Low temperature processes for making cyclic lipid implants for intraocular use

• US 8,846,073 B2
• Filed: 12/19/2006
• Issued: 09/30/2014
• Est. Priority Date: 12/19/2006
• Status: Active Grant

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Inventors: Spada, Lon T., Chang, James N., Luu, Michelle
• Primary Examiner(s): Huang, Gigi
• Application Number:
  US11/612,928
• Publication Number:
  US 20080145403A1
• Time in Patent Office: 2,842 Days
• Field of Search: 424/428
• US Class Current: 424/428
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• 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 47/34 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 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/141 Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers (co) spray-dried products A61K9/16, (co) lyophilised products A61K9/19; the carrier being chemically bound to the active ingredient A61K47/50
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/10 for accommodation disorders, e.g. myopia
• CPC Class Codes: A61P 27/12 for cataracts
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals

Abstract

Biocompatible implants comprising a cyclic lipid therapeutic agent are made using a low temperature melt extrusion process. The implants are suitable for intraocular use to treat an ocular condition.

Claims

1. A low temperature process for making an intraocular implant, the process comprising the steps of:

(a) combining a cyclic lipid therapeutic agent, a polymer, and a low melting cosolvent to form a mixture;

wherein the solubility parameters of the cyclic lipid therapeutic agent, the polymer, and the low melting cosolvent are all within about 10 Mpa^1/2 of each other;

wherein the low melting cosolvent has a melt temperature of between about 50°

C. and about 80°

C.;

wherein the cyclic lipid therapeutic agent is selected from the group consisting of bimatoprost, latanoprost, travoprost, unoprostone, prostaglandin E1, prostaglandin E2, and mixtures thereof;

wherein the polymer is a biodegradable polymer selected from the group consisting of polylactic acid, polyglycolic acid, and polylactide-co-glycolide; and

wherein the low melting cosolvent is selected from the group consisting of decafluorobutane, poly(hexamethylene adipamide), and polyethylene glycol 3350;

(b) heating the mixture to a temperature between about 50°

C. and about 80°

C., and;

(c) extruding the heated mixture, thereby making an implant suitable for intraocular use, wherein the cyclic lipid therapeutic agent comprises 20% by weight of the intraocular implant, and wherein the potency of the cyclic lipid therapeutic agent released from the implant is at least about 50% of its maximum potency.

2. The process of claim 1 wherein the cyclic lipid therapeutic agent is bimatoprost.

3. The process of claim 2, wherein the low melting cosolvent is polyethylene glycol 3350, wherein the polymer is a polylactide-co-glycolide, wherein the cyclic lipid therapeutic agent is bimatoprost, and wherein the mixture is extruded at a temperature of 65°

C.

4. The process of claim 1, wherein the low melting cosolvent is decafluorobutane.

5. The process of claim 1, wherein the low melting cosolvent is poly(hexamethylene adipamide).