文献类型：期刊文献

英文题名：Screen for Inhibitors of Crystal Growth to Identify Desirable Carriers for Amorphous Solid Dispersions Containing Felodipine

作者：Fu, Jinping[1];Cui, Lin[1];Yang, Congbin[1];Xiong, Hui[1];Ren, Guobin[1];Ma, Xingyuan[2];Jing, Qiufang[1];Ren, Fuzheng[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Lab Pharmaceut Crystal Engn & Technol, 363,130 Meilong Rd, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, Shanghai 200237, Peoples R China

年份：2018

卷号：19

期号：3

起止页码：1231

外文期刊名：AAPS PHARMSCITECH

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000428932700026)】；

基金：This work was supported by the Baoshan District Committee of Science and Technology (grant no. bkw2014131) and the National Natural Science Foundation of China (grant no. 21576080).

语种：英文

外文关键词：felodipine; zein; inhibitory effect on crystal growth; solid dispersions; intermolecular interactions

摘要：The solvent-shift method was used to identify appropriate polymers that inhibit the growth of felodipine crystals by monitoring particle size in supersaturated drug solutions in the presence of different polymers. We speculated that there would be an intermolecular interaction between the selected polymer (zein) and felodipine by extrapolating the inhibitory effect on crystal growth and then used the selected polymer as a carrier to prepare solid dispersions. The formulations were characterized by crystalline properties, thermodynamics of mixing, dissolution behavior, and physical stability. Powder x-ray diffraction and differential scanning calorimetry experiments indicated that amorphous solid dispersions were formed when the proportion of felodipine was < 30% (w/w). Stability tests showed that a solid dispersion with 20% felodipine remained in an amorphous state and was stable under accelerated storage conditions for 6 months. The dissolution rates of solid dispersions were significantly greater than those of the active pharmaceutical ingredient or physical mixtures. Analysis by Fourier-transform infrared spectroscopy and Raman microspectroscopy indicated the formation of intermolecular interactions between zein and felodipine. The study demonstrates the successful application of the chosen polymer as a carrier in solid dispersions and validates the concept of extrapolating the inhibitory effect on crystal growth to intermolecular interactions.