Quantitative Analysis Of Single Particle Structures Of Microcrystalline Celluloses And Its Effects On Tablet Disintegration

The powder properties of the pharmaceutical excipients affect the quality of the formulation product. There are significant differences in the micro-3D (Dimension) structure.The variant microstructure of the of a single particle is directly related to the intrinsic differences in their adjuvants, which in turn affect their powder as well as tableting properties.The intrinsic quality of the formulation is dependent on the structure of its excipients. In the process of preparation, the powder structure of the adjuvant affects the structure of the preparation. Likewise, the quality of the formulation determines the overall efficacy of drugs,regarding its disintegration properties, drug release characteristics and release mechanism.The main research of this thesis is based microstructure analysis of microcrystalline cellulose (MCC) products during their disintegration process which are obtained from different manufacturers. The microstructure and properties of single particles were quantitatively studied by Synchrotron Radiation X-ray micro Computed Tomography(SR-νCT). Combined with Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLSDA), voids difference, powder properties and formulation behavior, quantitative study of the microstructure of the particles and the nature of the relationship between the materials were studied quantity. So, classification of the MCC single particle was studied for determining the different manufacturers and different specifications of the product differences. After tableting, the 2D and 3D structure were analyzed by SR-μCT on a single particle scale. PCA and PLSDA were used to correlate the single particle structure with porosity variation, powder properties and formulation behavior of MCC. The morphological disintegration model was observed to be as two mechanistic types: laminating types and splitting types. Finally, parameter trend analysis for the relationship between the single particle morphology and the tablet structure were analyzed. The properties of the pharmaceutical excipient powder, the tableting behavior and the disintegration structure of the tablet were also determined.The main research contents are as follows:(1) Microstructure of microcrystalline cellulosesThe microstructure of the microcrystalline cellulose was characterized by its adjuvant powder. The structure of the single particle was characterized and correlated by SR-μCT,together with PCA and PLSDA. The particle properties of the MCC tablets were measured by scanning electron microscopy, SR-μCT, angle of repose, bulk density, tapped density and compression properties, as well as tensile strength, disintegration time and radial force-displacement distribution. The structure of MCC particles and the relationship between structure and properties were analyzed on the basis of 2D slices and 3D reconstruction graphics processing and PCA-PLSDA method. The results showed that there is a significant difference in the tensile strength, disintegration time, the Kawakita plot and the radial pressure-displacement distribution of the tablet. The ratio of the box and the Feret and other structural parameter had a great influence on the classification of the principal component, but the angle of repose and the density has no significant effect. These findings confirm that MCC samples from different manufacturers had morphological diversity at a single particle level,resulting in differences in powder properties as well as tablet properties.(2) Study on the structure and disintegration pattern of microcrystalline celluloseBy investigating the disintegration patterns of 12 types of MCC, combined with the results of microfluidic imaging of tablets, the internal porosity of single particles was calculated for multivariate analysis of its structure in multiple dimensions. The SR-μCT and data graph processing techniques were used to study the 2D axial and radial slice and 3D microporous structure analysis. Based on the comprehensive analysis of PCA and PLSDA, a novel disintegration model was observed to be varied from classical mechanism of morphological disintegration model, such as laminating types and splitting types disintegration model. Finally, the trend of single particle and formulation parameters were analyzed at the 3D level. The single particle morphology and the tablet structure were correlated and the factors affecting the structure of particles during their disintegration were identified.In this paper, the quantitative analysis of MCC particle structure was firstly performed at the single particle level to evaluate its internal structure that is associated with the structural differences as well as the nature of powder and preparation. At the level of tablet, the morphological disintegration patterns of the tablets were analyzed by two types of morphological disintegration patterns, called laminating tablets types and splitting tablets types. Finally, the tendency of single particle and tablet parameters was analyzed at the 3D level, and the relationship between the single particle morphology and the tablet structure was performed. The properties of the powder and the disintegration structure of the tablet were also determined. All in all, there are quantitative relationships among single particle morphology, the tablet structure and morphological disintegration patterns.