The Study Of Indomethacin Sustained Release Extrudates Prepared By Hot Melt Extrusion

Hot melt extrusion（HME）has many advantages such as solvent free,low cost,continuous process and potential of automation.Indomethacin（IND）is a BCSII hydrophobic drug with Tm（160℃）for crystals,Tg（45℃）for amorphous states and decomposition temperature of 230 to 320°C.Xylitol is a small molecule with Tm（92°C）for crystals,Tg（-24°C）for amorphous states.HPC_EF is a semi-crystalline polymer with Tm（189°C）for crystals,Tg（-25°C）for amorphous states and carbonize at 260²75°C,it is extrudable at 160°C.HPC_G/M/HF has a phenomenon of die swell.HPMC_K100M is a semi-crystalline polymer with Tg（186°C）for amorphous states.The compatibility between IND(23.9MPa^1/2),HPC_EF(22.4 MPa^1/2)and HPMC_K100M(28.7 MPa^1/2)are good.The purpose of this study is to eliminate die swell,make HPMC_K100M100M extrudable and achieve 24 h zero-order release formulations.In the first chapter,the effects of xylitol ratio on the plasticization and drug release of HPC_G/M/HF were investigated.Rheology results suggested that xylitol can plastify HPC_G/M/HF.Xylitol made the extrudates more flexible.In the second chapter,we investigated the effect of HPC_EF on plasticization and release of HPC_G/M/HF.The results of the melt rheology and the elastic modulus of extrudates showed that the plasticizing effect of HPC_EF on HPC_G/M/HF is not obvious,but HPC_EF can effectively solve the die swell.The plasticizing effect of xylitol was better than HPC_EF.The molecular weight and steric hindrance of xylitol is smaller,which is easier to insert into polymer chains.It destroyed the tangles of HPC polymer chain and increased deformation.Both of xylitol and HPC_EF can play as porogens to adjust the release.In the third chapter,we investigated the effect of HPC_EF on plasticization and release of HPMC_K100M.The results of rheology and the elastic modulus of extrudates showed that HPC_EF has a plasticizing effect on HPMC_K100M.IND has a plasticizing effect on HPMC_K100M-HPC_EF（50:50）,and 30%is the maximum plasticizing ratio.The asymmetric membrane structure of extrudates made them sustained release for 24 h.