In Vitro–In Vivo Correlation and CFD Modeling of Solution Permeation in a PermeaPad® 96-well plates
Problem Statement Topical ophthalmic formulations must achieve sufficient drug uptake across the corneal barrier. We investigated dexamethasone sodium phosphate (DSP) permeation from Newtonian vehicles in an in vitro PermeaPad® 96-well plate and established an in vitro–in vivo correlation (IVIVC) against rabbit aqueous humor data. COMSOL Multiphysics® Use We employed the CFD Module in COMSOL Multiphysics® v5.6 to simulate mass-transfer within the PermeaPad® plate geometry under no-shaking and continuous-shaking conditions (350, 500, 850 rpm). The Laminar Flow and Transport of Diluted Species interfaces were coupled to capture diffusive and convective transport. Simulations ran on a 3D axisymmetric model imported from CAD geometry; no Application Library models or LiveLink™ products were used, nor was the Application Builder invoked. Experimental Setup Two Newtonian donor vehicles were prepared: • PBS (μ = 1 cP) • TheraTears® (0.25 % NaCMC, μ = 10 cP) Each contained 5 mg/mL DSP at pH 7.4 and 300 mOsm. PermeaPad® wells were used (n=6), under either no shaking or continuous shaking (Eppendorf ThermoMixer C). Aliquots were sampled over 120 min and analyzed by UV–Vis plate reader. Rabbit in vivo data (Rosenblum et al., 1967) provided aqueous-humor concentrations for IVIVC. Results • IVIVC: DSP permeation without shaking (Papp =7.1 ×10⁻⁶ cm/s) correlated linearly (R² = 0.9972) with rabbit in vivo levels (Figure 1). • CFD Simulations: Under no shaking, simulated profiles (Figure 2a) matched experimental valuse (≤ ±0.02 % error). Incorporating induced orbital shaking convective flows (Figure 2b) generated nearly identical permeation curves across 350, 500, and 850 rpm, explaining why experimental shaking rates showed no significant differences (ANOVA, p > 0.05). Conclusions & Implications 1. PermeaPad® no-shake experiments reliably predicts in vivo rabbit absorption of DSP. 2. CFD modeling with the CFD Module captures both diffusion-controlled and convection-enhanced mass transfer, revealing that under our conditions shear has minimal impact once transport is boundary-layer limited. 3. These results support the use of PermeaPad® in formulation screening and highlight the power of COMSOL Multiphysics® for in silico optimization of ocular drug delivery.
