Patent EA-004777-B1 (EA)
Title: Continuos production of pharmaceutical granulation
Inventor: GHEBRE-SELLASSIE ISAAC
IPC: B29C48/285
Filed: 2001-05-14
Abstract: 1. A method for making a compressible pharmaceutical granulation by mixing at least one pharmaceutically active ingredient with excipients, binders, and liquids to form a wet mixture, chopping said wet mixture into a wet granulation, and drying said wet granulation, the improvement comprising: forming said wet granulation in a twin screw wet granulator chopper by feeding at least one pharmaceutically active ingredient, excipients, binders, and liquids to said granulator-chopper at preselected locations along the length thereof, removing said granulation continuously, without extrusion, at one end of said granulator-chopper, and drying said granulation. 2. The method of Claim 1 wherein said wet mixture is granulated by the rotation of twin screws of said granulator-chopper, said screws having interengaging threads adapted to rotate in the same or opposite directions and granulate said mixture. 3. The method of Claim 2 wherein said wet mixture is granulated by thread-free zones of said screws and said granulated mixture is chopped to form discrete granulation particles. 4. A twin screw wet granulator-chopper for granulating an active ingredient and additives comprising: a housing containing feed points for solids and liquids containing at least one active ingredient and additives; twin screws within the housing, the screws having interengaging threads adapted to rotate in the same or opposite directions; a motor for rotating the twin screws to mix the solids and liquids into a granulation; an open end for discharging the granulation; and means for chopping the granulation into discrete particles. 5. The twin screw wet granulator-chopper of Claim 4 further comprising one or both of reverse threads and thread-free zones for granulating the solids and liquids. 6. The twin screw wet granulator-chopper of Claim 4 further comprising at least one member from the group consisting of kneading discs, combing mixers, gear mixers, pin mixers, and calender gap mixers, for granulating the solids and liquids. 7. The twin screw wet granulator-chopper of Claim 4 wherein the chopping means is flush with the open end or extends beyond the open end of the twin screw wet granulator-chopper. 8. A continuous processing system for producing a high dose pharmaceutical granulation comprising: a twin screw wet granulator-chopper; a powder feeder adapted to feed a powder to said twin screw wet granulator-chopper, said powder comprising a pharmaceutically active ingredient; a first liquid feeder adapted to feed a liquid to said twin screw wet granulator-chopper; wherein said powder feeder and said liquid feeder are coupled to said twin screw wet granulator-chopper and adapted to feed said powder and said liquid at an inlet of said twin screw wet granulator-chopper; and, wherein said powder and said liquid flow through said twin screw wet granulator-chopper from said inlet to an outlet of said twin screw wet granulator-chopper; said twin screw wet granulator-chopper comprising: a) a first conveying element having at least one conveying element pitch; b) a second conveying element having at least one conveying element pitch and positioned to contact said pharmaceutically active ingredient after said first conveying element, wherein said second conveying element has at least one pitch less than at least one pitch of said first conveying element; c) a first mixing element positioned in between said first and said second conveying elements; d) at least one chopping element positioned to contact said pharmaceutically active ingredient after said second conveying element; and a housing surrounding said elements, said housing defining said inlet, and a non-extruding opening at said outlet. 9. The continuous processing system of Claim 8 further comprising: a third conveying element having at least one conveying element pitch, said third conveying element positioned to contact said pharmaceutically active ingredient after said second conveying element and before said chopping element, wherein at least one pitch of said third conveying element is less than at least one pitch of said second conveying element; and a second mixing element positioned in between said second and said third conveying elements. 10. The continuous processing system of Claim 8, further comprising a second liquid feeder. 11. The continuous processing system of Claim 8, wherein said powder feeder and said first liquid feeder are both coupled to said twin screw wet granulator-chopper at a position where said first conveying element is positioned in said housing. 12. The continuous processing system of Claim 8, wherein said second liquid feeder is coupled to said twin screw wet granulator-chopper at a position between where said first conveying element and said first mixing element are positioned in said housing. 13. The continuous processing system of Claim 8, wherein said active pharmaceutical ingredient comprises nelfinavir mesylate. 14. The continuous processing system of Claim 8, wherein said liquid comprises water. 15. A method for producing a high dose pharmaceutical granulation comprising: (a) feeding a powder comprising a pharmaceutically active ingredient to a twin screw wet granulator-chopper, said powder having a density less than 0.2 g/ml; (b) feeding a liquid to said twin screw wet granulator-chopper; (c) contacting said liquid and said powder with a first conveying element of said twin screw wet granulator-chopper, said first conveying element having at least one pitch; (d) contacting said liquid and said powder with a first mixing element of said twin screw wet granulator-chopper to form a wet mass; (e) contacting said wet mass with a second conveying element of said twin screw wet granulator-chopper, said second conveying element having at least one pitch, wherein at least one pitch of said second conveying element is less than at least one pitch of said first conveying element; and (f) contacting said wet mass with a chopping element of said twin screw wet granulator-chopper and chopping said wet mass into a granulation.