Understanding the Potential for Dissolution Simulation to Explore the Effects of Medium Viscosity on Particulate Dissolution.AAPS PharmSciTech. 2019 Jan 07; 20(2):47.AP
Viscosity, influenced by medium composition, will affect the hydrodynamics of a dissolution system. Dissolution simulation methods are valuable tools to explore mechanistic dissolution effects, with an understanding of limitations of any simulation method essential to its appropriate use. The aims of this paper were a) to explore, using dissolution simulation, the effects of slightly viscous media on particulate dissolution and b) to illustrate approaches to, and limitations of, the dissolution simulations. A lumped parameter fluid dynamics dissolution simulation model (SIMDISSO™) was used to simulate particulate (20 and 200 μm diameter) dissolution in media with viscosity at 37 °C of water (0.7 mPa.s), milk (1.4 mPa.s) and a nutrient drink (12.3 mPa.s). Effects of flow rate, modality (constant vs pulsing), viscosity and gravitational and particle motion/sedimentation effects on simulated dissolution were explored, in the flow through and paddle apparatuses as appropriate. Shadowgraph imaging (SGI) was used to visualise particle suspension behaviour. Flow rate, hydrodynamic viscous effects and disabling particle motion and gravitational effects affected simulated dissolution of larger particles. SGI imaging revealed retention of particles in suspension in 1.4 mPa.s medium, which sedimented in water. The effect of diffusion adjusted for viscosity was significant for both particle sizes. The limitations of this 1D simulation approach would be greater for larger particles in low velocity regions of the paddle apparatus. Even slightly viscous media can affect dissolution of larger particles with dissolution simulation affording insight into the mechanisms involved, provided the assumptions and limitations of the simulation approach are clarified and understood.