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

• US 7,048,946 B1
• Filed: 09/24/1998
• Issued: 05/23/2006
• Est. Priority Date: 06/02/1995
• Status: Expired due to Fees

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Inventors: Kochinke, Frank, Wong, Vernon
• Primary Examiner(s): Webman, Edward J.
• Application Number:
  US09/160,635
• Time in Patent Office: 2,798 Days
• Field of Search: 424/400, 424/486, 424/488, 424/499, 424/501, 424/426, 424/428, 424/443
• US Class Current: 424/486
• 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 controlled, sustained release for an extended period of time.

Claims

1. An implant for controlled, 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 first therapeutically active agent at a concentration from 10 to 50 weight percent of the implant;

a release modulator comprising hydroxy-propylmethylcellulose at a concentration from 10 to 50 weight percent of the implant, and said release modulator further comprising a second therapeutically active agent having a different activity than the first therapeutically active agent;

wherein said implant is an anhydrous solid structure which is degraded at the site of implantation and releases said first therapeutically active agent within a therapeutic dosage which does not vary by more than about 100% for a period of at least about 3 days after implantation;

wherein said anhydrous solid structure is a particle, sheet, plaque, fiber, microcapsule or disc.

2. An implant according to claim 1, wherein said first therapeutically active agent is a steroid and said second therapeutically active agent is a water soluble antibiotic.

3. An implant according to claim 1, wherein said first therapeutically active agent is a non-steroidal antiinflammatory drug and said second therapeutically active agent is a water soluble antibiotic.

4. An implant according to claim 1 wherein said biodegradable polymer is poly-lactic acid glycolic acid copolymer.

5. An implant for controlled, sustained drug release comprising:

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

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

a release modulator comprising hydroxy-propylmethylcellulose at a concentration from 10 to 50 weight percent of the implant said release modulator further comprising a second therapeutically active agent having a different activity than the antiinflammatory drug;

wherein said implant is an anhydrous solid structure which releases said therapeutically active antiinflammatory within a therapeutic dosage that does not vary by more than about 100% for a period of at least about 3 days.

6. An implant for controlled, sustained drug release comprising:

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

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

a release modulator comprising hydroxy-propylmethylcellulose at a concentration from 10 to 50 weight percent of the implant, and said release modulator further comprising a second therapeutically active agent having a different activity than the steroid;

wherein said implant is an anhydrous solid structure which is degraded at the site of implantation and releases said therapeutically active steroid within a therapeutic dosage which does not vary by more than about 100% for a period of at least about 3 days after implantation.

7. An implant according to claim 6, wherein said anhydrous solid structure is a particle, sheet, patch, plaque, fiber, microcapsule or disc.

8. An implant according to claim 6 wherein said second therapeutically active agent is a hydrophilic compound.

9. An implant according to claim 8 wherein said second therapeutically active agent is a water soluble antibiotic.

10. An implant for controlled, sustained drug release comprising:

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

a therapeutically active non-steroidal anti-inflammatory drug at a concentration from 10 to 50 weight percent of the implant;

a release modulator comprising hydroxy-propylmethylcellulose at a concentration from 10 to 50 weight percent of the implants and the release modulator further comprising a second therapeutically active agent having a different activity than the therapeutically active non-steroidal anti-inflammatory drug;

wherein said implant is an anhydrous solid structure which releases said therapeutically active non-steroidal anti-inflammatory drug within a therapeutic dosage which does not vary by more than about 100% for a period of at least about 3 days after implantation.

11. An implant according to claim 10, wherein said second therapeutically active agent is a hydrophilic compound.

12. An implant according to claim 11, wherein said second therapeutically active agent is a water soluble antibiotic.