Formulation for controlled release of drugs by combining hydrophilic and hydrophobic agents

• US 20030095995A1
• Filed: 12/20/2002
• Published: 05/22/2003
• Est. Priority Date: 06/02/1995
• Status: Abandoned Application

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Inventors: Wong, Vernon, Kochinke, Frank
• Application Number:
  US10/327,018
• Publication Number:
  US 20030095995A1
• Time in Patent Office: Days
• US Class Current: 424/426
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: 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
• CPC Class Codes: 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
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/204 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

Combinations of hydrophilic and hydrophobic entities in a biodegradable sustained release implant are shown to modulate each other'"'"'s rate of release. Formulations of a therapeutically active agent and modulator provide substantially constant rate of release for an extended period of time.

Claims

1. An implant for sustained drug release comprising:

a pharmacologically acceptable biodegradable polymer which is degraded at the site of implantation, wherein said biodegradable polymer comprises at least about 20 weight percent of the implant;

a therapeutically active agent at a concentration from 10 to 50 weight percent of the implant;

a release modulator at a concentration from 10 to 50 weight percent of the implant;

wherein said therapeutically active agent is released within a therapeutic dosage which does not vary by more than about 100% for a period of at least about 3 days.

2. An implant according to claim 1, wherein said release modulator is a hydrophilic entity and said therapeutically active agent is a hydrophobic entity.

3. An implant according to claim 2, wherein said release modulator is hydroxypropylmethylcellulose.

4. An implant according to claim 1, wherein said release modulator is a hydrophobic entity and said therapeutically active agent is a hydrophilic entity.

5. An implant according to claim 1, wherein said release modulator is a therapeutically active agent.

6. An implant according to claim 5, wherein said active agent is a steroid and said release modulator is a water soluble antibiotic.

7. An implant according to claim 5, wherein said active agent is a non-steroidal antiinflammatory drug and said release modulator is a water soluble antibiotic.

8. An amplant according to claim 1, wherein said biodegradable polymer is poly-lactate glycolic acid copolymer.

9. An implant for sustained drug release comprising:

poly-lactate glycolic acid copolymer at a concentration of at least about 20 weight percent of the implant;

methotrexate at a concentration from 10 to 50 weight percent of the implant;

ciprofloxin at a concentration from 10 to 50 weight percent of the implant;

wherein said methotrexate is released within a therapeutic dosage which does not vary by more than about 100% for a period of at least about 3 days.