# US 2013/0280331 A1 · Depot Compositions with multiple drug release rate controls and uses thereof

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- Number: US 2013/0280331 A1
- Document ID: US20130280331A1
- Status: Published application
- Kind: A1
- Application number: 13/766,662
- Filed: 2013-02-13
- Published: 2013-10-24
- Earliest claimed: 2001-11-14
- Assignees: Durect Corporation
- Applicants: Durect Corporation
- Inventors: Guohua Chen; Paul R. Houston; Lothar W. Kleiner; Jeremy Corwin Wright
- Web page: https://patentgrep.com/patent/US20130280331A1

## CPC

- A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- A61K 9/0024: {Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L)}
- A61K 9/143: {with inorganic compounds}
- A61K 9/145: {with organic compounds}
- A61K 9/146: {with organic macromolecular compounds}
- A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)}
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- 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

Injectable depot compositions with dual mechanisms of release rate control are provided for sustained beneficial agent delivery in a patient. The composition includes bioerodible particles and an injectable depot vehicle containing a bioerodible polymer in an organic solvent, for forming a bioerodible depot implant after administration to the patient. The bioerodible particles are dispersed in the depot vehicle and contain a beneficial agent and a release rate controlling agent retarding the release of the beneficial agent from the bioerodible particles and from the depot implant.

## Claims

### Claim at position 1

-41. (canceled)

### Claim 42

A composition comprising:
a gel comprising:
approximately 5 wt % to approximately 90 wt % of a biodegradable, biocompatible lactic acid-based polymer having a weight average molecular weight ranging from approximately 1000 to approximately 30,000;
an ester of an aromatic acid, said ester having miscibility in water of less than or equal to 7% at 25° C.;
an aromatic alcohol having miscibility in water of less than or equal to 7% at 25° C., wherein the aromatic alcohol has the structural formula (I)
Ar-(L)n-OH (I)
in which Ar is a substituted or unsubstituted aryl or heteroaryl group, n is zero or 1, and L is a linking moiety; and
particles comprising beneficial agent suspended in the gel, the particles having an average particle size ranging from 0.1 micron to 250 microns,
wherein the composition is free of monohydric C1 to C6 alkanol.

### Claim 43 (depends on 42)

The composition of claim 42, wherein the lactic acid-based polymer is present in an amount ranging from about 5 wt % to about 35 wt % of the composition.

### Claim 44 (depends on 42)

The composition of claim 42, wherein the lactic acid-based polymer is present in an amount ranging from about 5 wt % to about 25 wt % of the composition.

### Claim 45 (depends on 42)

The composition of claim 42, wherein the lactic acid-based polymer comprises a copolymer of lactic acid and glycolic acid.

### Claim 46 (depends on 42)

The composition of claim 42, wherein the lactic acid-based polymer has a monomer ratio of lactic acid to glycolic acid ranging from 100:0 to 30:70.

### Claim 47 (depends on 42)

The composition of claim 42, wherein the ester of an aromatic acid is a lower alkyl ester or an aralkyl ester of benzoic acid.

### Claim 48 (depends on 42)

The composition of claim 42, wherein the ester of an aromatic acid comprises a member selected from methyl benzoate, ethyl benzoate, n-propyl benzoate, isopropyl benzoate, butyl benzoate, isobutyl benzoate, sec-butyl benzoate, tert-butyl benzoate, isoamyl benzoate, and benzyl benzoate.

### Claim 49 (depends on 42)

The composition of claim 42, wherein the ester of an aromatic acid comprises benzyl benzoate.

### Claim 50 (depends on 42)

The composition of claim 42, wherein the aromatic alcohol comprises benzyl alcohol.

### Claim 51 (depends on 42)

The composition of claim 42, wherein the aromatic alcohol has miscibility in water of less than or equal to 5 wt % at 25° C.

### Claim 52 (depends on 42)

The composition of claim 42, wherein the composition is free of solvents having miscibility in water that is greater than 7 wt % at 25° C.

### Claim 53 (depends on 42)

The composition of claim 42, wherein the ratio of the aromatic alcohol to the ester of an aromatic acid ranges from about 1% to about 99% by weight.

### Claim 54 (depends on 42)

The composition of claim 42, wherein the aromatic alcohol comprises benzyl alcohol, the ester of an aromatic acid comprises benzyl benzoate, and the ratio of the benzyl alcohol to the benzyl benzoate ranges from about 10% to about 50% by weight.

### Claim 55 (depends on 42)

The method of claim 42, wherein the beneficial agent is selected from a drug, protein, and peptide.

### Claim 56 (depends on 42)

The composition of claim 42, wherein the beneficial agent is present in an amount ranging from 0.1 wt % to 50 wt % of the composition.

### Claim 57 (depends on 56)

The composition of claim 56, wherein the composition is free of solvent having a miscibility in water that is greater than 7 wt % at 25° C.

### Claim 58 (depends on 42)

The composition of claim 42, wherein
the lactic acid-based polymer is present in the composition in an amount ranging from about 5 wt % to about 25 wt % of the composition,
the lactic acid-based polymer comprises a copolymer of lactic acid and glycolic acid,
the ester of an aromatic acid comprises benzyl benzoate,
the aromatic alcohol comprises benzyl alcohol,
the ratio of the benzyl alcohol to the benzyl benzoate ranges from about 10% to about 50% by weight, and
the beneficial agent is present in an amount ranging from 0.1 wt % to 50 wt % of the composition.

### Claim 59 (depends on 58)

The composition of claim 58, wherein the composition is free of solvent having a miscibility in water that is greater than 7 wt % at 25° C.