Impact of Particle Size on Density of Binary Powder Mixture of Chinese Medicine / 中国实验方剂学杂志

Objective:To investigate the influence of particle size on density of binary powder mixture of traditional Chinese medicine （TCM）， and to provide reference for formulation design of TCM preparations. Method:Three groups of binary powder mixtures with different particle size ratio （<italic>α</italic>） were constructed， namely Oroxyli Semen-microcrystalline cellulose PH102 （MCC PH102） （<italic>α</italic>=0.071 7）， Stellariae Radix-MCC PH200 （<italic>α</italic>=0.158 7） and Angelicae Sinensis Radix-MCC KG802 （<italic>α</italic>=0.840 6）. Binary powder mixtures with nine mass ratios （90∶10， 80∶20， 70∶30， 60∶40， 50∶50， 40∶60， 30∶70， 20∶80 and 10∶90） were prepared for each group， and 27 binary powder mixtures containing TCM were obtained. The particle size distribution， density and other parameters of six single materials and 27 binary powder mixtures were characterized. Based on the packing theory and multivariate analysis， the effects of particle size related parameters on the filling structure and density of the binary powder mixtures were elucidated. Result:The <italic>α</italic> of Angelicae Sinensis Radix-MCC KG802 binary mixture system was larger than the replacement rate （<italic>α</italic>_r=0.741 0）， and its density had a good linear relationship with the mass ratio， which conformed to the replacement mechanism. The <italic>α</italic> of Oroxyli Semen-MCC PH102 binary mixture system was smaller than the critical ratio （<italic>α</italic>_c=0.154 0）， and its density was nonlinear with the mass ratio of components， which conformed to the filling mechanism. The <italic>α</italic> of Stellariae Radix-MCC PH200 binary mixture system was between <italic>α</italic>_c and <italic>α</italic>_r， its density was affected by both of replacement mechanism and filling mechanism. Based on the partial least squares （PLS） model， the variable importance in the projection （VIP） analysis further proved that the mixing mass ratio （VIP value=1.62）， <italic>α</italic> （VIP value=1.13） and <italic>D</italic>₁₀ （the corresponding particle size when the particle size distribution accumulated to 10%， VIP value=1.06） were the key factors affecting the density of binary powder mixtures of TCM. Conclusion:In the binary powder mixtures of TCM， the linearity relationship between density and mass ratio is largely depended on particle size difference of components.

Material manufacturability classification in high shear wet granulation process of Chinese medicine / 中国中药杂志

The high shear wet granulation(HSWG) process of Chinese medicine has a complicated mechanism. There are many influencing factors that contribute to this process. In order to summarize the manufacturability of different kinds of materials in HSWG, this paper constructed a material library composed of 11 materials, including 4 Chinese medicine extracts and 7 pharmaceutical excipients. Each material was described by 22 physical parameters. Several binders were employed, and their density, viscosity and surface tension were characterized. Combining empirical constraints and the principle of randomization, 21 designed experiments and 8 verification experiments were arranged. The partial least squares(PLS) algorithm was used to establish a process model in prediction of the median granule size based on properties of raw materials and binders, and process parameters. The surface tension and density of binders, as well as the maximum pore saturation were identified as key variables. In the latent variable space of the HSWG process model, all materials could be divided into three categories, namely the Chinese medicine extracts, the diluents and the disintegrants. The granulation of Chinese medicine extracts required low viscosity and low amount of binder, and the resulted granule sizes were small. The diluent powders occupied a large physical space, and could be made into granules with different granule sizes by adjusting the properties of binders. The disintegrants tended to be made into large granules under the condition of aqueous binder. The combination use of material database and multivariate modeling method is conducive to innovate the knowledge discovery of the wet granulation process of Chinese medicine, and provides a basis for the formulation and process design based on material attributes.