Study On 3D Extrusion Printing And Process Simulation Based On Pharmaceutical Polymers

3D extrusion printing can be used to print polymer matrix containing multiple active ingredients into complex three-dimensional structures,to adjust the dosage and release behavior.Therefore,it has a broad application prospect in the field of personalized preparations.However,it is difficult to achieve smooth extrusion and rapid deposition at the same time based on common pharmaceutical polymers.Various problems,such as low resolution,phase separation and easy collapse,are often observed during printing.This study aims to develop a thermo-sensitive paste as printing matrix to improve the extrusion printability.Besides,the extrusion printing process of pastes was thoroughly evaluated.The results can provide experimental basis for developing personalized oral preparations.Novel immediate-release pastes were prepared based on gelatin matrix,and the effects of formulations and process parameters on extrudability and formability were evaluated.With the insoluble drug(ibuprofen)as a representative drug,two-dimensional,three-dimensional,and combined preparations were printed to evaluate the printability and immediate release performance.It was found that when the gelatin concentration was 30% and the microcrystalline cellulose(MCC)concentration was 25%,the extrusion printability was the best.When the printing temperature was 35?,the printing speed was 5 mm/s,and the printing layer height was 0.5 mm,the appearance and the printing accuracy were the best.With the optimized formulation and process parameters,various ibuprofen oral immediate-release preparations were printed.The two-dimensional preparations had fast-dissolving effects;the three-dimensional preparations had high drug loading and taste masking effects;the combined preparations could be used as multi-dose preparations or used in combination therapy of different therapeutics.The preparations had good appearance,and the drug completely released within 10 min.The results showed that the novel immediate-release paste could be used to print personalized immediate-release preparations.Novel sustained-release pastes were prepared based on gelatin matrix,and the effects of formulations,process parameters,and models on extrudability and formability were evaluated.With the soluble drug(diclofenac sodium)as a representative drug,coated tablets were printed to evaluate the printability and sustained release performance.It was found that when the printing layer height was 0.5 mm,the appearance and printing accuracy of the coating layer were the best.When the coating thickness was 1.6 mm,the printability of the coated tablet was good,and had 24 hr sustained-release property.When the hydroxypropyl methylcellulose(HPMC)concentration was 25%,the printing temperature was low and the printed tablet had a good appearance and 24 hr sustainedrelease effect.In addition,different shapes affected the in vitro release behavior of coated tablets,although they all had 24 hr sustained-release effects.The results showed that the novel sustained-release paste could be used to print personalized sustained-release preparations.Temperature-viscosity curves and shear rate-viscosity curves of printing materials were evaluated based on static rheology,and the extrusion behavior of printing materials was studied.Time-elastic modulus and time-viscous modulus curves of printing materials were evaluated based on dynamic rheology,and the deposition process of printing materials was studied.It found that the printing paste had an obvious thermo-sensitive characteristic,which was related to the gelatin matrix.The gelling temperature of immediate-release paste containing 25% MCC was 34.7°C.Although the sustainedrelease paste containing 25% HPMC had no obvious gelling temperature,gelation occurred within a certain temperature range.In addition,the paste had a more obvious shear-sensitive property than the pure gelatin matrix.Adding 25% MCC or 25% HPMC significantly enhanced the shear thinning property of the material(the flow index decreased from 0.469 to 0.229 or 0.371,respectively).Adding 25% MCC or 25% HPMC also improved the deformation resistance of the material(the elastic modulus increased from 12.7 k Pa to 212.3 k Pa or 139.5 k Pa,respectively),and resulting that the paste was extruded and deposited as a solid-like state.The results showed that the thermo-sensitive and shear sensitivity properties benefited the smooth extrusion and rapid deposition of the novel paste,and the paste was kept as a solid-like state during extrusion printing.A 2D cross-section geometry model of the flow field during extrusion printing was established,and a steady simulation of the extrusion process was performed using computational fluid dynamics simulation method with optimized immediate-release paste as the representative material.Based on the simulation results,the effects of extrusion flow field were analyzed.The results showed that the total pressure decreased,whereas the turbulent energy and velocity increased,along the direction of flow field from inlet to outlet.The compression deformation of pathlines was observed when the channel narrowed,while extrusion swelling of pathlines was found when the channel widened.By increasing the viscosity of paste,the maximum total pressure at the inlet greatly increased.By decreasing the nozzle diameter or increasing the inlet speed,the outlet flow rate and the total pressure in the flow field could increased.The results showed that the extrusion flow field simulation could visualize the printing process,and the simulation results could be used to quantitatively predict and optimize printing behavior.