Theoretical comparison of hydrodynamic diffusion layer models used for dissolution simulation in drug discovery and development.
The effective hydrodynamic diffusion layer thickness (h(eff)) of a drug particle dissolving into an agitated fluid is of great importance for oral absorption simulation. The purpose of the present study was to: (1) introduce a h(eff) estimation method based on the fluid dynamic theory (FD model), and (2) compare the FD model with the non-FD-based approximation models previously reported by Hintz and Johnson (HJ model) and Wang and Flanagan (WF model). In the FD model, the relative velocity of a particle suspended in an agitated fluid was estimated from the terminal slip velocity and the microeddy effect. For small particles (particle radius (r(p))<ca. 15microm), the HJ, WF and FD models resulted in the similar h(eff) values, whereas they resulted in different h(eff) values for large particles (r(p)>ca. 15microm). One of the merits of the FD model is that it provides the a priori theoretical estimation of h(eff) from particle radius, drug density, agitation strength, fluid viscosity, and diffusion coefficient. The hydrodynamic conditions in the gastrointestinal (GI) tract differ among human and animals, the GI sites, and fasted/fed conditions, etc. Therefore, the FD model could provide a more comprehensive and sophisticated simulation of oral absorption.
Sugano
Kiyohiko
K
Global Research & Development, Research Formulation, Sandwich Laboratories, Pfizer, Inc., Kent, UK. Kiyohiko.Sugano@pfizer.com
D000284:Administration, Oral; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003198:Computer Simulation; D004058:Diffusion; D007700:Kinetics; D008956:Models, Chemical; D009038:Motion; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D014783:Viscosity
D004364:Pharmaceutical Preparations