Research On Abnormal Dynamic Behavior Of Nanoconfined Small Molecule Glass

As an important material in daily life,production and science and technology,glass has many unique physical and chemical properties.The research shows that the glass drug has higher water solubility and higher bioavailability than the crystal drug,and has a very broad application prospect,so it has a very significant research value.However,because the glassy state is in a high-energy metastable state,it will gradually change to a low-energy state when placed in the air,that is,it will gradually relax to the crystalline state,resulting in the loss of the original value of drugs.This phenomenon limits the further application of glassy drugs,which is a great challenge for the pharmaceutical industry,and an effective mean is urgently needed to prevent this behavior and keep it in an effective state.Recently,some researchers have found that glassy materials show various physical properties different from the bulk when their geometric size is reduced,which provides a new idea for improving the stability of glassy materials.Studies have found that some glasses exhibit higher glass transition temperatures(indicating high stability)but lower relaxation activation energy(indicating low stability),which has always been a puzzling problem.In this paper,the abnormal dynamic behavior of nano confined D-Mannitol glass was studied by high precision and high rate differential scanning calorimeter.(1)Compared with the free state critical cooling rate of 200 K/s,the critical cooling rate of D-Mannitol confined in the larger pore is 10 K/s,while the critical cooling rate of D-Mannitol confined in the smallest pore is less than 1 K/s.The glass transition temperature(T_g)of D-Mannitol increases more and more with the decrease of nano pore size,and increases about 41 K in the minimum pore size(heating rate is 1000 K/s).At the same time,the fragility of D-Mannitol decreases with the decrease of nano pore size,which indicates that the glass forming ability and dynamic stability of D-Mannitol are significantly improved after confinement,and the effect of improvement is gradually enhanced with the decrease of nano pore size,the strength of interface effect increases with the decrease of nano pore size.(2)In the isothermal annealing process,the relaxation of D-Mannitol before and after confinement shows a two-step relaxation phenomenon fromβrelaxation toαrelaxation,but the relaxation activation energy E*decreases after confinement,especially in the minimum size confinement.At the same time,it is found that the activation entropy S*is also significantly decreased after nano confinement,resulting in larger activation free energy G*and higher thermal stability.These results indicate that the activation entropy S*may provide a new insight for understanding the abnormal dynamics of nano confinement glass system.(3)The phenomenon of liquid-liquid phase transition in the annealing process of free state D-Mannitol is restrained due to the strong adsorption between the sample and the nanopore wall,and the X phase with stronger hydrogen bond will not be formed.At the same time,because there is no crystallization in the small nano size,the glass phase with ultra-high stability is successfully prepared,which is conducive to the effective protection of D-Mannitol storage and market application.