| Because of their special physical and chemical properties,glassy materials have promising application prospects in many fields,especially in the field of biomedicine.Compared with crystalline drugs,glass drugs have faster dissolution rate and higher solubility.However,the metastable glass will relax to lower energy and even crystallize in the natural state,which will lead to the change of the performance,even failure,making the pharmaceutical filed facing a huge challenge.Therefore,the study of ultrastability glass has special value and basic research value.In recent years,many research results show that the size effect and interface effect caused by nano-confinement have a significant impact on the structure and performance of glass,which brings hope for us to control the structure and performance of glassy materials.However,how these two effects work in the limited system is still controversial in academia.Based on this situation,we chose D-mannitol(DM)which is widely used and easy to crystallize as samples,and studied the influence of different interface and nano scale substrate constraints on the performance of DM.In this work,we prepared the confined DM by the melt infiltration method,and studied the relaxation kinetics of the confined DM in different nanopore AAO templates by high-precision flash differential scanning calorimeter.We found that when the pore size was less than 50 nm,the crystallization behavior was depression.The brittleness of the confined glass is obviously reduced,which means that the confined glass liquid is stronger than the free system,and the glass forming ability is enhanced.It is intriguing that during isothermal annealing both confined and free DM glasses relaxation kinetics experience two relaxation stages(β-to-α)that have distinct activation energies.The relaxation activation energy of the confined glass is about 25%-29% smaller than the free glass,which is attributed to the reduced dimensionality.These abnormal thermodynamic and dynamic properties in AAO confined system is mainly caused by size effect,but the interface between the inner wall of AAO pore and DM is not obvious.In order to explore the effect of interface effect on DM,based on the previous work,we chose copper with a pore size of 20 nm as the substrate.Then,the kinetic and thermodynamic properties of DM confined in copper nanoporous were studied in-situ by high precision flash differential scanning calorimetry.It is confirmed that when DM is confined in nanoporous copper,it shows a new ultrastable glass state.Interestingly,the crystallization behavior of free DM was suppressed and the critical cooling rate changed significantly.The first-order liquid-to-liquid phase transition of free DM during annealing was suppressed and the X phase disappeared.In addition,T_g increased by 12-20 K,and the activation energy of relaxation increased from 107 kJ/mol to 302 kJ/mol,which indicated that the thermal stability of DM was greatly improved after confinement.At last,we confirm that the abnormal ultrastable thermal stability for the confined DM is attributed to the depression of hydrogen bonds and the large adsorption energy of DM on copper,which are verified by the FTIR experiments and density functional theory calculations.These results suggest that interfacial effect has a significant effect on the properties of DM.The abnormal kinetic and thermodynamic behaviors observed in confined DM glass open a new avenue for preparing stable glasses drugs which are difficult to crystallize,and also promoted the development of drug carriers and drug sustained-release fields.Therefore,nano confinement may be a universal novel method for achieving ultrastability in glasses. |
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