Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku 142-8501, Tokyo, Japan.
Juntendo University Faculty of Pharmacy, 6-8-1 Hinode, Urayasu 279-0013, Chiba, Japan.
Molecules. 2024 Oct 4;29(19):4704. doi: 10.3390/molecules29194704.
Two ethanol-solvated adipate and succinate salts of carvedilol (CVD), a Biopharmaceutics Classification System class 2 drug, were synthesized by crystallizing ethanol with adipic acid (ADP) and succinic acid (SUA). Proton transfer from ADP and SUA to CVD and the presence of ethanol in the two novel compounds were confirmed using powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and single-crystal X-ray diffraction measurements. The two novel ethanol-solvated salts exhibited enhanced solubility and dissolution rates compared with pure carvedilol in phosphate buffer (pH 6.8). Additionally, the morphologies and attachment energies of the two novel compounds and pure CVD were calculated based on their single-crystal structures, revealing a correlation between attachment energy and dissolution rate.
两种乙醇溶剂化的卡维地洛（CVD）己二酸和琥珀酸盐（CVD），一种生物药剂学分类系统（BCS）分类为 2 类药物，通过与己二酸（ADP）和琥珀酸（SUA）共结晶乙醇合成。通过粉末 X 射线衍射、傅里叶变换红外光谱、差示扫描量热法、热重分析和单晶 X 射线衍射测量，证实了 ADP 和 SUA 向 CVD 的质子转移以及两种新化合物中乙醇的存在。与纯卡维地洛相比，两种新型乙醇溶剂化盐在磷酸盐缓冲液（pH 6.8）中表现出更高的溶解度和溶解速率。此外，根据它们的单晶结构计算了两种新型化合物和纯 CVD 的形态和附着能，揭示了附着能与溶解速率之间的相关性。
