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<p><i>In vitro</i> 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<i> in vitro</i> 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 <i>in vitro</i> case study using a range of membranes for model performance validation. Comparison of simulated IVRT to experimental data using membranes of microfiltration (pore diameters &gt; 0.1 µm) resulted in acceptable performance, while simulation of nanofiltration membranes (pore diameters &lt; 0.01 µm) require optimisation steps.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 发表日期：

    2026年5月27日

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  • Daniel A. Paterson,
  • Lucy Coleman,
  • Yuri Dancik,
  • Kanika Thakur,
  • Yanling Zhang,
  • Alice Maciel Tabosa,
  • Sebastian Polak,
  • James F. Clarke

摘要

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.

Graphical Abstract