Discrete Element Simulation Of Traditional Chinese Medicine Mixing Proces

The mixing process is one of the common key units in the production of oral solid preparations of traditional Chinese medicine.The consistency of downstream process and final product quality will be affected by the uneven mixing of powder or the remixing or segregation after mixing evenly.At present,the research on the mixing of traditional Chinese medicine focuses on the on-line monitoring technology of mixing uniformity and the judgment of mixing end point,the limitation of sensor monitoring site or artificial sampling position,which results in the researchers unable to obtain sufficient and comprehensive data from the mixer.The lack of research on the mechanism of mixing process and the characteristics of "black box" of mixing process with complex component system of traditional Chinese medicine restrict the progress of equipment and technology of mixing process of traditional Chinese medicine.Discrete element method is a numerical method to calculate the motion of a large number of particles under given conditions,which can realize the numerical simulation of the mechanical characteristics of particulate matter.Discrete element simulation is applied in this paper.Firstly,the calibration model of discrete element simulation parameters is established by using traditional Chinese medicine extract powder and auxiliary materials.After the simulation parameters are determined,the dextrin-baicalin system is used as the research carrier.The discrete element simulation and experimental verification are carried out for the mixture of 50%and 30%.The mixing end point is the same and the RSD(relative standard deviation)of dextrin mass fraction decreases similar,which proves the reliability of discrete element simulation method.Finally,the mixing mechanism of the mixture of Chinese medicine and medicine in the system is investigated by discrete element simulation.The contents of this paper are as follows:1.Study on calibration method of discrete element simulation parameters in mixing process of traditional Chinese medicineDiscrete element method(DEM)determination of angle of repose and bulk density of Chinese herbal extract powder,and compared with the experimental results,so as to determine the contact parameters and solid density between particles and between particles and geometry.6 kinds of powders,including raw licorice extract powder,duhuo extract powder,baicalin powder,micro crystalline cellulose(MCC),ethyl cellulose(EC)and dextrin,are the research objects.Based on the Hertz-Mindlin with JKR Cohesion contact model and particle scaling,by Plackett-Burman design,the contact parameters which have a significant effect on the simulated measurement of angle of repose are selected,and then the optimal area of key contact parameters is determined by steepest climbing design,finally,according to Box-Behnken experimental results,to establish a regression model between the simulated angle of repose and contact parameters,select the best contact parameter value and verify it.After determining the contact parameters,the density parameter calibration model is established by single factor experiment.It turns out,the particle-particle rolling friction coefficient,particle-particle recovery coefficient and particle-stainless steel recovery coefficient are the key contact parameters in discrete element simulation repose angle.The calibration range of the calibration model is 29.11°to 50.11°,the absolute value of relative error between the simulated and experimental values of 6 kinds of powder rest angle is less than 2.0%;density parameter models’R2=0.99,the linear relationship is good,and the absolute error between the simulated and experimental values of six bulk density is less than 5.0%,which indicates that the calibration method is accurate and reliable.Above studies have proved the feasibility of indirectly calibrating the microscopic mechanical parameters DEM traditional Chinese medicine particle system through macroscopic physical parameters,which lays a foundation for accurate simulation of the pharmaceutical process of traditional Chinese medicine such as mixing and transportation.2.The discrete element simulation and experimental study of the mixture of raw and auxiliary materials of traditional Chinese medicineTaking the mixture of dextrin and baicalin powder as an example.A total mixing mass of 200 g,dextrin 50%and 30%mixed,comparing the mixed results of discrete element simulation with real experiments,it is proved that the feasibility of using discrete element simulation to study the mixing of raw and auxiliary materials of traditional Chinese medicine.First,the contact and density parameters of dextrin and baicalin are determined by discrete element simulation parameter calibration model,with the laboratory mixer as a reference,an intermittent mixer with a volume of about 2L,blending speed set to 15 rpm,set mixing time is 1 min.By calculating the mass fraction of dextrin RSD,intercepting the image of the distribution of the material in the mixer and identifying the segregation area in the mixer,found that the RSD value of dextrin mass fraction was smaller when the drug-assisted ratio was 50%,dextrin is more evenly distributed in the mixer,there are more segregation areas in the mixer.After simulating mixing,using the same material,proportion and mixing conditions,3 sampling sites were set up in the mixer at different time points,because the traditional method is difficult to detect dextrin,hence,the mixing effect is evaluated by calculating the RSD value of the characteristic value of the particle size distribution of mixed materials at different sampling sites in the mixer,and compare the experimental results with the simulation results,and it turns out that the simulation and the experiment were mixed at 1 min,and the mixed RSD values of the two have a similar trend.It is proved that discrete element simulation is a reliable method to study the mixing of raw and auxiliary materials of traditional Chinese medicine.3.Study on the mechanism of intermittent mixing under low proportionIt is difficult to accurately detect materials with a low overall proportion,challenges to quality control and research,in order to explore the mixing mechanism when the drug is low,in this study,discrete element simulation,the mixed system of dextrin and baicalin powder was studied.The mixing conditions of dextrin 10%,5%,3%and 1%were set,under the same mixing conditions,dextrin mass fraction RSD values,the results showed that the lower the dextrin ratio,RSD more unstable,and the value is larger at the end of the mixing.Then,the effects of mixing time,material filling level and material filling sequence on mixing and their mechanism are explored.The results show that with the increase of mixing time,dextrin ratio of 1%of the mixed RSD value and change is smaller.When the dextrin ratio was 1%,the RSD value of dextrin mass fraction at 200 g was more stable than that at 100 g and 300 g,and lower at the end of mixing.The filling sequence of dextrin has no obvious effect on the mixing result,but the segregation area in the mixer will be different.Analysis of the movement of dextrin particles in different areas of the mixer found that,the causes of these results are related to convection mixing,free diffusion and mixer construction.It is proved that discrete element simulation is an effective tool to explore mixing mechanism.To sum up,this paper establishes the parameter calibration method and simulation verification method suitable for DEM simulation of traditional Chinese medicine powder system,and studies the mixing mechanism of binary particle system containing traditional Chinese medicine.It provides a new idea for the study of traditional Chinese medicine mixing.