基于物料粉体学性质对5种制剂品种颗粒溶化性的相关性研究

Study on correlation of particle solubility of five kinds of preparation based on material powder science

目的以杏贝止咳颗粒(Xingbei Zhike Keli,XZK)、桂枝茯苓胶囊(Guizhi Fuling Jiaonang,GFJ)、天舒胶囊(Tianshu Jiaonang,TJ)、腰痹通胶囊(Yaobitong Jiaonang,YJ)与参乌益肾片(Shenwu Yishen Pian,SYP)5个品种的中间体粉末及颗粒为研究对象,研究中间体粉体学性质与颗粒溶化性的相关性,筛选出影响颗粒溶化性的关键物料属性,为提升产品质量属性提供参考。方法通过对5个品种各20批粉末及颗粒取样,以物料粉体的休止角(α)、松密度(D_(a))、振实密度(D_(c))、孔隙率(I_(e))、卡尔指数(IC)、豪斯纳比(IH)、含水量(HR)、吸湿性(H)、粒径(D_(10)、D_(50)、D_(60)、D_(90))、均匀性(UN)、比表面积(SSA)、相对均齐度(Iθ)、分布范围(span)、宽度(width)、粒径<50μm百分比(Pf)为自变量,中间体颗粒溶化率(DR)为因变量构建关联模型,并以物理指纹图谱与热点图分别对各品种批次间及品种间物理属性相关性进行分析,结合多元统计分析方法研究中药物料粉体学与颗粒溶化性的相关性。结果对所绘制雷达图进行相似度分析,XZK混合粉相似度为86.52%~99.92%,GFJ、TJ软材细粉相似度分别为90.38%~99.97%、89.79%~99.99%,YJ喷干细粉相似度为87.98%~99.90%,SYP干膏粉相似度为86.94%~99.97%;品种间物性参数相关性矩阵热点图显示,各品种指标间相关系数为-0.964~0.998,且在D_(a)、D_(c)、I_(e)、IC、IH、HR、Iθ及span上存在较高相似性,在α与粒径分布范围上存在差异性。主成分分析(principal component analysis,PCA)提取了2个主成分,主成分1主要由IC、IH、SSA及代表粒径性质的D_(10)、D_(50)、D_(60)、D_(90)与Iθ、width、Pf构成,解释率达到57.06%;主成分2由α、D_(a)、D_(c)、I_(e)、HR及UN、span组成,解释率达到20.76%。偏最小二乘回归分析(partial least squares regression analysis,PLS)结果显示,对DR影响显著的是D_(c)、H、SSA、HR、IH、I_(e)及IC。结论运用数据统计分析方法所建立的模型可以较好地预测中间体影响颗粒溶化性的关键物料属性,通过控制相关属性指标来达到改善颗粒生产中出现的析出、焦屑、结块等溶化性问题。

Objective Five varieties of intermediate powder and particles of Xingbei Zhike Keli(XZK,杏贝止咳颗粒),Guizhi Fuling Jiaonang(GFJ,桂枝茯苓胶囊),Tianshu Jiaonang(TJ,天舒胶囊),Yaobitong Jiaonang(YJ,腰痹通胶囊)and Shenwu Yishen Pian(SYP,参乌益肾片)were used as the research objects to study the correlation between intermediate powder properties and particle solubility,and the key material properties affecting the solubility of the preparation were selected to provide reference for improving quality properties of product.Methods The correlation model was constructed by sampling 20 batches of powder and particles of five varieties,with angle of repost(α),bulk density(D_(a)),vibration density(D_(c)),porosity(I_(e)),Carr index(IC),hausner ratio(IH),water content(HR),hygroscopicity(H),particle size(D_(10),D_(50),D_(60),D_(90)),uniformity(UN),specific surface area(SSA),relative homogeneity(Iθ),distribution range(span),width,particle size<50μm percentage(Pf)of the material powder as independent variables and the dissolution rate(DR)of intermediate particles as dependent variable.Physical fingerprint and hot spot maps were used to analyze the correlations of physical properties between batches and varieties.Combined with multivariate statistical analysis method,the correlation between powder chemistry and particle solubility of traditional Chinese medicine preparation was studied by multivariate statistical analysis.Results The similarity analysis of the radar diagram showed that the similarity of XZK mixed powder was 86.52%-99.92%,and the similarity distribution of GFJ and TJ soft material was 90.38%-99.97%and 89.79%-99.99%,respectively.The range of YJ spray dried fine powder similarity was 87.98%-99.90%,and that of SYP dry cream powder was 86.94%-99.97%.The results of the heat map of the correlation matrix of physical parameters among varieties showed that the correlation coefficients of each index were in the range of−0.964-0.998.There were high similarities in D_(a),D_(c),I_(e),IC,IH,HR,Iθand span,but there were differences in theαand particle size distribution range.Two principal components were extracted by principal component analysis(PCA).Principal component 1 was mainly composed of IC,IH,SSA,D_(10),D_(50),D_(60),D_(90),Iθ,width and Pf,and the interpretation rate was 57.06%.Principal component 2 was composed ofα,D_(a),D_(c),I_(e),HR,UN and span,and the interpretation rate reached 20.76%.Partial least squares regression analysis(PLS)showed that D_(c),H,SSA,HR,IH,I_(e),and IC had significant effect on DR.Conclusion The model established by data statistical analysis can predict the key material properties of intermediates that affect the solubility of particles and improve the solubility problems such as precipitation,coke chips,and caking in the preparation production by controlling the related property indexes.