The aim of this study was to control the dissolution rate and permeability of cilostazol. To enhance the dissolution rate of the active pharmaceutical ingredient (API), hot-melt extrusion (HME) technology was applied to prepare a solid dispersion (SD). To control permeability in the gastrointestinal tract regardless of food intake, the HME process was optimized based on physiologically based pharmacokinetic (PBPK) simulation. The extrudates were produced using a laboratory-scale twin-screw hot-melt extruder with co-rotatory screws and a constant feeding rate. Next, for PBPK simulation, parameter-sensitive analysis (PSA) was conducted to determine the optimization approach direction. As demonstrated by the dissolution test, the solubility of extrudate was enhanced comparing cilostazol alone. Based on the PSA analysis, the surfactant induction was a crucial factor in cilostazol absorption; thus, an extrudate with an even distribution of lipids was produced using hot-melt extrusion technology, for inducing the bile salts in the gastrointestinal tract. In vivo experiments with rats demonstrated that the optimized hot-melt extruded formulation was absorbed more rapidly with lower deviation and regardless of the meal consumed when compared to marketed cilostazol formulations.

中文翻译：

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基于计算模拟的热熔挤压剂型的制备，以提高药物的吸收。

这项研究的目的是控制西洛他唑的溶解速率和渗透性。为了提高活性药物成分（API）的溶解速率，应用了热熔挤出（HME）技术来制备固体分散体（SD）。为了控制胃肠道通透性而不管食物摄入量如何，基于生理学的药代动力学（PBPK）模拟对HME过程进行了优化。挤出物是使用实验室规模的双螺杆热熔挤出机生产的，该挤出机具有同向旋转螺杆和恒定的进料速率。接下来，对于PBPK仿真，进行了参数敏感分析（PSA），以确定优化方法的方向。如溶出试验所证明的，与单独使用西洛他唑相比，挤出物的溶解度得到了提高。根据PSA分析，表面活性剂的诱导是西洛他唑吸收的关键因素。因此，使用热熔挤出技术生产了具有均匀分布的脂质的挤出物，以在胃肠道中诱导胆汁盐。与大鼠进行的体内实验表明，与市售的西洛他唑制剂相比，优化的热熔挤出制剂吸收速度更快，偏差更低，并且不考虑进食量。