Controlled release dosage forms

Abstract

The invention provides stable controlled release monolithic coating compositions for use in coating pharmaceutical oral dosage forms comprising a polyglycol having a melting point greater than 55° C. and an aqueous dispersion of a neutral ester copolymer lacking functional groups.

1 - 40 . (canceled) 
     
     
         41 . A controlled release oral dosage form comprising:
 a) a core, wherein said core comprises:
 i) an effective amount of at least one therapeutically active agent, and 
 ii) at least one first pharmaceutically acceptable excipient, and 
   b) a stable controlled release monolithic coating surrounding the core, wherein the stable controlled release monolithic coating is formed by a process comprising
 coating the core with a coating composition to form a coated core, and 
 curing the coated core to form the stable controlled release monolithic coating, 
 wherein the coating composition comprises 
 i) an aqueous dispersion of a neutral ester copolymer without any functional groups; 
 ii) a poly glycol having a melting point of at least 55° C., and 
 iii) at least one second pharmaceutically acceptable excipient; 
   wherein the curing is conducted at a temperature at least equal to or greater than the melting point of the poly glycol, and   wherein the stable controlled release monolithic coating hydrates when placed into water.   
     
     
         42 . The controlled release oral dosage form of  claim 41 , wherein the aqueous dispersion of neutral ester copolymer without any functional groups is selected from the group consisting of a 30% aqueous dispersion of a neutral copolymer based on ethyl acrylate and methyl methacrylate, a 40% aqueous dispersion of a neutral copolymer based on ethyl acrylate and methyl methacrylate, and combinations thereof. 
     
     
         43 . The controlled release oral dosage form of  claim 42 , wherein the aqueous dispersion of neutral ester copolymer without any functional groups comprises a 30% aqueous dispersion of a neutral copolymer based on ethyl acrylate and methyl methacrylate. 
     
     
         44 . The controlled release oral dosage form of  claim 42 , wherein the aqueous dispersion of neutral ester copolymer without any functional groups comprises a 40% aqueous dispersion of a neutral copolymer based on ethyl acrylate and methyl methacrylate. 
     
     
         45 . The controlled release oral dosage form of  claim 41 , wherein the neutral ester copolymer without any functional groups is present in an amount of from about 1% to about 35% by weight of the coating composition. 
     
     
         46 . The controlled release oral dosage form of  claim 45 , wherein the neutral ester copolymer without any functional groups is present in an amount of from about 1% to about 25% by weight of the coating composition. 
     
     
         47 . The controlled release oral dosage form of  claim 46 , wherein the neutral ester copolymer without any functional groups is present in an amount of from about 1% to about 7% of the coating composition. 
     
     
         48 . The controlled release oral dosage form of  claim 41 , wherein the poly glycol is selected from the group consisting of polyethylene glycol 6000, polyethylene glycol 8000, polyethylene glycol 10000, polyethylene glycol 20000, Poloxamer 188, Poloxamer 338, Poloxamer 407, polyethylene oxides, polyoxyethylene alkyl ethers, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, and combinations thereof. 
     
     
         49 . The controlled release oral dosage form of  claim 41 , wherein the poly glycol is selected from the group consisting of polyethylene glycol 6000, polyethylene glycol 8000, polyethylene glycol 10000, polyethylene glycol 20000 and any combination thereof. 
     
     
         50 . The controlled release oral dosage form of  claim 49 , wherein the polyethylene glycol comprises polyethylene glycol 8000. 
     
     
         51 . The controlled release oral dosage form of  claim 41 , wherein the poly glycol is present in an amount of from about 0.1% to about 10% by weight of the coating composition. 
     
     
         52 . The controlled release oral dosage form of  claim 41 , wherein the poly glycol is present in an amount of from about 0.1% to about 5% by weight of the coating composition. 
     
     
         53 . The controlled release oral dosage form of  claim 52 , wherein the poly glycol is present in an amount of from about 0.1% to about 3% by weight of the coating composition. 
     
     
         54 . The controlled release oral dosage form of  claim 53 , wherein said poly glycol is present in an amount of from about 0.1% to about 0.5% by weight of the coating composition. 
     
     
         55 . The controlled release oral dosage form of  claim 41 , wherein the at least one second pharmaceutically acceptable excipient is selected from the group consisting of an anti-tacking agent, an emulsifying agent, a hydrophilic agent, an antifoaming agent, a flavorant, a colorant, a sweetener and any combination thereof. 
     
     
         56 . The controlled release oral dosage form of  claim 55 , comprising the anti-tacking agent, wherein the anti-tacking agent is selected from the group consisting of adipic acid, magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, glyceryl monostearate, talc, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate and any combination thereof. 
     
     
         57 . The controlled release oral dosage form of  claim 56 , wherein the anti-tacking agent is talc. 
     
     
         58 . The controlled release oral dosage form of  claim 56 , wherein the anti-tacking agent is present in an amount of from about 1% to about 15% by weight of the coating composition. 
     
     
         59 . The controlled release oral dosage form of  claim 58 , wherein the anti-tacking agent is present in an amount of from about 1% to about 7% by weight of the coating composition. 
     
     
         60 . The controlled release oral dosage form of  claim 55 , comprising the hydrophilic agent, wherein said hydrophilic agent is selected from the group consisting of hydroxypropyl cellulose, hydroxypropyl methylcellulose and any combination thereof. 
     
     
         61 . The controlled release oral dosage form of  claim 60 , wherein the hydrophilic agent comprises hydroxypropyl methylcellulose. 
     
     
         62 . The controlled release oral dosage form of  claim 60 , wherein the hydrophilic agent is present in an amount from about 0.1% to about 10% by weight of the coating composition. 
     
