# US 10,441,657 B2 · Methods and compositions for self-regulated release of active pharmaceutical ingredient

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- Number: US 10,441,657 B2
- Document ID: US10441657B2
- Status: Granted
- Kind: B2
- Application number: 15/588,982
- Filed: 2017-05-08
- Published: 2017-08-24
- Granted: 2019-10-15
- Earliest claimed: 2012-11-30
- Assignees: Abuse Deterrent Pharmaceuticals, LLC
- Applicants: Acura Pharmaceuticals, Inc.
- Inventors: Albert W. Brzeczko; R. Gary Hollenbeck
- Web page: https://patentgrep.com/patent/US10441657B2

## CPC

- A61K 47/02: Inorganic compounds
- A61K 9/2009: {Inorganic compounds}
- A61K 9/2027: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/2077: {Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets}
- A61K 31/5517: condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
- 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 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/20: Hypnotics; Sedatives
- A61P 25/22: Anxiolytics
- A61P 25/26: Psychostimulants, e.g. nicotine, cocaine
- A61P 25/30: for treating abuse or dependence
- A61P 25/36: Opioid-abuse
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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

An abuse deterrent pharmaceutical composition including a pharmaceutically active ingredient; an acid soluble ingredient; and a buffering ingredient; wherein the acid soluble ingredient and the buffering ingredient retard release of the active pharmaceutical ingredient when the composition is ingested in excess of an intended dosage.

## Claims

### Claim 1

An abuse deterrent pharmaceutical composition comprising a unit dose, the unit dose comprising:
a particle portion, wherein the particle portion comprises:
a. a pharmaceutically active ingredient;
b. an acid soluble ingredient comprising a cationic copolymer based on methyl methacrylate; and
c. magnesium hydroxide; and
a pH modifying ingredient,
wherein the pH modifying ingredient is present in an amount sufficient to inhibit dissolution of the particle portion when three unit doses or greater of the abuse deterrent pharmaceutical composition is ingested, and
wherein the acid soluble ingredient and the pH modifying ingredient retard release of the pharmaceutically active ingredient when the three unit doses or greater of the composition is ingested.

### Claim 2 (depends on 1)

The abuse deterrent pharmaceutical composition of claim 1, wherein the pH modifying ingredient is present in an amount sufficient to raise the gastrointestinal pH to greater than about 4 when the three unit doses or greater of the abuse deterrent pharmaceutical composition is ingested.

### Claim 3 (depends on 1)

The abuse deterrent pharmaceutical composition of claim 1, wherein the pharmaceutically active ingredient comprises a drug susceptible to abuse.

### Claim 4 (depends on 3)

The abuse deterrent pharmaceutical composition of claim 3, wherein the drug susceptible to abuse comprises an opioid, a stimulant, and/or a sedative.

### Claim 5 (depends on 4)

The abuse deterrent pharmaceutical composition of claim 4, wherein the drug susceptible to abuse comprises an opioid selected from hydrocodone, hydromorphone, morphine, oxycodone, and/or salts thereof.

### Claim 6 (depends on 1)

The abuse deterrent pharmaceutical composition of claim 1, wherein the cationic copolymer is based on dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate.

### Claim 7 (depends on 1)

The abuse deterrent pharmaceutical composition of claim 1, further comprising a disintegrant.

### Claim 8 (depends on 7)

The abuse deterrent pharmaceutical composition of claim 7, wherein the disintegrant comprises sodium starch glycolate.

### Claim 9 (depends on 1)

The abuse deterrent pharmaceutical composition of claim 1, further comprising a lubricant.

### Claim 10 (depends on 9)

The abuse deterrent pharmaceutical composition of claim 9, wherein the lubricant comprises one or more of stearic acid, magnesium stearate, hydrogenated oil, sodium stearyl fumarate, and polyethylene glycol.

### Claim 11 (depends on 1)

The abuse deterrent pharmaceutical composition of claim 1, wherein the cationic copolymer is soluble in acid and insoluble above pH 5.

