Laboratory of Biophysics and Surface Analysis, School of Pharmacy, University of Nottingham, Nottingham, UK.
Eur J Pharm Biopharm. 2010 Nov;76(3):498-506. doi: 10.1016/j.ejpb.2010.08.006. Epub 2010 Aug 27.
X-ray micro-computed tomography (XMCT) was used in conjunction with confocal Raman mapping to measure the intra-granular pore size, binder volumes and to provide spatial and chemical maps of internal granular components in α-lactose monohydrate granules formulated with different molecular weights of polyvinyl pyrrolidone (PVP). Infrared spectroscopy was used to understand the molecular association of binder domains. Granules were prepared by high-shear aqueous granulation from α-lactose monohydrate and PVP K29/32 or K90. XMCT was used to visualise the granule microstructure, intra-granular binder distribution and measure intra-granular porosity, which was subsequently related to intrusion porosimetry measurements. Confocal Raman microscopy and infrared microscopy were employed to investigate the distribution of components within the granule and explore the nature of binder substrate interactions. XMCT data sets of internal granule microstructure provided values of residual porosity in the lactose:PVP K29/32 and lactose:PVP K90 granules of 32.41 ± 4.60% and 22.40 ± 0.03%, respectively. The binder volumes of the lactose:PVP K29/32 and lactose:PVP K90 granules were 2.98 ± 0.10% and 3.38 ± 0.07%, respectively, and were attributed to PVP-rich binder domains within the granule. Confocal Raman microscopy revealed anisotropic domains of PVP between 2 μm and 20 μm in size surrounded by larger particles of lactose, in both granule types. Raman data showed that PVP domains contained various amounts of lactose, whilst IR microscopy determined that the PVP was molecularly associated with lactose, rather than residual water. The work shows that XMCT can be applied to investigate granular microstructure and resolve the porosity and the excipient and binder volumes. Combining this technique with vibrational techniques provides further structural information and aids the interpretations of the XMCT images. When used complementarily, these techniques highlighted that porosity and binder volume were the most significant microstructural differences between the α-lactose monohydrate granules formulated with the different grades of PVP.
X 射线微计算机断层扫描 (XMCT) 与共聚焦拉曼映射相结合，用于测量颗粒内的孔径、结合剂体积，并提供 α-乳糖一水合物颗粒中内部颗粒成分的空间和化学图谱，这些颗粒是用不同分子量的聚乙烯吡咯烷酮 (PVP) 配制的。红外光谱用于了解结合剂域的分子缔合。颗粒通过高剪切水合作用从 α-乳糖一水合物和 PVP K29/32 或 K90 制备。XMCT 用于可视化颗粒微观结构、颗粒内结合剂分布并测量颗粒内孔隙率，随后将其与压入孔隙率测量相关联。共聚焦拉曼显微镜和红外显微镜用于研究颗粒内成分的分布并探索结合剂基质相互作用的性质。内部颗粒微观结构的 XMCT 数据集提供了乳糖：PVP K29/32 和乳糖：PVP K90 颗粒中残留孔隙率的值分别为 32.41 ± 4.60%和 22.40 ± 0.03%。乳糖：PVP K29/32 和乳糖：PVP K90 颗粒的结合剂体积分别为 2.98 ± 0.10%和 3.38 ± 0.07%，这归因于颗粒内富含 PVP 的结合剂域。共聚焦拉曼显微镜显示，在两种颗粒类型中，大小在 2 μm 到 20 μm 之间的 PVP 存在各向异性域，周围是较大的乳糖颗粒。拉曼数据显示 PVP 域含有不同量的乳糖，而红外显微镜确定 PVP 与乳糖分子结合，而不是与残留水结合。该工作表明，XMCT 可用于研究颗粒微观结构并解析孔隙率以及赋形剂和结合剂体积。将该技术与振动技术结合使用可提供进一步的结构信息，并有助于解释 XMCT 图像。互补使用这些技术突出表明，在与不同等级 PVP 配制的 α-乳糖一水合物颗粒之间，孔隙率和结合剂体积是最重要的微观结构差异。
