Rheological Characterization of Human Gastric Fluid and development of Viscous Biorelevant Dissolution Media.

In order to obtain a good in vivo-in vitro correlation (IVIVC), biorelevant dissolution media (BDM) are used to simulate the properties of gastric fluid. The viscosities of currently used BDM are close to that of water and are therefore not physiologically relevant. The dissolution rate of a drug compound is influenced strongly by the viscosity of the dissolution medium, and a physiologically relevant viscosity of the medium is therefore important to obtain a good IVIVC. In the present study it was desired to create BDM with viscosities similar to human gastric fluid. Human gastric fluid was collected from 7 volunteers and the rheological behaviour was investigated and the apparent viscosities determined using cone and plate geometry. The apparent viscosity was determined to be 0.0015 - 0.012 Pa∙s measured at a shear rate of ~10 – 1000 sec^-1. The human gastric fluid displayed a predominant elastic behaviour at low oscillation torques (~0.001 – 1 μN∙m). A fasted-state simulated gastric fluid (FaSSGF) was chosen as a starting point for the creation of viscous BDM. FaSSGF was prepared with different amounts of viscosity enhancer added. A natural viscosity enhancer used for the study was negatively charged porcine gastric mucin (PGM). The other viscosity enhancer used was the semi-synthetic neutral polymer hydroxypropyl methylcellulose (HPMC). FaSSGF containing HPMC displayed an elastic behaviour whereas FaSSGF containing mucin displayed a viscous behaviour. It was found that the addition of 0.2 – 0.6 % HPMC or 1 – 5 % mucin produced media with a viscosity range similar to that of human gastric aspirates. HPMC was the preferred viscosity enhancer due to the rheological behaviour, whereas PGM was preferred due to the natural charge.