Understanding the Potential for Dissolution Simulation to Explore the Effects of Medium Viscosity on Particulate...

Area of Science:

• Pharmacokinetics and Drug Delivery
• Computational Fluid Dynamics
• Physical Chemistry

Background:

• Medium viscosity influences dissolution system hydrodynamics.
• Dissolution simulation is a valuable tool for mechanistic studies.
• Understanding simulation limitations is essential for appropriate use.

Purpose of the Study:

• To explore the effects of slightly viscous media on particulate dissolution using simulation.
• To illustrate simulation approaches and their limitations.

Main Methods:

• Utilized the SIMDISSO™ lumped parameter fluid dynamics dissolution simulation model.
• Simulated dissolution of 20 and 200 μm particles in water, milk, and a nutrient drink (viscosities 0.7, 1.4, and 12.3 mPa.s at 37°C).
• Investigated effects of flow rate, modality, viscosity, and particle motion/sedimentation in flow-through and paddle apparatuses; employed Shadowgraph Imaging (SGI) for particle suspension visualization.

Main Results:

• Flow rate, viscosity, and particle motion/gravity significantly affected larger particle dissolution simulations.
• SGI showed particles remained suspended in 1.4 mPa.s medium but sedimented in water.
• Viscosity-adjusted diffusion significantly impacted both particle sizes.

Conclusions:

• Even minor viscosity increases can alter larger particle dissolution.
• Dissolution simulations provide mechanistic insights when assumptions and limitations are clearly understood.
• The 1D simulation approach has greater limitations for larger particles in low-velocity environments.