Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University, 220 Gung-dong, Yuseung-gu, Daejeon 305-764, Republic of Korea.
Int J Pharm. 2010 Aug 30;396(1-2):239-45. doi: 10.1016/j.ijpharm.2010.06.032. Epub 2010 Jun 25.
The aim of this study was to investigate the effects of micronization and amorphorization of cefdinir on solubility and dissolution rate. The amorphous samples were prepared by spray-drying (SD) and supercritical anti-solvent (SAS) process, respectively and their amorphous natures were confirmed by DSC, PXRD and FT-IR. Thermal gravimetric analysis was performed by TGA. SEM was used to investigate the morphology of particles and the processed particle had a spherical shape, while the unprocessed crystalline particle had a needle-like shape. The mean particle size and specific surface area were measured by dynamic light scattering (DLS) and BET, respectively. The DLS result showed that the SAS-processed particle was the smallest, followed by SD and the unprocessed cefdinir. The BET result was the same as DLS result in that the SAS-processed particle had the largest surface area. Therefore, the processed cefdinir, especially the SAS-processed particle, appeared to have enhanced apparent solubility, improved intrinsic dissolution rate and better drug release when compared with SD-processed and unprocessed crystalline cefdinir due not only to its amorphous nature, but also its reduced particle size. Conclusions were that the solubility and dissolution rate of crystalline cefdinir could be improved by physically modifying the particles using SD and SAS-process. Furthermore, SAS-process was a powerful methodology for improving the solubility and dissolution rate of cefdinir.
本研究旨在探讨头孢地尼的微粉化和非晶化对其溶解度和溶出速率的影响。采用喷雾干燥（SD）和超临界抗溶剂（SAS）法分别制备了无定形样品，并通过差示扫描量热法（DSC）、粉末 X 射线衍射（PXRD）和傅里叶变换红外光谱（FT-IR）确认了其无定形性质。热重分析（TGA）通过 TGA 进行。扫描电子显微镜（SEM）用于研究颗粒的形态，处理后的颗粒呈球形，而未经处理的结晶颗粒呈针状。通过动态光散射（DLS）和 BET 分别测量了平均粒径和比表面积。DLS 结果表明，SAS 处理后的颗粒最小，其次是 SD 和未经处理的头孢地尼。BET 结果与 DLS 结果相同，即 SAS 处理后的颗粒具有最大的表面积。因此，与 SD 处理和未经处理的结晶头孢地尼相比，处理后的头孢地尼，特别是 SAS 处理后的颗粒，由于其无定形性质和减小的粒径，表现出增强的表观溶解度、提高的内在溶出速率和更好的药物释放。结论是，通过使用 SD 和 SAS 工艺对颗粒进行物理改性，可以提高结晶头孢地尼的溶解度和溶出速率。此外，SAS 工艺是提高头孢地尼溶解度和溶出速率的有效方法。
