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,certa...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 vip of drug/polymer ICs from homopolymers to block copolymers of poly（ethylene glycol）（PEG） and poly（s-caprolactone）（PCL）.The block length in the vip 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.展开更多
The complexation oflanthanide(Ⅲ) cations with 1,2-propanediaminetetraacetate (1,2-PDTA) in aqueous solution has been investigated by ^(23)Na,^(35)Cl,~2H and ^(17)O NMR shift measurements.It has been shown that the co...The complexation oflanthanide(Ⅲ) cations with 1,2-propanediaminetetraacetate (1,2-PDTA) in aqueous solution has been investigated by ^(23)Na,^(35)Cl,~2H and ^(17)O NMR shift measurements.It has been shown that the contact shifts are dominant for ^(17)O,^(35)Cl and ~2H (only for the heavier lanthanide series) and the pseudocontact shifts are dominant for ^(23)Na.It is suggested that the 1,2-PDTA ligand is bound pentadentately via the two nitrogens and the three carboxylates for the lighter lanthanide complexes,hexdentately via the two nitrogens and the four carboxylates for the heavier ones.The numbers of the water coordinated were determined.The small amount of chloride anion in inner coordination sphere was observed.展开更多
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)
文摘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 vip of drug/polymer ICs from homopolymers to block copolymers of poly（ethylene glycol）（PEG） and poly（s-caprolactone）（PCL）.The block length in the vip 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.
基金Project supported by the National Natural Science Foundation of China
文摘The complexation oflanthanide(Ⅲ) cations with 1,2-propanediaminetetraacetate (1,2-PDTA) in aqueous solution has been investigated by ^(23)Na,^(35)Cl,~2H and ^(17)O NMR shift measurements.It has been shown that the contact shifts are dominant for ^(17)O,^(35)Cl and ~2H (only for the heavier lanthanide series) and the pseudocontact shifts are dominant for ^(23)Na.It is suggested that the 1,2-PDTA ligand is bound pentadentately via the two nitrogens and the three carboxylates for the lighter lanthanide complexes,hexdentately via the two nitrogens and the four carboxylates for the heavier ones.The numbers of the water coordinated were determined.The small amount of chloride anion in inner coordination sphere was observed.
