Development and Implementation of a Hinderance-based In Vitro Model for Porous Membranes.

In vitro release testing (IVRT) is an inexpensive and routine step in dermal formulation development where an inert membrane separates the donor formulation from a receptor solution. Experimental IVRT data provides insights into formulation behaviour in the absence of skin permeation complexities. This source of formulation data has the potential to be incorporated into a modelling workflow to aid parameterisation of a mechanistic dermal physiologically based pharmacokinetic (PBPK) model. Therefore, a hinderance-based IVRT model was developed within the Simcyp in vitro permeation testing (IVPT) module framework, using membrane characteristics to inform drug movement through inert, non-silicone, membranes. Modelling as a cylindrical pore system, the membranes key characteristics (pore size, porosity, tortuosity and membrane thickness) are utilised to parameterise a 2-step model where drug enters the membrane pores, diffuses across and partitions into the receptor solution. A description of the model's equations and setup are provided in addition to an ibuprofen in vitro case study using a range of membranes for model performance validation. Comparison of simulated IVRT to experimental data using membranes of microfiltration (pore diameters > 0.1 µm) resulted in acceptable performance, while simulation of nanofiltration membranes (pore diameters < 0.01 µm) require optimisation steps.