Sustained drug release composition

Abstract

The invention relates to a sustained release formulation for delivering one or more pharmaceutically active agents. The formulation comprises cross-linked high amylose starch and at least one pharmaceutically active agent, and optionally can be subdivided into smaller dosage forms where the smaller dosage forms have substantially the same sustained release properties as the formulation from which they were derived. The formulations can provide sustained release for up to at least 24 hours, and because of their divisability permits a recipient of the active agent or the person administering the active agent to titrate the dosage of the agent.

1 . A solid, monolithic sustained release pharmaceutical composition, the composition comprising:
 a. a sustained release matrix having a solvent accessible surface, wherein the matrix comprises cross-linked high amylose starch; and   b. an effective amount of at least one pharmaceutically active agent disposed within the matrix,   wherein the composition has a hardness of greater than 100 N.   
     
     
         2 . The composition of  claim 1 , wherein the hardness is in the range of about 100 N to about 350 N. 
     
     
         3 . The composition of  claim 1 , wherein the composition, when administered to a mammal, achieves an effective plasma concentration of the active agent from at least about 1 hour to at least about 24 hours after initial administration. 
     
     
         4 . The composition of  claim 1 , wherein the solvent accessible surface defines a score that permits the composition to be fractured along the score to produce at least two subunits each having a new solvent accessible surface. 
     
     
         5 . The composition of  claim 4 , wherein at least one of the subunits has substantially the same release kinetics of the active agent as the intact composition from which it is derived. 
     
     
         6 . The composition of  claim 4 , wherein the dissolution profiles of at least one of the subunits and the composition from which it was derived have a similarity factor of at least 50%. 
     
     
         7 . The composition of  claim 6 , wherein the similarity factor is at least 55%. 
     
     
         8 . A solid sustained release pharmaceutical composition comprising:
 a. a sustained release matrix having a solvent accessible surface, wherein the matrix comprises cross-linked high amylose starch; and   b. an effective amount of a pharmaceutically active agent disposed within the matrix,   wherein the composition displays substantially the same release kinetics when the composition is broken to create a new solvent accessible surface.   
     
     
         9 . (canceled) 
     
     
         10 . The composition of  claim 8 , wherein the composition has a hardness of greater than about 100N. 
     
     
         11 . The composition of  claim 10 , wherein the composition has a hardness in the range of from about 100 N to about 180 N. 
     
     
         12 . The composition of  claim 1 , wherein the composition is monolithic. 
     
     
         13 - 22 . (canceled) 
     
     
         23 . The composition of  claim 1  comprising from about 15% to about 60% by weight of the active ingredient and from about 15% to about 85% by weight of the starch. 
     
     
         24 . The composition of  claim 23  comprising from about 20% to about 50% by weight of the active ingredient and from about 20% to about 50% by weight of the starch. 
     
     
         25 . The composition of  claim 24  comprising from about 35% to about 50% by weight of the active ingredient and from about 20% to about 50% by weight of the starch. 
     
     
         26 . The composition of  claim 1 , wherein the starch is crosslinked with phosphorus oxychloride. 
     
     
         27 . The composition of  claim 1 , wherein the starch comprises hydroxypropyl side chains. 
     
     
         28 - 35 . (canceled) 
     
     
         36 . The composition of  claim 1 , wherein the composition is in the form of a tablet. 
     
     
         37 . The composition of  claim 36 , wherein the tablet has a score. 
     
     
         38 - 41 . (canceled) 
     
     
         42 . A method of treating a mammal, the method comprising administering too the mammal the composition of  claim 1 .