Drug delivery system

Abstract

The subject invention provides a drug delivery system comprising at least one compartment comprising (i) a drug-loaded thermoplastic polymer core layer, (ii) a drug-loaded thermoplastic polymer intermediate layer and (iii) a non-medicated thermoplastic polymer skin covering the intermediate layer, wherein said core layer is loaded with crystals of a first (pharmaceutically) active compound and said intermediate layer is loaded with crystals of the second (pharmaceutically) active compound.

1 - 59 . (canceled) 
     
     
         60 . A drug delivery system comprising (i) a drug-loaded ethylene-vinyl acetate copolymer core layer, (ii) a drug-loaded ethylene-vinyl acetate copolymer intermediate layer and (iii) a non-medicated ethylene-vinyl acetate copolymer skin covering the intermediate layer, wherein the core layer is loaded with crystals of estradiol, and wherein the intermediate layer is loaded with crystals of nomegestrol acetate (NOMAc). 
     
     
         61 . The drug delivery system of  claim 60 , wherein the core layer forms the core of the drug delivery system. 
     
     
         62 . The drug delivery system of  claim 60 , wherein an additional non-medicated core is covered by the core layer. 
     
     
         63 . The drug delivery system of  claim 60 , wherein an additional non-medicated intermediate layer is between the core layer and the drug-loaded intermediate layer. 
     
     
         64 . The drug delivery system of  claim 60 , wherein the delivery system has the form of a ring, an implant, an intrauterine system (IUS), a helical coil or a spring. 
     
     
         65 . The drug delivery system of  claim 64 , wherein the delivery system has a substantially ring-shaped form and is intended for vaginal administration. 
     
     
         66 . The drug delivery system of  claim 60 , wherein nomegestrol acetate is present at about 5-35% by weight. 
     
     
         67 . The drug delivery system of  claim 60 , wherein nomegestrol acetate is present at about 35% by weight. 
     
     
         68 . The drug delivery system of  claim 60 , wherein the estradiol is present at about 3-27% by weight. 
     
     
         69 . The drug delivery system of  claim 60 , wherein the estradiol is present at about 9-27% by weight. 
     
     
         70 . The drug delivery system of  claim 60 , wherein the estradiol is present at about 3-20% by weight. 
     
     
         71 . The drug delivery system of  claim 60 , wherein the estradiol is present at about 4.5-9% by weight. 
     
     
         72 . The drug delivery system of  claim 60 , wherein the intermediate layer additionally contains an anti-microbial agent. 
     
     
         73 . The drug delivery system of  claim 60 , wherein the core additionally contains an anti-microbial agent. 
     
     
         74 . The drug delivery system of  claim 60 , wherein the intermediate layer is between 75-500 μm. 
     
     
         75 . The drug delivery system of  claim 60 , wherein the remnant content of the nomgestrol acetate after use of the drug delivery system is between and includes 20 to 40% by weight. 
     
     
         76 . The drug delivery system of  claim 60 , wherein the remnant content of the estradiol after use of the drug delivery system is between and includes 20 to 40% by weight. 
     
     
         77 . A method of contraception which comprises the steps of (i) positioning the drug delivery system of  claim 60  within the female vaginal tract (ii) retaining the system within the vaginal tract for at least about 21 days and (iii) removing the system for an approximate one week period to permit menstruation. 
     
     
         78 . A method of manufacturing the three-layered drug delivery system of  claim 60  comprising:
 producing a loaded homogenous polymer core granulate; 
 (ii) producing a loaded homogenous polymer intermediate layer granulate; and 
 (iii) co-extruding the core granulate and the intermediate layer granulate with a polymer skin granulate to form the three-layered drug delivery system. 
 
     
     
         79 . The method according to  claim 78  wherein step (i) comprises:
 a) grounding the core polymer; 
 b) dry powder mixing the grounded polymer with the active compound to be loaded in the core; 
 c) blend extruding the resulting powder mixture of step (b); 
 d) cutting the resulting loaded polymer strands into granules, thereby obtaining a core granulate; 
 e) lubricating the core granulate with a lubricant. 
 
     
     
         80 . The method according to  claim 78  wherein step (ii) comprises:
 a) grounding the intermediate layer polymer; 
 b) dry powder mixing the grounded polymer with the active compound to be loaded in the intermediate layer; 
 c) blend extruding the resulting powder mixture of steps (b); 
 d) cutting the resulting loaded polymer strands into granules, thereby obtaining an intermediate layer granulate; 
 e) lubricating the intermediate granulate with a lubricant.