Theoretical comparison of hydrodynamic diffusion layer models used for dissolution simulation in drug discovery and
1Global Research & Development, Research Formulation, Sandwich Laboratories, Pfizer, Inc., Kent, UK. Kiyohiko.Sugano@pfizer.com
International Journal of Pharmaceutics
|August 5, 2008
Summary
A new fluid dynamic (FD) model estimates drug particle diffusion layer thickness for oral absorption. This model accurately predicts effective hydrodynamic diffusion layer thickness (h(eff)) for larger particles, unlike previous approximations.
Area of Science:
- Pharmacokinetics
- Fluid Dynamics
- Drug Delivery
Background:
- Accurate simulation of oral drug absorption requires understanding the effective hydrodynamic diffusion layer thickness (h(eff)) of drug particles.
- Existing approximation models (Hintz and Johnson (HJ), Wang and Flanagan (WF)) have limitations in estimating h(eff).
Purpose of the Study:
- Introduce a novel h(eff) estimation method based on fluid dynamic theory (FD model).
- Compare the FD model's performance against the HJ and WF approximation models.
Main Methods:
- The FD model estimates particle relative velocity using terminal slip velocity and microeddy effects.
- Particle radius (r(p)), drug density, agitation strength, fluid viscosity, and diffusion coefficient are key inputs for the FD model.
Main Results:
- For small particles (r(p)<15 micrometers), all models yielded similar h(eff) values.
- For larger particles (r(p)>15 micrometers), the FD model provided different h(eff) values compared to HJ and WF models.
- The FD model offers a priori theoretical estimation of h(eff).
Conclusions:
- The FD model provides a more comprehensive and sophisticated simulation of oral absorption.
- The FD model's ability to account for varying hydrodynamic conditions in the gastrointestinal tract is a significant advantage.
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