### Claim 12 (depends on 1)

The abuse deterrent composition of claim 1, wherein the unit dose is a capsule.

### Claim 13 (depends on 1)

The abuse deterrent composition of claim 1, wherein the unit dose is a tablet.

### Claim 14 (depends on 1)

The abuse deterrent composition of claim 1, wherein the acid soluble ingredient sequesters the pharmaceutically active ingredient from the pH modifying ingredient.

### Claim 15 (depends on 14)

The abuse deterrent composition of claim 14, wherein the acid soluble ingredient sequesters the pharmaceutically active ingredient from the pH modifying ingredient by coating the pharmaceutically active ingredient.

### Claim 16

An abuse deterrent pharmaceutical composition comprising a unit dose, the unit dose comprising:
a particle portion, wherein the particle portion comprises:
a. a pharmaceutically active ingredient;
b. an acid soluble ingredient comprising one or more of calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, and magnesium hydroxide; and
c. a buffering ingredient; and
a pH modifying ingredient,
wherein the pH modifying ingredient is present in an amount sufficient to inhibit dissolution of the particle portion when three unit doses or greater of the abuse deterrent pharmaceutical composition is ingested, and
wherein the acid soluble ingredient and the pH modifying ingredient retard release of the pharmaceutically active ingredient when the three unit doses or greater of the composition is ingested.

### Claim 17 (depends on 16)

The abuse deterrent pharmaceutical composition of claim 16, wherein the pH modifying ingredient is present in an amount sufficient to raise the gastrointestinal pH to greater than about 4 when the three unit doses or greater of the abuse deterrent pharmaceutical composition is ingested.

### Claim 18 (depends on 16)

The abuse deterrent pharmaceutical composition of claim 16, wherein the pharmaceutically active ingredient comprises a drug susceptible to abuse.

### Claim 19 (depends on 18)

The abuse deterrent pharmaceutical composition of claim 18, wherein the drug susceptible to abuse comprises an opioid, a stimulant, and/or a sedative.

### Claim 20 (depends on 19)

The abuse deterrent pharmaceutical composition of claim 19, wherein the drug susceptible to abuse comprises an opioid selected from hydrocodone, hydromorphone, morphine, oxycodone, and/or salts thereof.

### Claim 21 (depends on 16)

The abuse deterrent pharmaceutical composition of claim 16, wherein the acid soluble ingredient and the pH modifying ingredient are the same ingredient.

### Claim 22 (depends on 16)

The abuse deterrent pharmaceutical composition of claim 16, wherein the pH modifying ingredient comprises one or more of aluminum hydroxide, bismuth aluminate, bismuth carbonate, bismuth subcarbonate, bismuth subgallate, bismuth subnitrate, calcium carbonate, calcium phosphate, dibasic calcium phosphate, tribasic sodium phosphate, dihydroxyaluminum aminoacetate, dihydroxyaluminum sodium carbonate, glycine, magnesium glycinate, magnesium hydroxide, magnesium oxide, potassium bicarbonate, sodium bicarbonate, sodium potassium tartrate, tricalcium phosphate, and magnesium hydroxide.

### Claim 23 (depends on 16)

The abuse deterrent pharmaceutical composition of claim 16, further comprising a disintegrant.

### Claim 24 (depends on 23)

The abuse deterrent pharmaceutical composition of claim 23, wherein the disintegrant comprises sodium starch glycolate.

### Claim 25 (depends on 16)

The abuse deterrent pharmaceutical composition of claim 16, further comprising a lubricant.

### Claim 26 (depends on 25)

The abuse deterrent pharmaceutical composition of claim 25, wherein the lubricant comprises one or more of stearic acid, magnesium stearate, hydrogenated oil, sodium stearyl fumarate, and polyethylene glycol.

### Claim 27 (depends on 16)

The abuse deterrent pharmaceutical composition of claim 16, further comprising a cationic copolymer comprising dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate.

### Claim 28 (depends on 27)

The abuse deterrent pharmaceutical composition of claim 27, wherein the cationic copolymer is soluble in acid and insoluble above pH 5.

