Molecular modeling identifies effective topical excipients missed by in vitro experiments
Developing a topical formulation for drug delivery is a challenging task due to the robust nature of the human skin barrier. Often specific permeation enhancers are used in order to increase the permeability of the API of interest. Due to the complex environment present in the skin multiple permeation enhancers are commonly needed, and finding the correct combination is paramount in order to design an effective topical pharmaceutical formulation.
Using ERCO Pharma’s proprietary skin model it is possible to obtain a permeability profile across the human skin barrier in silico. The permeability profile enables the identification of the largest energy barriers in the human skin barrier, that the molecule of interest encounters during its permeation process. Since these properties are unattainable from a conventional in vitro experiment ERCO Pharma’s technology greatly increases the understanding of the challenges that need to be overcome in order to produce an effective topical formulation.
In a conventional in vitro development process, aimed at identifying potential permeation enhancers one at a time, the modified permeation rate of the API across a skin patch will only identify the excipients which are able to modify the major rate limiting barrier.
For APIs which experience multiple permeation barriers across stratum corneum ERCO Pharma’s molecular dynamics simulation approach will also identify those excipients which affect other rate limiting barriers.
This makes it possible for ERCO Pharma to identify potential formulation candidates that would be discarded based on their in vitro ranking, but when combined with a top-ranked excipient might create the most effective topical formulation.