Ibuprofen Sustained Release Preparations Via Hot Melt Extrusionandfused Deposition Modeling Methods And Their And In Vitro Evalution

Firstly,the melt processability of ethylcellulose(EC)was investigated,and the plastized formulation was optimized in this study.Ibuprofen(IBP)sustained release particles were prepared via hot-melt extrusion(HME),while IBP sustained release tablets were prepared via fused deposition modeling(FDM).The influence of formulations and process parameters on their appearance and drug release properties was studied.The sutdy could provide experiment results for further application the HME and FDM techniques in sustained release preparations area.In the first section,Torque value,die swell ratio and mechanical properties were determined to evaluate the melt miscibility of EC and seven plasticizers.It was found that five plasticizers(GTA,DBS,VEA,TEC,DBP)could reduce the torque values of EC polymer during HME process.Four plasticizers(VEA,GTA,DBS,DBP)had little influence on die swell ratio(about 95%).Plasticizer could obviously increase the tensile strength and the percent elongation,which influenced by GTA greatest and by DBS least.The miscibility of plasticizer and EC was further studied via HME process and solubility parameter calculation.It was found that the extrudates were uniform and integrated without two-phase separation problem.The Δ δt was less than 7,suggesting the well compatibility between five plasticizers and EC polymer.In the second section,IBP sustained release particles were prepared by HME method.The effect of plasticizers,release modifiers and geometry on processability and drug release behavior were evaluated.The results showed that an optimal process could be obtained when VEA(20%)was used as a plasticizer.The drug released completely(Q24h>95%)when HPMC(40%)was used as release modifier and the geometry was Φ02.0×2.0.Response surface design was used to optimize the process parameters during HME.Temperature,screw speed and residence time were used as factors,while torque value was used as index.The optimal in vitro drug release profile fitted with the first-order equation best,and the drug release mechanism was diffusion-erosion combined.In the third section,IBP sustained release tablets with internal grid structure were fabricated by FDM method.The effect of formulations,process parameters and models on the appearance and drug dissolution were evaluated.The optimal formulation contained 20%IBP and 40%HPMC.The optimal printing parameters were as follows:printing temperature was 178 ℃,printing speed was 45 mm/s,layer height was 0.2 mm.The optimal model was a cylinder with an infill density of 25%and a shell thickness of 0.8 mm.The resulted in vitro dissolution fitted the first order equation best,and the drug release mechanism was diffusion-erosion combined.