Patent ID: 8445027

Claim:
A method for producing therapeutic polymeric microparticles, comprising encapsulating a prostamide component with a polymeric component to form a population of prostamide-encapsulated microparticles by an oil-in-oil emulsion process, wherein the polymeric component comprises a poly(lactide-co-glycolide) (PLGA) copolymer, the oil-in-oil emulsion process comprising: forming a first composition comprising a prostamide component, a poly(lactide-co-glycolide) (PLGA) copolymer, and an organic solvent; forming a second oil-containing composition; mixing the first composition and the second oil-containing composition to form an oil-in-oil emulsion; drying the emulsion to form a dried emulsion product; contacting the dried emulsion product with a solvent to form a solvent-containing composition; removing the solvent from the solvent-containing composition to form a population of microparticles having a maximum particle diameter less than about 200 μm and comprising the prostamide component and the polymeric component; and terminally sterilizing the polymeric microparticles, wherein at least 80% of the prostamide component remains stable after sterilization; and wherein the prostamide component comprises a compound having the formula (I) wherein the dashed bonds represent a single or double bond which can be in the cis or trans configuration, A is an alkylene or alkenylene radical having from two to six carbon atoms, which radical may be interrupted by one or more oxide radicals and substituted with one or more hydroxy, oxo, alkyloxy or alkylcarboxy groups wherein said alkyl radical comprises from one to six carbon atoms; B is a cycloalkyl radical having from three to seven carbon atoms, or an aryl radical, selected from the group consisting of hydrocarbyl aryl and heteroaryl radicals having from four to ten carbon atoms wherein the heteroatom is selected from the group consisting of nitrogen, oxygen and sulfur atoms; X is —N(R 4 ) 2 wherein R 4 is selected from the group consisting of hydrogen, a lower alkyl radical having from one to six carbon atoms, wherein R 5 is a lower alkyl radical having from one to six carbon atoms; Z is ═O or represents 2 hydrogen radicals; one of R 1 and R 2 is ═O, —OH or a —O(CO)R 6 group, and the other one is —OH or —O(CO)R 6 , or R 1 is ═O and R 2 is H, wherein R 6 is a saturated or unsaturated acyclic hydrocarbon group having from 1 to about 20 carbon atoms, or —(CH 2 ) m R 7 wherein m is 0 or an integer of from 1 to 10, and R 7 is cycloalkyl radical, having from three to seven carbon atoms, or a hydrocarbyl aryl or heteroaryl radical, as defined above, or a pharmaceutically-acceptable salt thereof.