The Particle Drifting Effect: A Combined Function\nof Colloidal and Drug Properties

The particle drifting effect, where\nnanosized colloidal drug particles\novercome the diffusional resistance of the aqueous boundary layer\nadjacent to the intestinal wall and increase drug absorption rates,\nis drawing increasing attention in pharmaceutical research. However,\nmechanistic understanding and accurate prediction of the particle\ndrifting effect remain lacking. In this study, we systematically evaluated\nthe extent of the particle drifting effect affected by drug and colloidal\nproperties, including the size, number, and type of the moving species\nusing biphasic diffusion experiments combined with computational fluid\ndynamics simulations and mass transport analyses. The results showed\nthat the particle drifting effect is a sequential reaction of particle\ndissolution/dissociation in the diffusional boundary layer, followed\nby absorption of the free drug. Therefore, factors affecting the rate-limiting\nstep, which can be either process or both under different circumstances,\nalter the particle drifting effect. Experimental results also agree\nwith the theory that the particle dissolution rate is dependent on\nparticle size, concentration, and drug solubility. In addition, rapid\nbile micelle dissociation and bile salt absorption facilitated drug\nabsorption by the particle drifting effect. Our findings explain the\nhighly dynamic nature of the particle drifting effect and will contribute\nto rational formulation development and better bioavailability prediction\nfor formulations containing colloidal particles.