Dry Granulation Binders, Products, and Use Thereof

Abstract

A method for the preparation of microcrystalline cellulose containing tablets by roller compaction followed by tabletting is disclosed. A tablet formulation is converted to a dry granulate by roller compaction, and the dry granulate lubricated dry granulate and compacted to a tablet. The tablet formulation comprises at least one active, an microcrystalline cellulose containing material, and, optionally other pharmaceutically acceptable excipients. The microcrystalline cellulose containing material has a maximum primary compaction tensile strength of at least 9 MPa or at least 9.5 MPa and a secondary compaction tensile strength of at least 5 MPa, at least 5.5 MPa, or at least 6 MPa. A method for evaluating binders is also disclosed.

1 . A composition, wherein:
 the composition comprises at least 60 wt % of a microcrystalline cellulose containing material;   the composition has a primary tensile strength of at least 9.5 MPa after a primary compaction at 250 MPa; and   the composition has a secondary tensile strength of at least 5.5 MPa after a primary compaction at 250 MPa and a secondary compaction at 250 MPa.   
     
     
         2 . The composition of  claim 1  in which:
 the microcrystalline cellulose containing material is microcrystalline cellulose co-processed with at least one sugar alcohol, 
 the ratio of microcrystalline cellulose to the at least one sugar alcohol is about 70:30 to about 95:5, and 
 the at least one sugar alcohol has at least four carbon atoms. 
 
     
     
         3 . The composition of  claim 2  in which the at least one sugar alcohol is mannitol. 
     
     
         4 . The composition of  claim 3  in which the composition comprises at least 65 wt % of the microcrystalline cellulose containing material. 
     
     
         5 . A granulate formulation comprising the composition of  claim 1 , at least one active, and at least one lubricant. 
     
     
         6 . The granulate formulation of  claim 5  in which the microcrystalline cellulose containing material is microcrystalline cellulose co-processed with mannitol. 
     
     
         7 .- 9 . (canceled) 
     
     
         10 . A method comprising the steps of:
 applying pressure to a granulate formulation to form a compact, and   milling the compact to form a granulate;   wherein:   the granulate formulation comprises a binder composition, at least one active, at least one excipient, and at least one lubricant,   the binder composition comprises at least 60 wt % of a microcrystalline cellulose containing material, and either   (1) the binder composition has a maximum primary tensile strength of at least 9.5 MPa after a primary compaction at 250 MPa and a secondary tensile strength of at least 5.5 MPa after a primary compaction at 250 MPa and a secondary compaction at 250 MPa, or   (2) the microcrystalline cellulose containing material is microcrystalline cellulose co-processed with a material selected from the group consisting of sugar alcohols and carboxymethyl cellulose, the binder composition has a maximum primary tensile strength of at least 9.0 MPa after a primary compaction at 250 MPa and a secondary tensile strength of at least 5.0 MPa after a primary compaction at 250 MPa and a secondary compaction after a primary compaction at 250 MPa.   
     
     
         11 . The method of  claim 10  in which:
 the microcrystalline cellulose containing material is microcrystalline cellulose co-processed with at least one sugar alcohol, 
 the ratio of microcrystalline cellulose to the at least one sugar alcohol is about 70:30 to about 95:5, and 
 the at least one sugar alcohol has at least four carbon atoms. 
 
     
     
         12 . The method of  claim 11  in which the at least one sugar alcohol is mannitol. 
     
     
         13 . The method of  claim 10  in which the microcrystalline cellulose containing material is microcrystalline cellulose co-processed with carboxymethyl cellulose. 
     
     
         14 . The method of  claim 10  in which the step of applying pressure is carried out by roller compaction. 
     
     
         15 . The method of  claim 10  additionally comprising the step of compacting the granules to form a solid dosage form. 
     
     
         16 . A solid dosage form prepared by the method of  claim 15 . 
     
     
         17 . The solid dosage form of  claim 16  in which in which the microcrystalline cellulose containing material is microcrystalline cellulose co-processed with mannitol, and the ratio of microcrystalline cellulose to mannitol is about 70:30 to about 95:5. 
     
     
         18 . The solid dosage form of  claim 17  in which the solid dosage form has a tensile strength of at least 2 MPa. 
     
     
         19 . The solid dosage form of  claim 16  in which in which the microcrystalline cellulose containing material is microcrystalline cellulose co-processed with carboxymethyl cellulose. 
     
     
         20 . The solid dosage form of  claim 19  in which the solid dosage form has a tensile strength of at least 2 MPa. 
     
     
         21 . A method of evaluating binders, in which the binder comprises at least about 40 wt % of a microcrystalline cellulose containing material; the method comprising the steps of:
 1) compacting the binder at 250 Pa and measuring the primary tensile strength;   2) compacting the binder formed in step 1) at 250 Pa and measuring the secondary tensile strength; and   3) selecting binders that in which either (1) the binder has a primary tensile strength of at least 9.5 MPa and a secondary tensile strength of at least 6 MPa; or (2) the microcrystalline cellulose containing material is microcrystalline cellulose co-processed with a material selected from the group consisting of sugar alcohols and carboxymethyl cellulose, and the binder has a maximum primary tensile strength of at least 9.0 MPa and a secondary tensile strength of at least 5.0 MPa.   
     
     
         22 . The method of  claim 21  in which the binder comprises at least about 60 wt % microcrystalline cellulose