Short duration depot formulations

• US 8,278,330 B2
• Filed: 09/27/2010
• Issued: 10/02/2012
• Est. Priority Date: 06/25/2002
• Status: Expired due to Fees

• Current Assignee: DURECT Corporation
• Original Assignee: DURECT Corporation
• Inventors: Chen, Guohua, Priebe, David
• Primary Examiner(s): VU, JAKE MINH
• Application Number:
  US12/924,441
• Publication Number:
  US 20110046181A1
• Time in Patent Office: 736 Days
• Field of Search: 514/330
• US Class Current: 514/330
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• 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 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• 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 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 23/02 Local anaesthetics

Abstract

Methods and compositions for systemically or locally administering by implantation a beneficial agent to a subject are described, and include, for example, depot gel compositions that can be injected into a desired location and which can provide controlled release of a beneficial agent over a short duration of time. The compositions include a low molecular weight biocompatible polymer, a biocompatible solvent having low water miscibility that forms a viscous gel with the polymer and limits water uptake by the implant, and a beneficial agent.

Claims

1. A sustained release dosage form of an anesthetic, said dosage form comprising:

a short duration gel vehicle comprising a low molecular weight bioerodible, biocompatible polymer and a water-immiscible solvent in an amount effective to plasticize the polymer and form a gel therewith; and

an anesthetic dissolved or dispersed in the gel vehicle, wherein said polymer is a lactic acid-based polymer having a weight average molecular weight from about 3,000 to about 10,000, said solvent is benzyl alcohol, and said anesthetic is bupivacaine, and further wherein the dosage form provides for a reduced initial burst of the anesthetic from the dosage form after local administration.

2. The sustained release dosage form of claim 1, wherein the sustained release occurs in a period of less than or equal to about seven days.

3. The sustained release dosage form of claim 2, wherein the sustained release lasts for a period of between about 24 hours to about seven days.

4. The sustained release dosage form of claim 2, wherein the sustained release lasts for a period of about three days.

5. The sustained release dosage form of claim 1, wherein the polymer comprises a copolymer of lactic acid and glycolic acid (PLGA).

6. The sustained release dosage form of claim 5, wherein the copolymer has a monomer ratio of lactic acid to glycolic acid of approximately 50:

50.

7. The sustained release dosage form of claim 1, wherein the polymer has a weight average molecular weight of between about 3,000 and about 8,000.

8. The sustained release dosage form of claim 1, wherein the dosage form comprises from about 1% to about 30% anesthetic by weight.

9. The sustained release dosage form of claim 1, wherein the anesthetic comprises particles having an average particle size of less than about 250 μ

m.

10. The sustained release dosage form of claim 1, wherein the anesthetic comprises particles of bupivacaine base.