Study On Dispersion State And Dissolution Behavior Of Indomethacin In Hot Melt Extrusion

Indometacin(INM)is a non-steroidal anti-inflammatory and anti-inflammatory drug.It is a water-insoluble drug and has low oral bioavailability,which greatly limits its clinical application.In this paper,the preparation of indomethacin-Poloxamer 188(INM-F-68)solid dispersion was investigated and the processing temperature was found to be higher than the melting point of the polymer carrier and lower than the melting point of the active ingredient of the drug,and at the same time,it is higher than the melting point of the polymer carrier and the active ingredient of the drug,the diffusion,melting and mixing mechanism of INM in F-68 and the experimental study of the hot melt extrusion process of INM-F-68 system.FLUENT fluid calculation software was used to analyze the diffusion and melting laws of single INM particles in carrier F-68 from the perspective of mass fraction distribution of INM-F-68 system in different rotor configuration,rotation speed ratio,and mixing time.Two indexes,the maximum mixing index and the maximum instantaneous mixing efficiency,were selected.The POLYFLOW software was used to intuitively quantify the influence of rotor configuration and process parameters on the dispersion and distribution of INM in a batch-type dual-rotor mixer.The INM-F-68 solid dispersion was prepared using a batch-type dual-rotor mixer to investigate the influence of different rotor configuration and main process parameters on the diffusion,melting,mixing,crystallization of INM in F-68 and the in vitro dissolution process of INM.Numerical simulations and experimental results show that increasing the number of rotor heads properly helps to disperse and distribute the INM nucleus,and increase the concentration and temperature gradient of INM.INM is more dispersed in amorphous or microcrystalline state on F-68.In the process,the dissolution process of INM is facilitated.With the increase of the rotor speed ratio,the INM particles can be melted and stripped more quickly to form a larger concentration and temperature gradient,thereby accelerating the dispersion and mixing and INM diffusion melting process;The increase of mixing time is beneficial to the diffusion between the INM and F-68 phases.The INM particles undergo more full dispersion,dispersive mixing and diffusion melting,and less precipitation of crystals,which is beneficial to increase the dissolution efficiency of INM.