# US 8,465,759 B2 · Process for the preparation of a hot-melt extruded laminate

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 8,465,759 B2
- Document ID: US8465759B2
- Status: Granted
- Kind: B2
- Application number: 12/294,372
- Filed: 2007-03-22
- Published: 2009-05-28
- Granted: 2013-06-18
- Earliest claimed: 2006-03-24
- Assignees: Auxilium US Holdings, LLC
- Applicants: Michael M. Crowley; Justin M. Keen; John J. Koleng; Feng Zhang
- Inventors: Michael M. Crowley; Justin M. Keen; John J. Koleng; Feng Zhang
- Web page: https://patentgrep.com/patent/US8465759B2

## CPC

- A61K 9/7007: {Drug-containing films, membranes or sheets (A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence)}
- A61K 9/006: {Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays}
- B29C 48/07: Flat, e.g. panels
- B29C 48/08: flexible, e.g. films
- B29C 48/21: the layers being joined at their surfaces
- B29C 48/2556: {provided in or in the proximity of dies (B29C48/302, B29C48/31, B29C48/325 take precedence)}
- B29C 48/307: {specially adapted for bringing together components, e.g. melts within the die}
- B29C 48/31: {being} adjustable {, i.e. having adjustable exit sections}
- A61K 9/7069: {obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide}
- B29K 2105/0097: {Glues or adhesives, e.g. hot melts or thermofusible adhesives}
- B29K 2995/0092: hydrophilic
- B29K 2995/0093: hydrophobic
- 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)
- B29C: SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING (making preforms B29B11/00; making laminated products by combining previously unconnected layers which become one product whose layers will remain together B32B37/00 - B32B41/00)
- B29K: INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR {MOULDS, } REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS

## Abstract

A process for the preparation of a bioadhesive laminate comprising a hot-melt extruded reservoir layer and a hot-melt extruded backing layer is provided. The reservoir layer comprises a thermoplastic bioadhesive composition containing an active agent. An active agent-containing thermoplastic bioadhesive hydrophilic composition is hot-melt coextruded with a hydrophobic composition to form at least a bi-layered laminate. The hydrophilic composition and the hydrophobic composition have at least one polymer in common. In addition, the melt flow index of the hydrophobic composition is within 50% of the melt flow index of the hydrophilic composition. As a result, the laminate has a uniform transverse cross-section and/or a uniform longitudinal cross-section throughout a major of the length of the laminate. Moreover, when the laminate is divided into unit doses of approximately the same size, they have a high degree of content uniformity with respect to the active agent(s) present therein.

## Claims

### Claim 1

A bioadhesive bi-layered hot-melt extruded laminate comprising a hydrophilic bioadhesive reservoir layer and a hydrophobic backing layer, wherein
a) the bioadhesive reservoir layer comprises an active agent;
b) each of the bioadhesive reservoir layer and the backing layer comprises poly(ethylene) oxide (PEO); and
c) the backing layer comprises a hydrophilic polymer in a sufficiently low amount such that the backing layer is hydrophobic,
wherein the PEO in each layer is selected from the group consisting of PEO Grade 1, PEO Grade 2, PEO Grade 3, and a combination thereof, wherein: PEO Grade 1 is polyethylene oxide with (i) a solution viscosity in the range of 12-8800 mPa·s at 25° C. in a 5% solution, or (ii) an approximate molecular weight range from 100,000-600,000; PEO Grade 2 is polyethylene oxide with (i) a solution viscosity in the range of 8800 mPa·S at 25° C. in a 5% solution to 4000 mPa·s at 25° C. in a 2% solution, or (ii) an approximate molecular weight range from 900,000-2,000,000; and PEO Grade 3 is polyethylene oxide with (i) a solution viscosity in the range of 1650-15,000 mPa-s at 25° C. in a 1% solution, or (ii) an approximate molecular weight range from 4,000,000-8,000,000,
wherein the PEO in the bioadhesive reservoir layer comprises PEO Grade 1, PEO Grade 2, and PEO Grade 3.

### Claim 2 (depends on 1)

The laminate of claim 1, wherein the backing layer comprises two or more hydrophobic polymers.

### Claim 3 (depends on 1)

The laminate of claim 1, wherein the melt flow index of the reservoir layer is within 50% of the melt flow index of the backing layer.

### Claim 4 (depends on 1)

The laminate of claim 1, wherein the laminate comprises a controlled, sustained, slow, extended, or targeted release therapeutic composition.

### Claim 5 (depends on 1)

The laminate of claim 1, wherein the laminate comprises a dosage form adapted for transdermal, transmucosal, rectal, pulmonary, nasal, vaginal, ocular, or otic drug delivery, or as an implantable drug delivery device.

### Claim 6 (depends on 1)

The laminate of claim 1, wherein the active agent is selected from the group consisting of testosterone, oxybutynin, morphine, fentanyl, aspirin, lansoprazole, omeprazole, pantoprazole, rabeprazole and naltrexone.

### Claim 7 (depends on 1)

The laminate of claim 1, wherein each of the backing layer and the reservoir layer comprises at least 10% wt. of the PEO.

### Claim 8 (depends on 1)

The laminate of claim 1 further comprising a release liner layer removably affixed to the reservoir layer.

### Claim 9 (depends on 1)

The laminate of claim 1, wherein the reservoir layer comprises 40 to 90% by wt. of the laminate.

### Claim 10 (depends on 1)

The laminate of claim 1, wherein the active agent is fentanyl.

### Claim 11 (depends on 1)

The laminate of claim 1, wherein the active agent is testosterone.

### Claim 12 (depends on 1)

The laminate of claim 1, wherein the bioadhesive reservoir layer further comprises an acidic component.

### Claim 13 (depends on 1)

The laminate of claim 1, wherein the PEO in the backing layer comprises two or more grades of PEO selected from the group consisting of PEO Grade 1, PEO Grade 2, and PEO Grade 3.

### Claim 14 (depends on 1)

The laminate of claim 1, wherein the reservoir layer comprises about 10% to about 70% wt. of the PEO.

### Claim 15 (depends on 1)

A unit dose comprising a portion of a laminate according to claim 1, wherein the reservoir layer has an average exposed surface area between 90 and 250 mm2.

### Claim 16 (depends on 15)

The unit dose of claim 15 comprising a surface area to dose ratio of 5 to 35 mm2/mg active agent based upon the exposed surface of the reservoir layer.