# US 2016/0243109 A1 · Encased Tamper Resistant Controlled Release Dosage Forms

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- Number: US 2016/0243109 A1
- Document ID: US20160243109A1
- Status: Published application
- Kind: A1
- Application number: 15/045,975
- Filed: 2016-02-17
- Published: 2016-08-25
- Earliest claimed: 2010-12-22
- Assignees: Purdue Pharma L.P.
- Applicants: Purdue Pharma L.P.
- Inventors: Haiyong Hugh Huang
- Web page: https://patentgrep.com/patent/US20160243109A1

## CPC

- A61K 9/2077: {Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets}
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/2031: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/2086: {Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat (active cores with a complete drug-free outer coat A61K9/28)}
- A61K 9/209: {containing drug in at least two layers or in the core and in at least one outer layer}
- A61K 9/28: Dragees; Coated pills or tablets {, e.g. with film or compression coating (A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209)}
- A61K 31/485: Morphinan derivatives, e.g. morphine, codeine
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- 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

In certain embodiments, the present invention is directed to a solid controlled release dosage form comprising: a core comprising a first portion of an opioid analgesic dispersed in a first matrix material; and a shell encasing the core and comprising a second portion of the opioid analgesic dispersed in a second matrix material; wherein the amount of opioid analgesic released from the dosage form is proportional within 20% to elapsed time from 8 to 24 hours, as measured by an in-vitro dissolution in a USP Apparatus 1 (basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37 C.

## Claims

### Claim at position 1

1-136. (canceled)

### Claim 137

A solid controlled release dosage form comprising:
a core comprising a first portion of hydrocodone or a pharmaceutically acceptable salt thereof dispersed in a first matrix material; and
a shell encasing the core and comprising a second portion of the hydrocodone or pharmaceutically acceptable salt thereof dispersed in a second matrix material;
wherein the amount of hydrocodone or pharmaceutically acceptable salt thereof released from the dosage form, as measured by an in-vitro dissolution in a USP Apparatus 1 (basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37° C., at 2 hours, is less than about 25%; at 4 hours, is from about 10% to about 30%; at 8 hours, is from about 20% to about 60%; at 12 hours, is from about 40% to about 90%; and at 18 hours, is greater than about 70%; and
wherein the dosage form can be flattened without breaking, wherein the thickness of the dosage form after flattening corresponds to no more than about 20% of the thickness of the dosage form before flattening; and
the amount of hydrocodone or salt thereof released at 0.5 hour from a flattened dosage form deviates no more than about 20% points from a non-flattened dosage form as measured by an in-vitro dissolution in a USP Apparatus 1 (basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37° C.

### Claim 138 (depends on 137)

The solid controlled release dosage form of claim 137, wherein the first matrix material, the second matrix material, or both the first and second matrix material comprises polyethylene oxide.

### Claim 139 (depends on 138)

The solid controlled release dosage form of claim 138, wherein the polyethylene oxide has an average molecular weight from about 300,000 to about 10,000,000.

### Claim 140 (depends on 138)

The solid controlled release dosage form of claim 138, wherein the polyethylene oxide has an average molecular weight from about 1,000,000 to about 10,000,000.

### Claim 141 (depends on 138)

The solid controlled release dosage form of claim 138, wherein the first matrix material, the second matrix material, or both the first and second matrix material comprises a cellulose ether.

### Claim 142 (depends on 141)

The solid controlled release dosage form of claim 141, wherein the first matrix material, the second matrix material, or both the first and second matrix material comprises a hydroxyalkylcellulose.

### Claim 143 (depends on 142)

The solid controlled release dosage form of claim 142, wherein the hydroxyalkylcellulose is hydroxypropylcellulose

### Claim 144 (depends on 141)

The solid controlled release dosage form of claim 141, wherein the first matrix material, the second matrix material, or both the first and second matrix material comprises microcrystalline cellulose.

### Claim 145 (depends on 144)

The solid controlled release dosage form of claim 144, comprising a compressed dispersion of the hydrocodone or pharmaceutically acceptable salt thereof and the matrix material.

