Jelcic Z, Hauschild K, Ogiermann M, Picker-Freyer K M
PLIVA-Research and Development Ltd., Pharmaceutical Technology, Prilaz baruna Filipovica, Zagreb, Croatia.
Drug Dev Ind Pharm. 2007 Apr;33(4):353-72. doi: 10.1080/03639040701199241.
The aim of this study was to use 3D modeling to differentiate not only among the four different types of lactose alpha-lactose monohydrate, spray-dried lactose, agglomerated lactose and lactose anhydrous but also between products from different manufacturers. Further "box-counting" fractal analysis of SEM images was done to gain additional information on tableting characteristics and tablet properties which can be found in the fractal structure. Twelve different materials from different manufacturers were analyzed for their powder-technological and physicochemical properties. They were tableted on an eccentric tableting machine at graded maximum relative densities and the recorded data, namely force, time, and displacement were analyzed by the 3D modeling technique. Tablet properties such as, elastic recovery, crushing force and morphology were analyzed. The results show that 3D modeling can precisely distinguish deformation behavior for different types of lactose and also for the same type of material produced with a slightly different technique. Furthermore, the results showed that the amorphous content of the lactose determined the compactibility of the material, which is due to a reversible exceeding of the glass transition temperature of the material. The three fractal dimensions DBW (box surface dimension), DWBW (pore/void box mass dimension), and DBBW (box solid mass dimension) are capable of describing morphological differences in lactose materials. Multivariate regression analysis showed that the fractal surface structure of the lactose-based materials is strongly correlated to tableting characteristics and tablet properties. Especially with regards to 3D modeling, it was found that the fractal indices can describe the parameters time plasticity d, pressure plasticity e, and fast elastic decompression, which is the inverse of omega. In addition, the 3D parameters are able to describe the powder and tablet fractal indices. In conclusion, the 3D modeling is not only able to characterize the compression process but it can also provide information on the final tablet morphology.
本研究的目的是利用三维建模不仅区分四种不同类型的乳糖——一水合α-乳糖、喷雾干燥乳糖、附聚乳糖和无水乳糖，而且区分不同制造商生产的产品。对扫描电子显微镜（SEM）图像进行进一步的“盒计数”分形分析，以获取有关压片特性和片剂性质的更多信息，这些信息可以在分形结构中找到。分析了来自不同制造商的12种不同材料的粉末工艺和物理化学性质。它们在偏心压片机上以分级最大相对密度压片，并通过三维建模技术分析记录的数据，即力、时间和位移。分析了片剂性质，如弹性恢复、压碎力和形态。结果表明，三维建模能够精确区分不同类型乳糖的变形行为，也能区分采用略有不同技术生产的同一类型材料的变形行为。此外，结果表明，乳糖的无定形含量决定了材料的可压性，这是由于材料的玻璃化转变温度可逆性地超过所致。三个分形维数DBW（盒表面维数）、DWBW（孔隙/空隙盒质量维数）和DBBW（盒固体质量维数）能够描述乳糖材料的形态差异。多元回归分析表明，基于乳糖的材料的分形表面结构与压片特性和片剂性质密切相关。特别是关于三维建模，发现分形指数可以描述参数时间可塑性d、压力可塑性e和快速弹性解压，后者是ω的倒数。此外，三维参数能够描述粉末和片剂的分形指数。总之，三维建模不仅能够表征压缩过程，还能够提供有关最终片剂形态的信息。
