Matrix compositions for controlled delivery of drug substances

Abstract

A novel matrix composition for pharmaceutical use. The matrix composition has been designed so that it is especially suitable in those situation where an improved bioavailability is desired and/or in those situation where a slightly or insoluble active substance is employed. Accordingly, a controlled release pharmaceutical composition for oral use is provided in the form of a coated matrix composition, the matrix composition comprising i) a mixture of a first and a second polymer that have plasticizing properties and which have melting points or melting intervals of a temperature of at the most 200° C., the first polymer being selected from the group consisting of polyethylene glycols and polyethylene oxides, and the second polymer being selected form block copolymer of ethylene oxide and propylene oxide including poly(ethylene-glycol-b-(DL-lactic acid-co-glycolic acid)-b-ethylene glycol (PEG-PLGA PEG), poly((DL-lactic acid-co-glycolic acid)-g-ethylene glycol) (PLGA-g-PEG), poloxamers and polyethylene oxide-polypropylene oxide (PEO-PPO), ii) a therapeutically, prophylactically and/or diagnostically active substance, the matrix composition being provided with a coating having at least one opening exposing at one surface of said matrix, wherein the active substance is released with a substantially zero order release.

1 .- 69 . (canceled) 
     
     
         70 . A controlled release pharmaceutical composition for oral use in the form of a coated matrix composition, the matrix composition comprising
 (i) a mixture of a first and a second polymer that have plasticizing properties and which have melting points or melting intervals of a temperature of at the most 200° C.,
 the first polymer being selected from the group consisting of polyethylene glycols and polyethylene oxides having a molecular weight of at least about 20,000 daltons in crystalline and/or amorphous form or a mixture of such polymers, and 
 the second polymer being selected from block copolymer of ethylene oxide and propylene oxide, and 
   (ii) a therapeutically, prophylactically and/or diagnostically active substance, wherein the concentration of the second polymer in the matrix composition is from about 5 to about 90% w/w,   the matrix composition being provided with a coating, which is substantially insoluble in and impermeable to body fluids during the intended release periods, the coating having at least one opening exposing one surface of said matrix,   the coating comprising one or more coating polymers which can be processed by extrusion, solution, or in the form of a dispersion, the one or more coating polymers being selected from the group consisting of cellulose acetate, polyamide, polyethylene, polyethylene terephthalate, polypropylenem polyurethane, polyvinyl acetate, polyvinyl chloride, silicone rubber, latex, polyhydroxybutyrate, polyhydroxyvalerate, teflon, polylactic acid or polyglycolic acid and copolymers thereof, copolymers such as ethylene vinyl acetate (EVA), styrene-butadienestyrene (SBS) and styrene-isoprene-styrene (SIS).   
     
     
         71 . The composition according to  claim 70 , wherein the polyethylene glycol and/or polyethylene oxide has a molecular weight selected from the group consisting of from about 20,000 to about 700,000 daltons, from about 20,000 to about 600,000 daltons, from about 35,000 to about 500,000 daltons, from about 35,000 to about 400,000 daltons, from about 35,000 to about 300,000 daltons, from about 50,000 to about 300,000 daltons, about 35,000 daltons, about 50,000 daltons, about 75,000 daltons, about 100,000 daltons, about 150,000 daltons, about 200,000 daltons, about 250,000 daltons, about 300,000 daltons and about 400,000 daltons. 
     
     
         72 . The composition according to  claim 70 , wherein the concentration of the first polymer in the matrix composition is selected from the group consisting of from about 10 to about 99.5% w/w, from about 20 to about 99% w/w, from about 30 to about 99% w/w, from about 35 to about 95% w/w, from about 35 to about 90% w/w, from about 35 to about 85% w/w, from about 35 to about 80% w/w, from about 40 to about 75% w/w, from about 45 to about 70% w/w, from about 45 to about 65% w/w, from about 55 to about 85% w/w and from about 60 to about 85% w/w. 
     
     
         73 . The composition according to  claim 70 , wherein the second polymer has a molecular weight of at least about 2,000 daltons. 
     
     
         74 . The composition according to  claim 70 , wherein the second polymer is a poloxamer having a molecular weight selected from the group consisting of from about 2,000 daltons to about 20,000 daltons, from about 4,000 daltons to about 15,000 daltons and from about 6,000 daltons to about 10,000 daltons. 
     
     
         75 . The composition according to  claim 70 , wherein the second polymer has a melting point selected from the group consisting of from about 20-120° C., from about 30-100° C. and from about 40-80° C. 
     
     
         76 . The composition according to  claim 70 , wherein the second polymer has a HLB value selected from the group consisting of at least about 18 and at least about 20. 
     
     
         77 . The composition according to  claim 70 , wherein the concentration of the second polymer in the matrix composition is selected from the group consisting of from about 10% to about 90% w/w, from about 10% to about 80% w/w, from about 10% to about 70% w/w, from about 10% to about 60%, from about 10% to about 50%, from about 15% to about 50% w/w, from about 10% to about 45% w/w, from about 10% to about 40% w/w, from about 15% to about 40% w/w, from about 15% to about 35% w/w and from about 15% to about 30% w/w. 
     
     
         78 . The pharmaceutical composition according to  claim 70 , wherein said composition provides controlled release of the active substance into an aqueous medium by erosion of at least one surface of the composition. 
     
     
         79 . The composition according to  claim 70 , wherein the active substance is present in any of its crystalline, polymorphous or amorphous forms or mixtures thereof. 
     
     
         80 . A pharmaceutical composition according to  claim 70 , wherein the active substance at least partially is present in a molecular dispersion. 
     
     
         81 . The composition according to  claim 70 , further comprising a stabilizing agent. 
     
     
         82 . The composition according to  claim 81 , wherein the stabilizing agent is selected from the group consisting of inorganic acids, inorganic bases, inorganic salts, organic acids or bases and pharmaceutically acceptable salts thereof, saccharides, oligosaccharides, polysaccharides, cellulose cellulose derivatives, and mixtures thereof. 
     
     
         83 . The composition according to  claim 70 , wherein the block copolymer of ethylene oxide and propylene oxide is selected from the group consisting of poly(ethylene-glycol-b-(DL-lactic acid-co-glycolic acid)-b-ethylene glycol (PEG-PLGA PEG), poly((DL-lactic acid-co-glycolic acid)-g-ethylene glycol) (PLGA-g-PEG), poloxamers and polyethylene oxide-polypropylene oxide (PEO-PPO). 
     
     
         84 . A method for preparing a composition according to  claim 70 , wherein the method comprises
 injection moulding of a melted or semi-solid mixture of the individual components making up the composition into a suitable form,   application of a coating by means of injection moulding and   cooling the thus prepared coated composition to solidify the composition.