Density-dependent gastroretentive microparticles motion in human gastric emptying studied using computer simulation

Abstract

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/m3 or higher than 2500kg/m3, 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.