固体脂质微颗粒载药体系结构与性能关系的探索和介观模拟研究-化学工程专业论文.docxVIP

AbsttactAbstract Absttact Abstract With proper drug delivery system(DDS)，drug release may be sustained and controlled at certain time to target sites，which improves drug efficiency and reduces its side effect．Solid lipid microparticles(SLM)are micro-size DDS made from lipids with hi曲melting point as matrixes．They are characteristic of good biocompatibility and controlling drug release effectively．SLM are complex multi-phase system．Their composition and preparation parameters impose effect on their properties by means of changing their microstructures．In this work，the relationship between SLM microstructures and their properties is investigated， and the influences of composition and preparation parameters on their mierostructures are analyzed．In this way,SLM properties call be optimized by adjusting their microstruetures． During the process，experimental characterization,theoretical analysis，and mesoscale simulation are integratively used to study SLM mierostructures ofdifferent levels． A nonsteroidal anti—inflammatory drug，ibuprofen,is chosen as the model drug． Ibuprofen—loaded SLM are produced with hi曲shear homogenization technique．The effects of preparation parameters on SLM mean diameter,volume distribution，drug entrapment efficiency,as well as SLM mierostructures are investigated,and the preparation parameters are optimized．The entrapment efficiency of ibuprofen in SLM is different with different carrier materials．The reasons lie in two aspects，the compatibility between drug and carrier materials，along with the crystal modification of SLM．The stability of SLM with different stabilizers is investigated and the stabilization mechanism is also analyzed．The optimized formulations of ibuprofen-loaded SLM are obtained by further investigating the effect of stabilizer content and initial drug content on the characteristic of SLM．The release performance of ibuprofen-loaded SLM is investigated in simulated gastrointestinal medium without enzymes．The influences of carrier