湿法制粒工艺办法放大及终点判断.pdf

Page 1 of 40 Wet Granulation: End-Point Determination and Scale-Up By Michael Levin, Ph. D. Metropolitan Computing Corporation East Hanover, New Jersey, USA Keywords: wet granulation, end-point determination, dimensional analysis, scale- up, instrumentation, torque, power consumption. Abstract: Both high-shear and planetary mixers-granulators are routinely instrumented to measure and record various process variables, most commonly, impeller torque and motor power consumption. These variables provide information for end-point determination, reproducibility, and scale-up. Illustrated by several case studies, this article shows how to scale-up scientifically, using a dimensional analysis approach, and offers practical considerations for practitioners in the field of wet granulation. Contents List of Figures.............................................................................................................................. 2 List of Tables............................................................................................................................... 3 INTRODUCTION............................................................................................................................. 4 WHAT IS AN END-POINT?............................................................................................................ 5 WHAT CAN BE MEASURED ON A MIXER-GRANULATOR?...................................................... 5 Current ........................................................................................................................................ 5 Voltage........................................................................................................................................ 5 Capacitance ................................................................................................................................ 5 Conductivity................................................................................................................................. 6 Probe vibration............................................................................................................................ 6 Boots Diosna Probe.................................................................................................................... 6 Chopper Speed........................................................................................................................... 6 Impeller or Motor Shaft Speed.................................................................................................... 6 Motor Slip and Motor Load Analyzer........................................................................................... 6 Impeller Tip Speed...................................................................................................................... 7 Relative Swept Volume............................................................................................................... 7 Temperature................................................................................................................................ 7 Page 2 of 40 Binder Addition Rate................................................................................................................... 7 Power Consumption................................................................................................................... 8 Impeller Torque........................................................................................................................... 9 Torque Rheometer...................................................................................................................... 9 Reaction Torque........................................................................................................................ 10 Other possibilities...................................................................................................................... 10 Emerging Technology: Acoustic................................................................................................ 10 Emerging Technology: Near Infra-Red (NIR) ............................................................................. 11 Emerging Technology: FBRM................................................................................................... 11 END-POINT DETERMINATION.................................................................................................... 11 Torque vs. Power...................................................................................................................... 12 Torque and Power Profiles........................................................................................................ 13 End-Point Optimization ............................................................................................................. 14 End-Point Reproducibility..............................................................。