Crystalline inclusion complexes formed between the drug diflunisal and block copolymers  

作　　者：Zhi Zhong Xiaotong Yang Xiao-Bin Fu Ye-Feng Yao Bao-Hua Guo Yanbin Huang Jun Xu 

机构地区：[1]Key Laboratory of Advanced Materials(MOE),Department of Chemical Engineering,Tsinghua University [2]Shanghai Key Laboratory of Magnetic Resonance,Institute of Functional Materials,School of Physics and Materials Science,East China Normal University

出　　处：《Chinese Chemical Letters》2017年第6期1268-1275,共8页中国化学快报（英文版）

基　　金：financially supported by the National Natural Science Foundation of China(Nos.21434008,21374054);National Basic Research Program of China(973 Program,No.2014CB932202)

摘　　要：The solid form of drugs plays a central role in optimizing the physicochemical properties of drugs,and new solid forms will provide more options to achieve the desirable pharmaceutical profiles of drugs.Recently,certain drugs have been found to form crystalline inclusion complexes（ICs） with multiple types of linear polymers,representing a new subcategory of pharmaceutical solids.In this study,we used diflunisal（DIF） as the model drug host and extended the guest of drug/polymer ICs from homopolymers to block copolymers of poly（ethylene glycol）（PEG） and poly（s-caprolactone）（PCL）.The block length in the guest copolymers showed a significant influence on the formation,thermal stability and dissolution behavior of the DIF ICs.Though the PEG block could hardly be included alone,it could indeed be included in the DIF ICs when the PCL block was long enough.The increase of the PCL block length produced IC crystals with improved thermal stability.The dissolution profiles of DIF/block copolymer ICs exhibited gradually decreased aqueous solubility and dissolution rate with the increasing PCL block length.These results demonstrate the possibility of using drug/polymer ICs to modulate the desired pharmaceutical profiles of drugs in a predictable and controllable manner.The solid form of drugs plays a central role in optimizing the physicochemical properties of drugs,and new solid forms will provide more options to achieve the desirable pharmaceutical profiles of drugs.Recently,certain drugs have been found to form crystalline inclusion complexes（ICs） with multiple types of linear polymers,representing a new subcategory of pharmaceutical solids.In this study,we used diflunisal（DIF） as the model drug host and extended the guest of drug/polymer ICs from homopolymers to block copolymers of poly（ethylene glycol）（PEG） and poly（s-caprolactone）（PCL）.The block length in the guest copolymers showed a significant influence on the formation,thermal stability and dissolution behavior of the DIF ICs.Though the PEG block could hardly be included alone,it could indeed be included in the DIF ICs when the PCL block was long enough.The increase of the PCL block length produced IC crystals with improved thermal stability.The dissolution profiles of DIF/block copolymer ICs exhibited gradually decreased aqueous solubility and dissolution rate with the increasing PCL block length.These results demonstrate the possibility of using drug/polymer ICs to modulate the desired pharmaceutical profiles of drugs in a predictable and controllable manner.

关 键 词：Pharmaceutical solid forms Inclusion complexes Drugs Block copolymers Thermal stability Aqueous solubility Dissolution profiles 

分 类 号：TQ460.1[化学工程—制药化工]