Design,Tableting Performance Improvements,and Mechanism Analysis About TCM-Based Composite Particles

Objective:This study aimed to?i?evaluate the current situation of direct compaction?DC?for Traditional Chinese Medicine?TCM?powders;?ii?design and prepare composite particles?CPs?to improve the compactibility and flowability of TCM powders with fluid-bed coating;?iii?analyze the improvement mechanism;?iv?optimize the design of TCM-based CPs;and?v?promote the application of DC in production of TCM tablets.Methods:?1?27 kinds of TCM powders were chosen based on their preparation method?i.e.,ethylalcohol extraction,water extraction,or direct pulverization?and medicinal part category.Their micromeritic properties were evaluated comprehensively,and their applicability for DC was analyzed through multiple statistical analysis methods.?2?For each preparation method,a representative TCM powder?i.e.,ethylalcohol extracted powder of Zingiberis Rhizoma,water extracted powder of Gardeniae Fructus,or direct pulverization powder of Poria?was selected as the model drug,which was fluid bed coated with eight kinds of modifiers?HPMC,Dextran,Inulin,PVP,PVP+Mannitol,PVP+Si O₂,HPMC+Mannitol,and HPMC+Si O₂?to prepare CPs,respectively.On the other hand,the physical mixtures?PMs?with same formulations were prepared by physical mixing and used as the control group.The powder properties of the materials were comprehensively characterized from the molecular,granular,powder,and tableting levels in order to analyze the improvement mechanism and compare the different influences of the modifiers on the compactibility and flowability of CPs.?3?For each preparation method,three representative TCM powders were selected to prepare CPs with two representative modifiers?i.e.,HPMC and PVP?by fluid bed coating,respectively.The powder properties and compaction parameters of materials were comprehensively characterized to further compare the effects of HPMC and PVP on the DC properties of TCM-based CPs.?4?The extracted powder of Andrographis herba?AHE?was developed to directly compactible powders by fluid bed coating with 6%to 12%HPMC based on particle engineering.The process-,instrument-,and formulation-related variables of the coating process were simultaneously optimized with the Hunter L18 screening design.Yield?Y1?,compactibility?Y2?,and angle of repose?Y3?were measured as the responses.The optimized CP was mixed with the DC-grade excipient?lactose,microcrystalline cellulose,or home-made mannitol?or other TCM-based CPs with different ratios to produce tables by continuous DC.Tablets were selected randomly to determine the relevant properties.Results:?1?First,81.5%of the 27 kinds of TCM powders chosen exhibited both poor compactibility and flowability,and none of the TCM powders could be compacted into tablets via DC.Second,the micromeritic properties of TCM powders prepared by direct pulverization were significantly different from those of extracted ones,while there were no significant differences between the water and ethylalcohol extracted ones.Third,the DC properties of TCM powders could be improved through controlling some fundamental properties reasonably.?2?First,the DC properties of TCM powders could be effectively improved by fluid bed coating with the modifiers chosen,and qualified tablets with high drug loadings were successfully produced via continuous DC.Second,fluid bed coating was not a simple process of superposition and transmission of the physical properties of raw materials.The surfaces of TCM particles were effectively coated with the modifiers.This changed the particle structure and surface morphology of TCM powders,thus improving the fundamental properties and DC properties of TCM powders.Overall,HPMC and PVP exhibited superior performances among the eight modifiers studied,so they were further investigated.?3?First,there were no significant differences between the influence of HPMC and PVP on the true density and flowability of CPs.Second,compared with the CPs containing PVP,CPs containing HPMC exhibited larger particle size,more uniform particle size distribution,and smaller bulk density,tapped density,and hygroscopicity.Third,for the ethylalcohol extracted powders,the compactibility of CPs containing HPMC was similar with that of CPs containing PVP;while for the water extracted and direct pulverization powders,the compactibility of CPs containing HPMC was generally higher than that of CPs containing PVP.?4?The optimized variables for preparation of AHE-based CPs were 50 ^oC for inlet air temperature,150 m³/h for inlet airflow,6.5 rpm for binder feed rate,1.2 bar for spray atomisation pressure,L3 for air distributor plate,1.5 cm for the distance between the air distributor plate and the bottom of guide cylinder,6%for the ratio of HPMC to AHE,and 16%for the concentration of coating solution.The small errors?0.51%for Y1,3.17%for Y2,and 4.78%for Y3?between the experimental values?three batches?and the predicted values indicated the high degrees of prediction.Tablets produced with the mixture of the optimized CP and DC-grade excipients/other CPs were qualified.Conclusion:TCM powders commonly exhibit poor DC properties,and these poor properties can be effectively improved to meet the requirements of DC by fluid bed coating with suitable modifiers.On the other hand,TCM-based CPs can be effectively optimized by the Hunter L18 screening design,and the optimized CP exhibits excellent DC applicability.Overall,this study provides some theoretical bases for the development of DC in TCM,and is significant in facilitating the development and modernization of TCM tablets through DC.