### Claim 29 (depends on 16)

The abuse deterrent pharmaceutical composition of claim 16, wherein the unit dose is a capsule.

### Claim 30 (depends on 16)

The abuse deterrent pharmaceutical composition of claim 16, wherein the unit dose is a tablet.

### Claim 31 (depends on 16)

The abuse deterrent pharmaceutical composition of claim 16, wherein the acid soluble ingredient sequesters the pharmaceutically active ingredient from the pH modifying ingredient.

### Claim 32 (depends on 31)

The abuse deterrent pharmaceutical composition of claim 31, wherein the acid soluble ingredient sequesters the pharmaceutically active ingredient from the pH modifying ingredient by coating the pharmaceutically active ingredient.

### Claim 33 (depends on 16)

The abuse deterrent pharmaceutical composition of claim 16, wherein the particle portion is sequestered by from the pH modifying ingredient by a polymeric coating comprising a copolymer based on methyl methacrylate.

### Claim 34 (depends on 16)

The abuse deterrent pharmaceutical composition of claim 16, wherein the particle portion further comprises a cationic copolymer.

### Claim 35 (depends on 34)

The abuse deterrent pharmaceutical composition of claim 34, wherein the cationic copolymer comprises a methyl methacrylate copolymer.

### Claim 36

An abuse deterrent pharmaceutical composition comprising an immediate release unit dose, the immediate release unit dose comprising:
a. a pharmaceutically active ingredient;
b. an acid soluble ingredient comprising a cationic polymer; and
c. a buffering ingredient,
wherein the buffering ingredient is in an amount sufficient to increase the gastric pH above 4 and the release of the active ingredient is retarded when at least 3 unit doses are ingested.

### Claim 37 (depends on 36)

The abuse deterrent pharmaceutical composition of claim 36, wherein the pharmaceutically active ingredient comprises a drug susceptible to abuse.

### Claim 38 (depends on 37)

The abuse deterrent pharmaceutical composition of claim 37, wherein the drug susceptible to abuse comprises an opioid, a stimulant, and/or a sedative.

### Claim 39 (depends on 38)

The abuse deterrent pharmaceutical composition of claim 38, wherein the drug susceptible to abuse comprises an opioid selected from hydrocodone, hydromorphone, morphine, oxycodone, and/or salts thereof.

### Claim 40 (depends on 36)

The abuse deterrent pharmaceutical composition of claim 36, wherein the cationic copolymer is based on dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate.

### Claim 41 (depends on 36)

The abuse deterrent pharmaceutical composition of claim 36, wherein the pH modifying ingredient comprises one or more of aluminum hydroxide, bismuth aluminate, bismuth carbonate, bismuth subcarbonate, bismuth subgallate, bismuth subnitrate, calcium carbonate, calcium phosphate, dibasic calcium phosphate, tribasic sodium phosphate, dihydroxyaluminum aminoacetate, dihydroxyaluminum sodium carbonate, glycine, magnesium glycinate, magnesium hydroxide, magnesium oxide, potassium bicarbonate, sodium bicarbonate, sodium potassium tartrate, tricalcium phosphate, and magnesium hydroxide.

### Claim 42 (depends on 36)

The abuse deterrent pharmaceutical composition of claim 36, further comprising a disintegrant.

### Claim 43 (depends on 42)

The abuse deterrent pharmaceutical composition of claim 42, wherein the disintegrant comprises sodium starch glycolate.

### Claim 44 (depends on 36)

The abuse deterrent pharmaceutical composition of claim 36, further comprising a lubricant.

### Claim 45 (depends on 44)

The abuse deterrent pharmaceutical composition of claim 44, wherein the lubricant comprises one or more of stearic acid, magnesium stearate, hydrogenated oil, sodium stearyl fumarate, and polyethylene glycol.

### Claim 46 (depends on 36)

The abuse deterrent pharmaceutical composition of claim 36, wherein the cationic copolymer is soluble in acid and insoluble above pH 5.