of from about 3 percent to about 20 percent by weight of each bead in the plurality of coated beads.

### Claim 14 (depends on 13)

The method of claim 13, wherein the inner controlled release coating comprises ammonio methacrylate copolymer, Type B USP/NF.

### Claim 15 (depends on 14)

The method of claim 14, wherein the outer delayed release coating comprises poly(methyl acrylate-co-methyl methacrylate-co-methacrylic acid) 7:3:1.