Dynamics of Dissolution and Diffusion-Controlled Drug Release Systems

Abstract

Analytical expressions were derived to explain the influence of the dissolution/diffusion number (Di) on the time constant and steady-state flux when dispersed drugs are released from a finite matrix. A key novelty of this work is the introduction of a single time-constant that combined the analysis of both dissolution- and diffusion-based systems. Focus is placed on systems with a constant dissolution rate and diffusion coefficient. Solutions, based on the residue theorem, were in agreement with published results describing the transport of estradiol in a polymeric matrix. The experimental cumulative amount of drug released was 0.1 mg/cm² in 100 hours compared to 0.084 mg/cm² predicted by the theoretical model. The process time constant, estimated from the first eigenvalue (t0) and a more accurate statistical approach (t(eff)), showed a consistent decrease with increasing Di values. For a dissolution/diffusion number of 0.21, t0 and t(eff) were estimated at 58.44 and 73.02 hrs, respectively. With the presence of a skin layer, t(eff) increased to 575.7 hrs. These results can be used to assess the relative impact of dissolution and diffusion on the time it takes drugs to attain a therapeutic level in the bloodstream.