Tanida Satoshi, Yoshimoto Aika, Yoshida Miyabi, Uchiyama Hiromasa, Kadota Kazunori, Tozuka Yuichi
Osaka University of Pharmaceutical Sciences.
Chem Pharm Bull (Tokyo). 2019;67(9):921-928. doi: 10.1248/cpb.c18-00644.
We studied the possibility of using ursodeoxycholic acid (UDCA) as an excipient to create an amorphous composite that can be administered to animals in preclinical studies of experimental drugs. Three UDCA-based amorphous samples composed of nifedipine (NIF), indomethacin (IND), and naproxen (NAP) were found by screening. The UDCA-based formulations were adjudged amorphous by solid-state analysis using X-ray powder diffraction and differential scanning calorimetry. In addition, amorphous samples of NIF-UDCA, IND-UDCA, and NAP-UDCA did not crystallize while in 1% methyl cellulose (MC) solution for 120 min, although an amorphous solid dispersion of NIF-poly(vinylpyrrolidone) (PVP) crystallized rapidly. The low hygroscopicity of UDCA helps NIF maintain an amorphous state in 1% MC solution. The UDCA-based amorphous composites can be administered as suspended formulations to animals in preclinical studies.
我们研究了使用熊去氧胆酸（UDCA）作为辅料来制备一种无定形复合材料的可能性，该复合材料可用于实验药物临床前研究中的动物给药。通过筛选，发现了由硝苯地平（NIF）、吲哚美辛（IND）和萘普生（NAP）组成的三种基于UDCA的无定形样品。通过使用X射线粉末衍射和差示扫描量热法进行固态分析，判定基于UDCA的制剂为无定形。此外，NIF-UDCA、IND-UDCA和NAP-UDCA的无定形样品在1%甲基纤维素（MC）溶液中放置120分钟时未结晶，而NIF-聚（乙烯基吡咯烷酮）（PVP）的无定形固体分散体则迅速结晶。UDCA的低吸湿性有助于NIF在1% MC溶液中保持无定形状态。基于UDCA的无定形复合材料可在临床前研究中作为混悬制剂给予动物。
