Discrete Element Modeling And Numerical Simulation For The Coating Process Of Non-spherical Tablets

Tablets are usually spray-coated in the pharmaceutical industry,which has a significant impact on the quality of tablet.In the coating process of tablets,the coating uniformity of the final product is difficult to control due to the influence of coating process parameters,equipment structure parameters,drug dosage forms and other factors,and may lead to the reduction of coating process efficiency,changes in the dissolution of active pharmaceutical ingredients,and a variety of potential drug quality problems.In order to avoid the above problems,numerical simulation studies of tablet coating process can be carried out to enhance the understanding of the relationship between equipment structure,process parameters,drug dosage form and final coating uniformity,which is of great significance for optimizing the coating process and improving the quality of tablets.In the discrete element method(DEM)of tablet coating process,the accurate modeling of tablets,the calculation method and modeling of inter-tablet coating uniformity and intra-tablet coating uniformity are the difficulties and keys in the numerical simulation of coating.Therefore,in this paper,the numerical simulation of tablet coating process is carried out from the above mentioned difficulties.The specific research work includes the following aspects:(1)Multi-super-ellipsoid approach is proposed to accurately describe tablets,and the accuracy of the model is verified.With this model,non-spherical particles are modeled by connecting a certain number of super-ellipsoids,and the component super-ellipsoids can overlap with each other.Some non-spherical particles,such as biconvex tablets and capsules,can be described accurately by the multi-super-ellipsoid model.The contact detection between two multi-super-ellipsoid particles is based on the contact detection between their sub particles.Except that,two level local coordinate systems need to be introduced to describe a multi-super-ellipsoid particle in the global coordinate.The first level local coordinate system is introduced to define the location and orientation of the composite particle in the global coordinate system,and the second level local coordinate system is introduced to define the relative position and orientation of each component particle within the composite particle.For multi-super-ellipsoid approach,the mass 8)and the inertia tensor I of the particle can be obtained by the partitioned integral method.At last,in order to verify the accuracy of the multi-super-ellipsoid model,four kinds of non-spherical particles including three kinds of biconvex tablets and one kind of capsule,are adopted in this research.The packing of four kinds of non-spherical particles in a cylinder container and the flow of three kinds of tablets in a horizontal rotating drum are done by both numerical simulation and experiment,and the simulation results are compared with the corresponding experiments.(2)The comparative study of modeling tablets using multi-sphere approach,multi-superellipsoid approach,and polyhedron approach is done to verify the benefits of the multi-superellipsoid approach.The numerical simulation results of multi-sphere approach,multi-super-ellipsoid approach,and polyhedron approach are compared with the results of packing experiment,heap forming experiment,and the flow in a rotating drum to verify the accuracy and computational efficiency of each non-spherical particle shape representation approach in DEM simulation.The final results show that the multi-super-ellipsoid approach is a non-spherical particle representation method that meets the requirements for accuracy and efficiency in tablet simulation.(3)The multi-super-ellipsoid approach is applied for the investigation of the inter-coating uniformity.In this study,discrete element method-discrete droplet method(DEM-DDM)is applied for the investigation of the coating process,tablets are described by different particle shape representation approaches,and the influence of different particle shape models on inter-tablet coating uniformity is investigated.The proposed model is verified by a lab-scale coating experiment within a coating pan firstly.It is clear that multi-super-ellipsoid approach can be used for the investigation of tablet coating,in which the calculation accuracy is relatively high and the computational efficiency is relatively cost-effective.And then,the coating process in a coating drum with baffles is investigated.The influence of different parameters on inter-tablet coating uniformity is also studied,including the droplet diameter,the drum rotation speed,the spray range angle,and the nozzle number,which can provide guidance for the tablet coating process.(4)Two particle surface-based meshing methods are proposed and applied to the simulation study of intra-tablet coating uniformity.Two meshing methods are applied to discretize the surface of the particles,including the strip mesh method and the polyhedral mesh method.The intra-tablet coating uniformity of each single tablet during the coating process is investigated by the tablet meshing method and combining the DEM-DDM with multi-super-ellipsoid model.The validity of the model is first verified by qualitative comparison with theoretical values as well as experiments of other literature,then the effect of different tablet shapes on the intra-tablet coating uniformity is investigated,and the effects of different coating parameters on the intra-tablet coating uniformity are investigated,such as droplet diameter,spray center angle,and drum rotation speed.(5)The combined multi-super-ellipsoid-based DEM-DDM numerical simulation method proposed in this paper is applied to the scaling-up study of the coating process,and the coating process at three scales: bentch scale,pilot scale,and industrial scale,respectively,combined with two mechanistic models for scale-up including equal Froude number and equal linear velocity,and the coating process at different scales is studied numerically.By analyzing the changes of tablet motion behavior,coating results,and collision behavior in the coating drum at different scales,the influence of the scaling-up process on the coating process was analyzed to provide theoretical references for the actual coating production.