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From simulation to application: enhancing preclinical evaluation of dissolvable microarray patches through PBPK
Maja Railic1, Wilhelmus E A de Witte2, Stephan Schaller2
1SSPC, Research Ireland Centre for Pharmaceuticals, School of Pharmacy, University College Cork, Cork, T12 K8AF, Ireland. 121100335@umail.ucc.ie.
Drug Delivery and Translational Research
|October 10, 2025
Summary
Physiologically Based Pharmacokinetic (PBPK) modeling enhances drug delivery via dissolvable microarray patches (MAP). This optimized PBPK model accurately predicts drug kinetics, accelerating preclinical development for regulatory approval.
Area of Science:
- Pharmacology and Pharmaceutical Sciences
- Biomedical Engineering
- Computational Biology
Background:
- Dissolvable microarray patches (MAP) offer advanced drug delivery but lack standardized preclinical evaluation protocols, hindering regulatory approval.
- Physiologically Based Pharmacokinetic (PBPK) modeling can predict drug kinetics for MAP, overcoming limitations of traditional in vitro and in vivo studies.
- Adapting PBPK models for MAP is challenging due to complex interactions between microneedle design, drug release, and skin physiology.
Purpose of the Study:
- To optimize an existing dermal PBPK model for predicting drug disposition from dissolvable MAP.
- To incorporate microneedle geometry and in vitro drug release data into the PBPK model.
- To validate the model's predictive accuracy using diverse drug molecules and preclinical data.
Main Methods:
- An existing dermal PBPK model was adapted using MoBi® software.
- Microneedle geometry and in vitro release profiles of loratadine (LOR), chlorpheniramine maleate (CPM), and itraconazole (ITZ) MAP formulations were integrated.
- Model parameters for skin properties and drug diffusion/partitioning were systematically optimized.
- In vitro permeation studies with porcine skin (CPM, LOR) and in vivo preclinical studies in pigs (ITZ) were used for validation.
Main Results:
- The optimized PBPK model successfully predicted drug kinetics for MAP containing LOR, CPM, and ITZ.
- Model refinement enhanced predictive accuracy by systematically adjusting skin-related input parameters.
- Validation against both in vitro and in vivo data confirmed the model's robust performance across different drugs and conditions.
Conclusions:
- The optimized PBPK model provides a powerful tool for predicting drug behavior from dissolvable MAP.
- This modeling approach can significantly accelerate the preclinical development and regulatory assessment of MAP-based therapeutics.
- Standardized PBPK modeling offers a viable strategy to overcome current barriers in MAP translation.
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