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

Area of Science:

• Pharmacokinetics
• Formulation Science
• Computational Modeling

Background:

• In vitro release testing (IVRT) is crucial for dermal formulation development, providing data without skin complexities.
• Physiologically based pharmacokinetic (PBPK) models require accurate parameterization for predicting drug behavior.
• Existing IVRT data can enhance PBPK model parameterization.

Purpose of the Study:

• To develop a hindrance-based in vitro release testing (IVRT) model.
• To integrate membrane characteristics into a mechanistic dermal PBPK model parameterization workflow.
• To validate the model's performance using experimental ibuprofen data.

Main Methods:

• Developed a hindrance-based IVRT model within the Simcyp in vitro permeation testing (IVPT) module.
• Modeled membranes as cylindrical pore systems, utilizing pore size, porosity, tortuosity, and thickness.
• Applied a 2-step model describing drug entry, diffusion, and partitioning.

Main Results:

• The model demonstrated acceptable performance for microfiltration membranes (pore diameters > 0.1 µm).
• Simulations for nanofiltration membranes (pore diameters < 0.01 µm) indicated a need for further optimization.
• Model validation was performed using ibuprofen IVRT data across various membranes.

Conclusions:

• The developed IVRT model effectively utilizes membrane characteristics to simulate drug release.
• The model shows potential for parameterizing dermal PBPK models, particularly with microfiltration membranes.
• Further refinement is necessary for accurate simulation of drug release through nanofiltration membranes.