| The international solid oral preparation manufacring industry has entered the era of continuous and controllable manufacturing,but up to now,there is still a lack of research on the collaborative integration digital virtual prototype simulation design platform between twin-screw high shear wet granulation process and equipment,and D11 small twin-screw high shear wet granulation machine,relevant research reports are rare.Focusing on the above technical difficulties,the research on the collaborative integration digital virtual prototype simulation design platform between twin screw high shear wet granulation process and equipment,and the key technologies of D11 small twin screw high shear wet granulation machine have been carried out.By means of which,the synergistic coupling evolution law of the key quality attributesstructural characteristics-screw scale-characteristics of granulating binder was constructed,the virtual functional prototype of D11 small twin screw high shear wet granulator was developed,its granulation performance and key quality attribute technical indicators are evaluated.In order to seek quality through science and ensure success through technology,the comprehensive and refined regulation technologies was constructed for the entire process,which provides technical support for continuous controllable manufacturing of twin screw high shear wet granulation.Based on the coupling of the liquid bridge normal force model and the viscoelastic plastic contact EEPA or JKR contact model,a theoretical model describing the granulation process of a twin screw high shear wet granulation machine was constructed,which can reflect the liquid bridge effect formed by the granulation liquid spray and the viscous contact characteristics of fine powder particles of wetting and softening high viscosity raw materials,successfully avoiding the lengthy calculation of CFD-DEM coupling simulation to predict the liquid bridge force.Based on the EDEM software platform and the secondary development of C language,the embedded program was developed for the liquid bridge normal force model and the high viscosity contact model of wetting and softening high viscosity fine particles,in which the bidirectional transfer data between model embedding program and EDEM software and the collaborative integration simulation between the mixing process of multi-component raw powder and the process of the agglomeration and granulation of high viscosity spray wetting and softening powder been realized.Based above achievement,the defect that the periodic boundary condition zoning simulation method used abroad cannot reflect the synergistic coupling and coupling effects between the mixing process and agglomeration granulation process of multicomponent raw powder,and technical challenges that EDEM software is unable to locally applying model parameters been solved.By means of simulation,the synergistic coupling evolution law of the key quality attributes of particles-structural characteristics-screw scale-granulating binder characteristics was clarified and its synergistic coupling mechanism was interpreted by means of simulation for D11 small twin screw high shear wet granulation machine.And the positive correlation between the particle size,yield and screw scale is accurately predicted.Small twin screw scale can easily induce a common technical problem of small particle size and low yield,which is consistent with the experimental research results of Osorio.It is proposed to effectively improve the particle size and yield of D11 small twin screw high shear wet granulator by increasing the screw pitch compression ratio of granulator,the liquid bridge normal force and surface energy density of high viscosity wetting and softening fine particles.Research shows that D11 small twin screw high shear wet granulator can manufacture particles with 700 to 1000 μm,which meet R&D objectives. |