     
         63 . The controlled release oral dosage form of  claim 62 , wherein said hydrophilic agent is present in an amount from about 0.1% to about 6% by weight of the coating composition. 
     
     
         64 . The controlled release oral dosage form of  claim 63 , wherein the hydrophilic agent is present in an amount from about 0.1% to about 3% by weight of the coating composition. 
     
     
         65 . The controlled release oral dosage form of  claim 55 , comprising the anti-foaming agent, wherein said anti-foaming agent is selected from the group consisting of silicon oil, simethicone and any combination thereof. 
     
     
         66 . The controlled release oral dosage form of  claim 65 , wherein the anti-foaming agent comprises simethicone. 
     
     
         67 . The controlled release oral dosage form of  claim 65 , wherein the anti-foaming agent is present in an amount up to about 0.5% by weight of the coating composition. 
     
     
         68 . The controlled release oral dosage form of  claim 67 , wherein the anti-foaming agent is present in an amount from about 0.1% to about 0.4% by weight of the coating composition. 
     
     
         69 . The controlled release oral dosage form of  claim 55 , comprising the emulsifying agent, wherein said emulsifying agent is selected from the group consisting of a polysaccharide, a glycerol ester, a cellulose ether, a sorbitan ester, a polysorbate and any combination thereof. 
     
     
         70 . The controlled release oral dosage form of  claim 69 , wherein the emulsifying agent comprises the polysorbate, and wherein said polysorbate is polyoxyethylene sorbitan mono-oleate. 
     
     
         71 . The controlled release oral dosage form of  claim 70 , wherein the polyoxyethylene sorbitan mono-oleate is present in an amount of up to about 0.5% by weight of the coating composition. 
     
     
         72 . The controlled release oral dosage form of  claim 71 , wherein the polyoxyethylene sorbitan mono-oleate is present in an amount of from about 0.1% to about 0.3% by weight of the coating composition. 
     
     
         73 . The controlled release oral dosage form of  claim 55 , comprising the colorant, wherein said colorant is selected from the group consisting of iron oxide pigments, titanium dioxide, aluminum lakes and any combination thereof. 
     
     
         74 . The controlled release oral dosage form of  claim 73 , wherein the colorant comprises titanium dioxide. 
     
     
         75 . The controlled release oral dosage form of  claim 73 , wherein the colorant is present in an amount of from about 0.1% to about 10% by weight of the coating composition. 
     
     
         76 . The controlled release oral dosage form of  claim 73 , wherein the colorant is present in an amount of from about 0.1% to about 5% by weight of the coating composition. 
     
     
         77 . The controlled release oral dosage form of  claim 76 , wherein the colorant is present in an amount of from about 0.1% to about 2% by weight of the coating composition. 
     
     
         78 . The controlled release oral dosage form of  claim 41 , wherein the controlled release oral dosage form is selected from the group consisting of a tablet and a capsule. 
     
     
         79 . The controlled release oral dosage form of  claim 41 , wherein the at least one therapeutically active agent comprises metformin, a pharmaceutically acceptable salt thereof, or a combination thereof. 
     
     
         80 . The controlled release oral dosage form of  claim 41 , wherein the at least one first pharmaceutically acceptable excipient is selected from the group consisting of a glidant, a lubricant, an anti-adherent, a sorbent, a diluent, a filler, a binder, and combinations thereof. 
     
     
         81 . A controlled release oral dosage form comprising:
 a) a core, wherein said core comprises:
 i) an effective amount of metformin hydrochloride, and 
 ii) one or more first pharmaceutically acceptable excipients, and 
   b) a stable controlled release monolithic coating surrounding the core, wherein the stable controlled release monolithic coating is formed by a process comprising:
 coating the core with a coating composition to form a coated core, and 
 curing the coated core to form the stable controlled release monolithic coating, 
 wherein the coating composition comprises 
 i) an ethyl acrylate and methyl methacrylate copolymer dispersion; 
 ii) a poly glycol comprising at least one of polyethylene glycol 6000, polyethylene glycol 8000, polyethylene glycol 10000, polyethylene glycol 20000, and a mixture thereof; 
 iii) one or more second pharmaceutically acceptable excipients; and 
   wherein the curing is conducted at a temperature at least equal to or greater than the melting point of the poly glycol, and   wherein the stable controlled release coating hydrates when placed into water.   
     
     
         82 . The controlled release oral dosage form of  claim 81 , wherein the effective amount of metformin hydrochloride is from about 5% to about 99% by weight of the core. 
     
     
         83 . A controlled release oral dosage form comprising:
 a) a core, wherein said core comprises:
 i) an effective amount of at least one therapeutically active agent, and 
 ii) at least one first pharmaceutically acceptable excipient, and 
   b) a stable controlled release monolithic coating surrounding the core,
 wherein said coating comprises 
 i) a neutral ester copolymer without any functional groups; 
 ii) a poly glycol having a melting point of at least 55° C., and 
 iii) at least one second pharmaceutically acceptable excipient; 
   wherein the stable controlled release monolithic coating hydrates when placed into water.   
     
     
         84 . The controlled release oral dosage form of  claim 83 , wherein the neutral ester copolymer without any functional groups is selected from the group consisting of a 30% aqueous dispersion of a neutral copolymer based on ethyl acrylate and methyl methacrylate, a 40% aqueous dispersion of a neutral copolymer based on ethyl acrylate and methyl methacrylate, and combinations thereof. 
     
     
         85 . The controlled release oral dosage form of  claim 83 , wherein the poly glycol is selected from the group consisting of polyethylene glycol 6000, polyethylene glycol 8000, polyethylene glycol 10000, polyethylene glycol 20000 and any combination thereof.