Discovery of Transdermal Penetration Enhancers by High-throughput Screening
Background
Chemical Penetration Enhancers Properties
* Alter stratum corneum structure
* Different formulations including surfactant, fatty acids/esters, terpenes and solvent
* More design flexibility
* Only a small number of CPEs can induce significant enhancement to skin penetration
* Cause irritation to skin
Fig4. Anatomy of the skin. Stratum corneum layer is composed of several fatty acid, cholesterol, sphingolipid and cholesterol esters
CPEs Requirements
* Enhance the permeability to maximize the ability to delivery active ingredient through the skin
* Avoid skin irritation due to high concentration of use of CPEs
Introduction to the Combinatorial Effect of CPEs
* Synergistic combinations of penetration enhancers (SCOPEs) are the enhancer mixtures of two or more CPEs, which exhibit
more efficient and lower irritation.
* Identification of appropriate SCOPE is quite challenging due to the interaction between enhancers and with skin and the
number of CPEs in the library.
* The traditional method used to screen SCOPEs is Franz Diffusion Cells (FDC) (Fig.5), which relies on steady-state measurements
of drug transport across the skin membrane. This is not ideal for high-throughput screening.
* The need to develop a method to screen SCOPEs effectively must emerge to save time and money.
* New discovered SCOPEs must be validated both in-vitro and in-vivo.
Fig5. The Franz Diffusion Cells (FDC) aparatus used to screen SCOPEs