Physical Attribute Characterization And Discrete Element Simulation Of Microcrystalline Cellulose

Tablet is the most widely used pharmaceutical dosage form for compression molding of multi-particulate system.Microcrystalline cellulose（MCC）is a commonly used pharmaceutical excipient in the process of tablet compression molding.However,the compaction process seems to be simple,but it is actually affected by complex factors including material types,material properties and force properties.The current common trial-and-error and empirical phenomenological research methods can only summarize experimental facts and draw corresponding laws.There is still a lack of systematic understanding of the evolution law and formation mechanism of the internal microstructure.This subject adopts discrete element method,combined with physical experiments,analyzes the quality difference of MCC from different dimensions,and analyzes the reasons for the difference in fluidity and compaction of MCC from the microscopic angle of force chain strength and distribution,so as to improve our understanding of the film.The cognitive level of preparation quality is helpful to provide a theoretical basis for the selection of preparation excipients.The main research contents are as follows:First,by characterizing the physical quality properties of different types of MCC,the differences in physical and chemical properties were studied.The results show that there is no significant difference in the structure and crystal form of different types of MCC,but the particle size is quite different.There was no significant difference in the appearance and morphology of MCC,among which SH-200 aggregates were more.The hygroscopicity of MCC is related to the particle size,and the smaller the particle size,the faster the moisture absorption rate.The compressibility and angle of repose of different types of MCC are significantly different,among which SH-200 has the smallest compressibility（25.0 8%）and angle of repose（32.83°）,indicating that it has good fluidity.Different types of MCC show better compressibility,and SH-200 is the best.To sum up,different types of MCC have significant differences in quality attributes such as particle size,hygroscopicity,powder fluidity and compressibility.Secondly,based on the angle of repose to characterize the fluidity index,combined with physical experiments and DEM simulations,the relationship between microscopic and macroscopic quality attributes was constructed.Taking the angle of repose（θ）of the lifting cylinder method as the response value,the simulation parameters were screened and optimized through experimental design.0.79),SH-102B（0.71,0.73,0.87）,the parameters are robust and reliable.When the lifting speed of the lifting cylinder method and the funnel height of the funnel injection method are within a certain range（～2.5m/s,～35mm）,the angle of repose does not change significantly.The detection method and the reasons for the influence of human factors on the angle of repose of the same detection method.In summary,the microscopic parameters（friction coefficient,rolling damping coefficient）of MCC particles calibrated by DEM have a good correlation with the macroscopic mass properties（angle of repose）.The smaller the angle of repose,the better the fluidity and the smaller the friction.Finally,based on the parameters calibrated by the angle of repose,the process of MCC powder compaction and tensile strength was further simulated and studied,and the evolution law of its force chain was analyzed.Taking the actual values of pressure and tensile strength as the target,the regression equation is solved,and the optimal parameter combination（X₁,X₃,X₉）is obtained:SH-200(6.63×10⁵N/m,8.97×10⁹N/m,The verification parameters are reliable.The distribution of the force chain network at the compression lowest point of different sheet thicknesses and the splits is extracted.The results show that the direction of the force chain is consistent with the direction of the loading force.When splitting,the force chain at the gap is stronger than other force chains around it;the longer the compression distance,the stronger the force chain.The tighter the chain network,on the contrary,the looser the force chain network.