延胡索乙素固体脂质纳米粒缓释片制备及工艺优化

Hydrogel matrix sustained-release tablets of tetrahydropalmatine -solid lipid nanoparticles: Preparation and prescription optimization

目的:制备延胡索乙素固体脂质纳米粒缓释片,并研究延胡索乙素固体脂质纳米粒缓释片的释药模型和释药机理。方法:乳化-溶剂挥发法制备延胡索乙素固体脂质纳米粒,以乳糖作为冻干剂,羟丙基甲基纤维素(HPMC)为缓释材料进一步制备缓释片。在单因素考察的基础上,设计正交试验优化延胡索乙素固体脂质纳米粒缓释片处方,并对缓释片体外释药模型和释药机理进行探讨。结果:延胡索乙素固体脂质纳米粒缓释片最佳处方为缓释材料HPMC K4M和HPMC K15M比例为1∶1,用量为40 mg,PEG 4000的用量为20 mg,硬脂酸镁用量为片芯质量的0.5%。延胡索乙素固体脂质纳米粒缓释片最佳处方的体外释放行为符合Higuchi释药模型,释药方程为:Mt/M∞=0.286 8 t^1/2-0.073 8(r=0.990 8),12 h内累积释放度为93.56%,缓释片释药机理为扩散和溶蚀共存。结论:制备的延胡索乙素固体脂质纳米粒缓释片,工艺重复性较好,其释药行为符合Higuchi释药模型。

OBJECTIVE To prepare tetrahydropalmatine solid lipid nanoparticle sustained-release tablets and study the release model and mechanism of tetrahydropalmatine solid lipid nanoparticle sustained-release tablets.METHODS Solid lipid nanoparticles of tetrahydropalmatine were prepared by emulsification-solvent evaporation method. Lactose was used as lyophilizer and hydroxypropyl methylcellulose(HPMC) was used as sustained-release material to prepare sustained-release tablets.On the basis of single factor investigation, orthogonal test was designed to optimize the formulation of tetrahydropalmatine solid lipid nanoparticles sustained-release tablets, and the in vitro release model and drug release mechanism of sustained-release tablets were discussed. RESULTS The optimum formula of Yanhusuo B solid lipid nanoparticle sustained-release tablets was that the ratio of HPMC K4 M to HPMC K15 M was 1∶1, the dosage was 40 mg, the dosage of PEG 4000 was 20 mg, and the dosage of magnesium stearate was 0.5% of the tablet core.The in vitro release behavior of the optimal formulation of Yanhusuo B solid lipid nanoparticle extended-release tablets conformed to the Higuchi release model, and the release equation was Mt/M∞=0.286 8t1/2-0.073 8(r=0.990 8). Accumulative release of the prepared hydrogel matrix sustained-release tablets was 93.56% within 12 h. The drug release from the hydrogel matrix sustained-release tablets was controlled by diffusion and degradation of the matrix. CONCLUSION The reproducibility of optimized formulations of tetrahydropalmatine solid lipid nanoparticles sustained-release tablets was favorable, and the drug release behavior conforms to the character of Higuchi model.