Open Flow Micro-Perfusion Franz Cell Skin Diffusion
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Solution Overview
Problem
Current methods for characterizing the diffusion of active pharmaceutical ingredients (APIs) through the skin are limited, particularly in evaluating API delivery beyond the stratum corneum and into deeper skin layers, such as the dermis and subcutis.
Innovation Solution
The combination of open flow micro-perfusion (OFM) with the Franz Diffusion Cell (FDC) provides an improved in vitro method for evaluating the diffusion of compounds, such as APIs, into the skin, allowing for the assessment of API passive diffusion beyond the stratum corneum barrier.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If Franz Diffusion Cell (FDC) is used to evaluate API diffusion through skin, then passive diffusion across stratum corneum can be measured, but API biodistribution in deeper dermis and subcutis cannot be detected
Solution Approach 1:
The skin is divided into multiple explants with different thicknesses to segment the measurement depth. Thin skin explants (0.5-2 mm) enable detection in upper dermis using FDC, while thick skin explants (3-6 mm) enable detection in lower dermis and subcutis using OFM, allowing comprehensive coverage of all skin layers
Solution Approach 2:
Open flow micro-perfusion (OFM) technology is introduced as an intermediary method to complement FDC. OFM uses micro-dialysis probes to sample interstitial fluid in deeper tissue layers, acting as a mediator that extends the detection capability beyond what FDC alone can achieve
2Ease of operation
If only Franz Diffusion Cell method is used, then the methodology is simple and widely applicable, but it reveals little about excipient-dependent API biodistribution in deeper dermis
Solution Approach 1:
Two established methods (FDC and OFM) are merged into a unified workflow. FDC provides simple, widely applicable diffusion measurement while OFM adds the capability to measure excipient-dependent biodistribution in deeper layers, combining the advantages of both approaches
3Loss of time
If PBPK modeling is used to predict API bioavailability, then clinical trials can be reduced or eliminated, but the models lack precision for comparing complex pharmaceutical formulations with different excipients
Solution Approach 1:
Comprehensive in vitro characterization of API and excipient effects on diffusion and biodistribution is performed preliminarily using the combined FDC-OFM approach. This preliminary data builds and validates formulation-specific PBPK models, enabling accurate predictions that reduce or eliminate the need for lengthy clinical trials
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This combined method enables the generation of time-resolved permeation profiles across multiple skin layers, providing a more comprehensive understanding of API delivery and biodistribution, which is not achievable with either method alone.
Implementation Method 1
FDC has the limitation that whilst this methodology can provide reliable data related to passive diffusion of an API across the skin barrier
Implementation Method 2
determining the concentration of the compound within the second skin explant using open flow micro-perfusion (OFM)
Data Source
AI summary
The present invention relates to improved methods for characterising diffusion of compounds through the skin using open flow micro-perfusion (OFM) in conjunction with Diffusion Cell apparatus, particularly static Franz Diffusion cell (FDC). The methods are in vitro methods using ex vivo skin explants.