Impact of physiologically relevant viscosity on intrinsic dissolution rate of poorly soluble compounds in simulated gastric media

In order to simulate the in vivo dissolution of drugs, biorelevant dissolution media (BDM), simulating the gastric or intestinal juices are often employed. For gastric BDM, pH, surface tension and osmolality is simulated, however, viscosity has, to our knowledge not been taken into account. The dissolution rate of a drug compound is influenced by the viscosity of the dissolution medium. 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 apparent viscosities determined using cone and plate geometry. The apparent viscosity was determined to be 0.0017 0.012 Pa∙s measured at a shear rate of 178 sec -1 . A fasted-state simulated gastric fluid (FaSSGF) was chosen as a starting point for the creation of viscous BDM. FaSSGF was prepared with addition of different amounts of a viscosity enhancer. Semi-synthetic neutral polymer hydroxypropyl methylcellulose (HPMC) was chosen as a natural viscosity enhancer due to the rheological behaviour. It was found that the addition of 0.2 – 0.6 % HPMC resulted in a medium with a viscosity range similar to the viscosity of human gastric aspirates. Dissolution of Griseofulvin and Cinnarizine in FaSSGF containing HPMC was investigated using the μDISS Profiler system. A decrease in intrinsic dissolution rate (IDR) for both drugs was observed as the viscosity of the media was increased. The IDR was lowered up to 70 % within the physiologically relevant viscosity range.