### Claim 146 (depends on 144)

The solid controlled release dosage form of claim 144, comprising granules comprising the hydrocodone or pharmaceutically acceptable salt thereof and the first matrix material.

### Claim 147 (depends on 146)

The solid controlled release dosage form of claim 146, wherein the granules are compressed into a tablet.

### Claim 148 (depends on 144)

The solid controlled release dosage form of claim 144, wherein the hydrocodone or pharmaceutically acceptable salt thereof is hydrocodone bitartrate.

### Claim 149 (depends on 148)

The solid controlled release dosage form of claim 148, wherein the total amount of hydrocodone bitartrate in the dosage form is from about 0.5 mg to about 1250 mg.

### Claim 150 (depends on 144)

The solid controlled release dosage form of claim 144, which provides a C24/Cmax ratio of hydrocodone of about 0.55 to about 1.0 after oral administration to a subject.

### Claim 151 (depends on 144)

The solid controlled release dosage form of claim 144, which provides a Tmax (h) of hydrocodone from about 4 to about 20 hours after oral administration to a subject.

### Claim 152 (depends on 150)

The solid controlled release dosage form of claim 150, wherein the administration is a first administration to a population of subjects.

### Claim 153 (depends on 150)

The solid controlled release dosage form of claim 150, wherein the administration is steady state administration to a subject.

### Claim 154 (depends on 144)

The solid controlled release dosage form of claim 144, which contains about 20 mg hydrocodone or a pharmaceutically acceptable salt thereof.

### Claim 155 (depends on 144)

The solid controlled release dosage form of claim 144, which contains about 120 mg hydrocodone or a pharmaceutically acceptable salt thereof.

### Claim 156 (depends on 144)

The solid controlled release dosage form of claim 144, which provides a mean AUC (ng*h/mL) after oral administration to a subject of about 250 to 400 per each 20 mg hydrocodone or pharmaceutically acceptable salt thereof included in the dosage form.

### Claim 157 (depends on 144)

The solid controlled release dosage form of claim 144, which provides a mean Cmax (ng/mL) after oral administration to a subject of about 10 to about 30 per each 20 mg hydrocodone or pharmaceutically acceptable salt thereof included in the dosage form.

### Claim 158 (depends on 144)

The solid controlled release dosage form of claim 144, which provides a mean Tmax (h) after oral administration to a subject of about 10 to about 20.

### Claim 159 (depends on 144)

The solid controlled release dosage form of claim 144, which provides a mean T1/2 (h) after oral administration to a subject of about 5 to about 10.

### Claim 160 (depends on 144)

The solid controlled release dosage form of claim 144, which provides a mean Tlag (h) after oral administration to a subject of about 0.01 to about 0.2.

### Claim 161 (depends on 144)

The solid controlled release dosage form of claim 144, wherein the mean C24/Cmax ratio is about 0.2 to about 0.8 after oral administration to a subject.

### Claim 162 (depends on 161)

The solid controlled release dosage form of claim 161, wherein the administration is in the fasted state.

### Claim 163 (depends on 144)

The solid controlled release dosage form of claim 144, wherein the mean AUC (ng*h/mL) after oral administration to a subject in the fed state is less than 20% higher than the AUC (ng*h/mL) after oral administration to a subject in the fasted state.

### Claim 164 (depends on 144)

The solid controlled release dosage form of claim 144, wherein the mean Cmax (ng/mL) after oral administration to a subject in the fed state is less than 80% higher than the Cmax after oral administration to a subject in the fasted state.

### Claim 165 (depends on 144)

The solid controlled release dosage form of claim 144, wherein the mean Tmax (h) after oral administration to a subject in the fed state is within 25% of the Tmax (h) after oral administration to a subject in the fasted state.

### Claim 166 (depends on 144)

The solid controlled release dosage form of claim 144, wherein the mean T1/2 (h) after oral administration to a subject in the fed state is within 8% of the T1/2 after oral administration to a subject in the fasted state.