Hao Shilei, Wang Bochu, Wang Yazhou
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China.
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China.
Eur J Pharm Sci. 2015 Apr 5;70:72-81. doi: 10.1016/j.ejps.2015.01.009. Epub 2015 Jan 30.
Density-dependent gastroretentive drug delivery systems have been used to prolong the gastric retention time of drugs since the 1960s. The design of density-dependent gastroretentive dosage forms, however, usually focuses on specific parameters rather than combines with the fluid dynamics of dosage form in the gastric emptying. Therefore, the purpose of the present study was to develop a 2-D model of multiple-phase flows for the simulation of gastric emptying and gastroretentive microparticles motion, and the influence of microparticle density, microparticle viscosity, and gastric juice viscosity on the gastric retention were studied. The recirculating flows, formed in the gastric emptying, could mix the conventional-density microparticles and transport them to the pylorus. However, the low-density microparticles remained floating on the surface of gastric juice, while the high-density microparticles could sink and deposit in the bottom of the stomach. The remaining integral area of microparticles was higher than 90% after 18.33min of simulation when the density of microparticles was lower than 550kg/m(3) or higher than 2500kg/m(3), which was higher compared to conventional-density microparticles (67.05%). These results are in good agreement with experimental data previously reported. In addition, the viscosity of microparticle and gastric juice also influenced the remaining integral area of gastroretentive microparticles. This study shows that the multiple-phase computational fluid dynamics models could provide detailed insights into the fluid dynamics of density-dependent gastroretentive microparticles in gastric emptying, which offers a powerful tool to further understand the mechanism of gastric retention for gastroretentive dosage forms and study the influence of different parameters on their ability for gastric retention.
自20世纪60年代以来,密度依赖型胃滞留给药系统一直被用于延长药物的胃滞留时间。然而,密度依赖型胃滞留剂型的设计通常侧重于特定参数,而非与剂型在胃排空过程中的流体动力学相结合。因此,本研究的目的是建立一个多相流二维模型,用于模拟胃排空和胃滞留微粒的运动,并研究微粒密度、微粒粘度和胃液粘度对胃滞留的影响。胃排空过程中形成的循环流可以混合常规密度的微粒并将它们输送到幽门。然而,低密度微粒仍漂浮在胃液表面,而高密度微粒会下沉并沉积在胃底部。当微粒密度低于550kg/m³或高于2500kg/m³时,模拟18.33分钟后微粒的剩余积分面积高于90%,这比常规密度微粒(67.05%)更高。这些结果与先前报道的实验数据高度一致。此外,微粒和胃液的粘度也影响胃滞留微粒的剩余积分面积。本研究表明,多相计算流体动力学模型可以深入了解密度依赖型胃滞留微粒在胃排空过程中的流体动力学,为进一步理解胃滞留剂型的胃滞留机制以及研究不同参数对其胃滞留能力的影响提供了一个有力工具。