Oil-in-oil emulsified polmeric implants containing a hypotensive lipid and related methods

Abstract

Biocompatible intraocular implants, such as microparticles, include a prostamide component and a biodegradable polymer that is effective in facilitating release of the prostamide component into an eye for an extended period of time. The prostamide component may be associated with a biodegradable polymer matrix, such as a matrix of a two biodegradable polymers. Or, the prostamide component may be encapsulated by the polymeric component. The present implants include oil-in-oil emulsified implants or microparticles. Methods of producing the present implants are also described. The implants may be placed in an eye to treat or reduce a at least one symptom of an ocular condition, such as glaucoma.

1 . An intraocular implant comprising therapeutic polymeric microparticles, the microparticles made by the steps of: encapsulating a prostaglandin analog with a polymeric component to form a population of prostaglandin analog-encapsulated microparticles by an oil-in-oil emulsion process, wherein the prostaglandin analog -encapsulated microparticles have an effective average particle size of less than about 3000 nanometers. 
     
     
         2 . The implant of  claim 1 , wherein the oil-in-oil emulsion process comprises forming an oil-in-oil emulsion containing the prostaglandin analog and the polymeric component; drying the emulsion to form a dried emulsion product; contacting the dried emulsion product with a solvent to form a solvent-containing composition; and removing the solvent from the solvent containing composition to form the population of microparticles comprising the prostaglandin analog and the polymeric component. 
     
     
         3 . The implant of  claim 1 , wherein the prostaglandin analog of the microparticles so produced is encapsulated by the polymeric component to preserve therapeutic activity of the prostaglandin analog after a terminal sterilization procedure. 
     
     
         4 . The implant of  claim 1 , wherein the polymeric component comprises a biodegradable polymer or biodegradable copolymer. 
     
     
         5 . The implant of  claim 1 , wherein the polymeric component comprises a poly(lactide-coglycolide) PLGA copolymer. 
     
     
         6 . The implant of  claim 5 , wherein the PLGA copolymer has a lactide/glycolide ratio of 75/25 a molecular weight of about 63 kilodaltons, and an inherent viscosity of about 0.6 dL/g. 
     
     
         7 . The implant of  claim 2 , further comprising forming a first composition comprising the prostaglandin analog, the polymeric component, and an organic solvent, and forming a second oil-containing composition, wherein the forming the oil-in-oil emulsion step comprises mixing the first composition and the second oil containing composition. 
     
     
         8 . The implant of  claim 2 , wherein the drying comprises evaporating the oil-in-oil emulsion to form an evaporated product. 
     
     
         9 . The implant of  claim 8 , further comprising suspending the evaporated product in the solvent before removing the solvent from the solvent-containing composition. 
     
     
         10 . The implant of  claim 1 , further comprising terminally sterilizing the polymeric microparticles.