文献类型：期刊文献

英文题名：Investigating molecular interactions of high-loaded glipizide-HPMCAS microparticles by integrated experimental and modeling techniques

作者：Li, Qiang[1];Zhao, Qianqian[2];Jing, Qiufang[1];Ma, Xiaosi[1];Chen, Ning[1];Ren, Guobin[1];Ouyang, Defang[2];Ren, Fuzheng[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[2]Univ Macau, ICMS, State Key Lab Qual Res Chinese Med, Taipa, Macao, Peoples R China

年份：2019

卷号：131

起止页码：127

外文期刊名：EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000460399800014)】；

基金：The authors are grateful for support from the Shanghai Science and Technology Committee (grant no. 14DZ1930802) and the National Natural Science Foundation of China (grant no. 21576080).

语种：英文

外文关键词：Glipizide; Hydroxypropyl methylcellulose acetate; succinate (HPMCAS); Molecular interaction; Molecular dynamics simulation

摘要：Molecular interactions between drug and polymeric carriers are believed to be the key for high drug loading and better physical stability of micro-particles. However, molecular interactions between drug and polymer are still difficult to investigate using only experimental tools. In this study, high-loaded glipizide (GLP)/hydroxypropyl methylcellulose acetate succinate (HPMCAS) (1/1 w/w) micro-particles were prepared using an in situ pH-dependent solubility method. Molecular interactions within the micro-particles were investigated by integrated experimental and modeling techniques. The dissolution rate of GLP/HPMCAS micro-particles was significantly better than those of solid dispersions and physical mixtures. Scanning electron microscopy images showed that the polymer inhibited GLP recrystallization. Experimental (FTIR spectroscopy, differential scanning calorimetry, powder X-ray diffraction and nuclear magnetic resonance spectroscopy) and molecular dynamics simulation revealed that hydrogen-bonding was the key to the properties of the micro-particles. Our research developed high drug-loading GLP/HPMCAS micro-particles and investigated the interactions between drug and polymer at the molecular level. This integrated approach could be practical methodology for future formulation design.