Compact member, method of manufacturing and use thereof

Abstract

The invention relates to a compact member comprising a plurality of porous cellulose matrices (PCMs), and providing extended release of an active compound located in the pores of said PCMs together with a release modifying agent. The friability of the compact member is less than 2.1%, and the disintegration time in-vitro of said compact member is less than 240 minutes. The compact member is manufactured by exposing a plurality of PCMs to an active compound and a release modifying agent, in optional sequence or mixture, for a time sufficient for said active compound and release modifying agent to fill the pores in said PCMs to a preselected level. The PCMs are sub-sequently compacted to a desired shape. The invention further relates to use of the compact members for administration of a drug.

1 . A compact member comprising a plurality of porous cellulose matrices (PCMs), and providing extended release of an active compound contained therein, characterized in that 
 a) said active compound and a release-modifying agent is located in the pores of said PCMs;    b) the friability of the compact member is less than 2.1%, suitably less than 1%, preferably less than 0.5%; and    c) the disintegration time in-vitro (measured with the USP method with discs) of said compact member is less than about 240 minutes, suitably less than 90 minutes, preferably less than 60 minutes.    
     
     
         2 . The compact member according to  claim 1 , wherein the radial tensile strength of the compact member is higher than about 0.1 MPa, preferably higher than 0.5 MPa.  
     
     
         3 . The compact member according to  claim 1  or  2 , wherein said release-modifying agent is a lipid.  
     
     
         4 . The compact member according to  claim 3 , wherein said lipid is selected from the group consisting of fatty acids, e.g. stearic acid, long chain alcohols, e.g. cetostearyl alcohol, naturally occurring or synthetic waxes, glyceryl esters of fatty acids, e.g. glyceryl monostearate, glyceryl distearate, or glyceryl tristearate, aliphatic hydrocarbons, e.g. hard paraffin, polyglycerol esters of fatty acids, and any mixture thereof.  
     
     
         6 . The compact member according to any preceding claim, further comprising up to about 10% by weight of talc, preferably up to 5%.  
     
     
         7 . The compact member according to any preceding claim, further comprising up to about 1% by weight of a lubricant, e.g. magnesium stearate.  
     
     
         8 . The compact member according to any preceding claim, comprising up to about 50% by weight of said active compound, preferably up to 2.5%.  
     
     
         9 . The compact member according to any preceding claim, wherein said active compound is a drug.  
     
     
         10 . The compact member according to  claim 9 , wherein said drug is hydrophilic.  
     
     
         11 . The compact member according to  claim 9  or  10 , wherein said drug has a biological half-life of less than about 20 hours.  
     
     
         12 . The compact member according to any preceding claim, being a tablet suitable for oral administration.  
     
     
         13 . The compact member according to any of claims  1 - 8 , wherein said active compound is selected from the group consisting of fertilizers, herbicides and pesticides.  
     
     
         14 . A method of manufacturing a compact member providing extended release of an active compound, the method comprising 
 a) exposing a plurality of PCMs to an active compound and a release modifying agent, in optional sequence or mixture, for a time sufficient for said active compound and release modifying agent to fill the pores in said PCMs to a preselected level; and    b) compacting said PCMs comprising said active compound and release-modifying agent, to a desired shape.    
     
     
         15 . The method according to  claim 14 , wherein the pressure in the compacting step is less than about 500 MPa, preferably in the range of from 10 up to 200 MPa.  
     
     
         16 . The method according to  claim 14  or  15 , wherein said release-modifying agent is a lipid.  
     
     
         17 . The method according to  claim 16 , wherein said lipid is selected from the group consisting of fatty acids, e.g. stearic acid, long chain alcohols, e.g. cetostearyl alcohol, naturally occurring or synthetic waxes, glyceryl esters of fatty acids, e.g. glyceryl mono-stearate, glyceryl distearate, or glyceryl tristearate, aliphatic hydrocarbons, e.g. hard paraffin, polyglycerol esters of fatty acids, and any mixture thereof.  
     
     
         18 . The method according to any of claims  14 - 17 , wherein up to about 10% by weight, preferably up to 5% by weight of talc is incorporated in said compact member.  
     
     
         19 . The method according to any of claims  14 - 18 , wherein up to 1% by weight of a lubricant, e.g. magnesium stearate, is added to the preparation before compaction.  
     
     
         20 . Use of a compact member according to any of claims  1 - 13  for administration of a drug.