Hot-melt extrusion promotes dissolution,extends“spring-parachute”process and inhibits crystallization in supersaturating microparticle systems

作     者：Yanfei Zhang Huifeng Zhang Huan Yu Yinghui Ma Chengyi Hao Xiaoying Lin Yong Zhang Zhengqiang Li Xianrong Qi Jia Zeng Nianqiu Shi Yanfei Zhang;Huifeng Zhang;Huan Yu;Yinghui Ma;Chengyi Hao;Xiaoying Lin;Yong Zhang;Zhengqiang Li;Xianrong Qi;Jia Zeng;Nianqiu Shi

作者机构：School of Pharmacyjilin Medical University Jilin132013jilin ProvinceChina Collge of Life ScienceJilin UniversityChangchun130012jilin ProvinceChina Department of PharmaceuticsSchool of Pharmaceutical SciencePeking UniversityBeijing100191China College of Pharmaceutical SciencesYanbian UniversityYanji133002jilin ProvinceChina 

出 版 物：《Particuology》 (颗粒学报（英文版）)

年 卷 期：2023年第78卷第7期

页      面：35-48页

核心收录：

学科分类：08[工学] 080502[工学-材料学] 0805[工学-材料科学与工程（可授工学、理学学位）] 

基　　金：supported by National Natural Science Foundation of China(No.82172593 and 82204729) Science and Technology Development Program of Jjilin Province of China(No.20210101430JC,YDZJ202201ZYTS234 and YDZJ202201ZYTS223) China Postdoctoral Science Foundation(No.2015M571373) Science and Technology Development Program of jilin City in Jjilin Province of China(No.20200104067,201831739 and 201464053) Scientific Research Foundation of the Education Department of Jilin Province of China(No.JJKH20191072KJ and 2015-401) Doctoral Research Startup Fund Project of Jilin Medical University(No.JYBS2021002LK) the College Students'Innovation Project of Jilin Province(No.202013706026) 

主　　题：Hot-melt extrusion-triggered amorphization Extensionof"spring-parachute"process Promotion of dissolution/solubility Inhibition of crystallization from a supersaturated state Amorphism-based supersaturating drug microparticle systems 

摘      要：Despite the potential advantages of amorphism-induced supersaturation,the merit of new amorphiza-tion formation methods on the properties of the amorphous drug including the stability of the amor-phous state,dissolution/solubility,supersaturation,andspring-parachuteprocess is still poorly understood,particularly for certain amorphous supersaturating drug delivery systems(aSDDS).The present work aimed to explore the detailed merit of current attractive amorphization manufacturing methods(i.g.,hot-melt extrusion(HME)technique)on the property improvement of aSDDS in form of amorphous solid dispersion microparticles by employing a model Bcs II drug nitrendipine and a polyvinylpyrrolidone-based model polymer *** asDDS systems were developed by various methods,and their physicochemical properties were characterized by SEM,PXRD and ***-triggered amorphization induced superior supersaturation by the observation of the highest dissolution and *** induced the optimal supersaturation duration by the observed greatest extension ofspring-parachuteprocess(e.g,maximum AUCspring-parachute).HME technique is comparable with other techniques for the stabilization of amorphous state during *** aSDDS systems by HME and other methods showed improved long-term stability of the amorphous state in comparison to the pure amorphous *** transformation infrared spectroscopy,Noyes-Whitney equation,nucleation theory and Gibbs free energy of transfer(△G)were used to analyze the underlying ***-lecular mechanism studies indicated that HME caused a stronger crystallization inhibition effect in the asDDS systems than other methods,but molecular interaction is not a dominant mechanism for property enhancement caused by *** the mechanism associated with the polymer itself(PVPVA64),it could inhibit the drug recrystallization,solubilize the drug spontaneously and cause the improved molecular interactions in all aSDDS *** study provided