Trazodone Composition for Once a Day Administration

Abstract

The invention relates to a once a day formulation of trazodone or a trazodone derivative. The formulation contains trazodone or a trazodone derivative and a controlled release excipient so that, once administered orally, the trazodone or the trazodone derivative is maintained at a therapeutic plasma concentration from at least 1 hour to at least 24 hours after initial administration. After administration, the initial therapeutic action takes effect within the first hour and lasts at least about 24 hours. This therapeutic effect remains relatively and substantially stable for the remaining period of 24 hours. The formulations can be used for treating depression and/or sleeping disorders.

1 . A sustained release pharmaceutical composition for once a day oral administration, the composition comprising: about 15% to about 60% by weight trazodone or a derivative thereof, and about 20% to about 50% by weight of cross-linked high amylose starch, wherein the composition, when administered to a mammal, releases the trazodone or derivative thereof so as to maintain a substantially constant effective plasma concentration between about 50 ng/mL and about 3000 ng/mL from at least about one hour to at least about 24 hours after initial administration. 
     
     
         2 .- 3 . (canceled) 
     
     
         4 . The sustained release pharmaceutical composition according to  claim 1 , wherein the composition comprises trazodone hydrochloride. 
     
     
         5 . (canceled) 
     
     
         6 . The sustained release pharmaceutical composition according to  claim 1 , wherein the composition comprises 150 mg of trazodone hydrochloride. 
     
     
         7 . The sustained release pharmaceutical composition according to  claim 6 , wherein the plasma trazodone concentration achieved one hour after ingestion is between about 150 ng/mL and about 500 ng/mL. 
     
     
         8 . The sustained release pharmaceutical composition according to  claim 1 , wherein the composition comprises 300 mg of trazodone hydrochloride. 
     
     
         9 . The sustained release pharmaceutical composition according to  claim 8 , wherein the plasma trazodone concentration one hour after ingestion is between about 300 ng/mL and about 1000 ng/mL. 
     
     
         10 . The sustained release pharmaceutical composition according to  claim 1 , wherein the composition comprises from about 20% to about 50% by weight trazodone or trazodone derivative and from about 20% to about 50% by weight percent of cross-linked high amylose starch. 
     
     
         11 . The sustained release pharmaceutical composition according to  claim 10 , wherein the composition comprises from about 35% to 50% by weight percent trazodone or trazodone derivative and from about 15% to 50% by weight of cross-linked high amylose starch. 
     
     
         12 . (canceled) 
     
     
         13 . The sustained release pharmaceutical composition according to  claim 12 , wherein the cross-linked high amylose starch comprises between about 65% and 75% by weight amylose and is cross-linked with phosphorus oxychloride. 
     
     
         14 . The sustained release pharmaceutical composition according to  claim 13 , wherein the cross-linked high amylose starch comprises hydroxypropyl side chains. 
     
     
         15 . The sustained release pharmaceutical composition according to  claim 14 , wherein the cross-linked high amylose starch is gelatinized. 
     
     
         16 . The sustained release pharmaceutical composition according to  claim 1 , wherein the composition further comprises a pharmaceutical additive. 
     
     
         17 . The sustained release pharmaceutical composition according to  claim 16 , wherein the pharmaceutical additive is selected from a binding agent, a solubilizing agent, an acidifying agent, a pore forming agent, a lubricant, and a glidant. 
     
     
         18 . The sustained release pharmaceutical composition according to  claim 17 , wherein the binding agent comprises hydroxypropylmethylcellulose. 
     
     
         19 . The sustained release pharmaceutical composition according to  claim 17 , wherein the solubilizing agent is selected from povidone or cetylpyridinium chloride. 
     
     
         20 . The sustained release pharmaceutical composition according to  claim 17 , wherein the acidifying agent comprises alginic acid. 
     
     
         21 . The sustained release pharmaceutical composition according to  claim 17 , wherein the pore forming agent comprises sucrose. 
     
     
         22 . The sustained release pharmaceutical composition according to  claim 17 , wherein the lubricant comprises sodium stearyl fumarate. 
     
     
         23 . The sustained release pharmaceutical composition according to  claim 17 , wherein the glidant comprises colloidal silicon dioxide. 
     
     
         24 . The sustained release pharmaceutical composition according to  claim 1 , wherein the mammal is a human. 
     
     
         25 . (canceled) 
     
     
         26 . The sustained release pharmaceutical composition according to  claim 1 , wherein the composition is in the form of a tablet. 
     
     
         27 . The sustained release pharmaceutical composition according to  claim 26 , wherein the tablet is shaped in the form of a caplet. 
     
     
         28 . The sustained release pharmaceutical composition according to  claim 27 , wherein the caplet comprises about 300 mg trazodone. 
     
     
         29 .- 36 . (canceled) 
     
     
         37 . A method of treating depression comprising administering once a day to a person with depression a sustained release pharmaceutical composition according to  claim 1 . 
     
     
         38 .- 42 . (canceled)