Tissue Permeation and Penetration Studies
In vitro measurement of drug permeation across and into a membrane requires the use of a diffusion cell designed to mimic the physiological and anatomical conditions of the membrane in situ: the Franz diffusion cell.
These studies are a very important step in the topical or transdermal formulation development process and correlate well with in vivo studies. MedPharm can test formulations with this system using various ex vivo tissues to establish how much of API crosses the tissue. This can allow:
- Selection of lead candidate APIs/formulations
- Selection of posology
- Optimisation and comparison of formulations
- A level of prediction of the in vivo effect of the formulation
These studies are performed in accordance to guidelines by OECD 428, European Commission (Guidance document on dermal absorption, rev 7, 2004), European Food Safety Authority (Guidance on Dermal Absorption, 2012), and the European Medicines Agency (EMA) EME/CHMP/QWP/911254/2011. Data generated by MedPharm have been accepted by regulatory authorities throughout the world.
Permeation Studies: TurChub® Zone of Inhibition Testing
MedPharm’s Proprietary TurChub® model consists of a bacterial/fungal culture and an excised tissue suspended above the culture. It provides an additional test for certain antimicrobial formulations by combining a permeation study with an indication of efficacy.
When a formulation is applied to the surface on the tissue, permeation and efficacy of an antibacterial/antifungal formulation can be established by measuring the zone of inhibition on the culture plate. The model forms part of the battery for screening formulations. It performs preliminary data for optimisation and lead candidate selection and means that an analytical method for systems such as HPLC or LC-MS/MS is not required.
MedPharm carries out quantification of residual API on the surface of tissue and within the layers of a tissue (for example the Stratum Corneum, epidermis etc of skin). This technique involves removal of the outer tissue layers by tape stripping and processing of the tissue. The API is then recovered using solvent extraction and for assay using the arsenal of analytical systems available to MedPharm’s clients. In addition, full mass balance studies can be performed using fully validated methods and systems.
MedPharm offers these services in a bespoke fashion, tailoring each test to suit the client’s project. It has access to ex vivo human and animal tissue, and can carry out all work in compliance with GLP guidelines.