Zhang Liu, Shakya Shailendra, Wu Li, Wang Jiangtao, Jin Guanghui, Sun Huimin, Yin Xianzhen, Sun Lixin, Zhang Jiwen
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Asian J Pharm Sci. 2020 Jan;15(1):60-68. doi: 10.1016/j.ajps.2019.01.001. Epub 2019 Mar 1.
The shapes of particles and their distribution in tablets, controlled by pretreatment and tableting process, determine the pharmaceutical performance of excipient like lubricant. This study aims to provide deeper insights to the relationship of the morphology and spatial distribution of stearic acid (SA) with the lubrication efficiency, as well as the resulting tablet property. Unmodified SA particles as flat sheet-like particles were firstly reprocessed by emulsification in hot water to obtain the reprocessed SA particles with spherical morphology. The three-dimensional (3D) information of SA particles in tablets was detected by a quantitative and non-invasive 3D structure elucidation technique, namely, synchrotron radiation X-ray micro-computed tomography (SR-µCT). SA particles in glipizide tablets prepared by using unmodified SA (GUT), reprocessed SA (GRT), as well as reference listed drug (RLD) of glipizide tablets were analyzed by SR-µCT. The results showed that the reprocessed SA with better flowability contributed to similarity of breaking forces between that of GRT and RLD. SA particles in GRT were very similar to those in RLD with uniform morphology and particle size, while SA particles in GUT were not evenly distributed. These findings not only demonstrated the feasibility of SR-µCT as a new method in revealing the morphology and spatial distribution of excipient in drug delivery system, but also deepened insights of solid dosage form design into a new scale by powder engineering.
颗粒的形状及其在片剂中的分布受预处理和压片过程控制，决定了润滑剂等辅料的药学性能。本研究旨在深入了解硬脂酸（SA）的形态和空间分布与润滑效率以及由此产生的片剂性质之间的关系。未改性的SA颗粒为扁平片状颗粒，首先通过在热水中乳化进行再加工，以获得具有球形形态的再加工SA颗粒。通过一种定量且非侵入性的三维（3D）结构解析技术，即同步辐射X射线微计算机断层扫描（SR-µCT），检测片剂中SA颗粒的三维信息。通过SR-µCT分析了使用未改性SA（GUT）、再加工SA（GRT）制备的格列吡嗪片剂以及格列吡嗪片剂的参比上市药品（RLD）中的SA颗粒。结果表明，流动性更好的再加工SA有助于GRT和RLD之间的断裂力相似。GRT中的SA颗粒与RLD中的SA颗粒非常相似，形态和粒径均匀，而GUT中的SA颗粒分布不均匀。这些发现不仅证明了SR-µCT作为一种揭示药物递送系统中辅料形态和空间分布的新方法的可行性，还通过粉末工程将固体制剂设计的见解深化到了一个新的层面。
