Research On Key Technologies Of Twin-screw Wet Controlled Granulation Based On Process And Equipment Collaboration

Although foreign research has achieved relatively abundant results,the regulation mechanism of solid oral preparation granulation particle size,apparent quality and yield has not been fully clarified.There is a serious lack of industrial application and related theoretical and experimental research of continuous high shear twin-screw wet granulation process and equipment in China,which is urgent to develop the key technology and equipment of continuous high shear twin-screw wet granulation.In view of the industry common problem that it is difficult to control the key quality attributes(uniformity of particle size distribution,apparent quality of particle and granulation yield)of the granulation process in China,based on the Edinburgh Elastic-Plastic Adhesion contact model,the simulation method of the continuous high-shear counter-rotating twin-screw wet granulation process was constructed,the cooperative coupling evolution mechanism of process parameters-particle size distribution uniformity and yield was simulated and observed.On this account,the regulation mechanism of key quality attributes for twin-screw wet granulation was explained.The main conclusions are as follows:Based on the Edinburgh Elastic-Plastic Adhesion contact model,the three-dimensional simulation method of continuous high shear counter meshing twin-screw wet granulation process is constructed,which lays a foundation for the research on the key technology of high shear twin-screw wet controllable granulation based on the cooperation of process and equipment.The continuous counter meshing twin-screw granulator can prepare spheroidized particles with smooth surface,particle size is positively correlated with feed speed of powder,and negatively correlated with screw speed,the evolution law between granulation yield and powder feeding speed,screw speed shows that the yield increases first and then decreases with the increase of powder feeding speed and screw speed.When the powder feeding speed is 360kg/h or screw speed is 1400rpm,the granulation yield is in the best state,and the optimal granulation yield values are 87.9%and 83.91%.Particle size is positively correlated with surface energy,and negatively correlated with dry to wet particle ratio,the evolution law between granulation yield and surface energy,dry to wet particle ratio shows that the yield increases first and then decreases with the increase of surface energy and dry to wet particle ratio.When the dry to wet particle ratio is 2.33 or surface energy is 12J/m~2,the granulation yield is in the best state,and the optimal granulation yield values are 87.19%and 81.48%.Based on above research results,the technical method for on-line and real-time regulation was proposed in which the size and yield of qualified particles are controlled by the frequency conversion speed control of the screw for powder weight loss feeding device and reverse meshing high shear twin-screw wet granulator.The regulation mechanism of particle size is proposed as follows:the granulation particle size is controlled by the impact probability and powder agglomeration contact force,and there is a positive correlation with them.The impact probability has a positive correlation with the residual residence time and powder distribution density,and the powder agglomeration contact force has a positive correlation with the powder impact velocity.