Studies On Solid Dispersion Of Epalrestat

The purpose of the study is to prepare epalrestat solid dispersion by hot melt extrusion technique,in order to improve thebioavailability and reduce the adverse reaction.HPLC was used for analysis of epalrestat solid dispersion.Optimal formula was developed by screening critical factors of carrier type,the drug proportion and preparation method.The equilibrium solubility,X-RD,FT-IR and DSC of epalrestat solid dispersion were investigated.Furthermore,the pharmacokinetics parameters of epalrestat solid dispersion was studied in rat model.The linear equation of epalrestat curve was A=34.30C-14.77(R2=0.9999),the precision of intra-and inter-day was separately between 0.16-0.41 and 0.57-1.02,the recoverywas 95.77-104.7%.Poloxamer 188 was screened as carrier with the optimal ratio of Poloxamer:epalrestat=1:3.The final solid powder product with light yellow color was homogeneous dispersion without any agglomerate.The epalrestat solid dispersion was successfully manufactured with qualified parameters of equilibrium solubility,X-RD,FT-IR and DSC.By comparison with the original drug product,the epalrestat solid dispersion showed comparable pharmacokinetics parameters with the original drug product.The developed HPLC method showed high accuracy,low detection limit and quantification limit.The epalrestat solid dispersion was successfully prepared by hot melt extrusion technique,and showed improved solubility in vitro and comparable bioavailability in vivo.