Crystal Engineering Strategies for Optimizing Skin Permeation

In the words of the FDA, transdermal and topical delivery systems (TDSs) are methods of systemic and local administration of drugs whose numerous advantages have been somehow overshadowed by their development challenges. Just as it is essential for transdermal drugs to reach the site of action through systemic circulation, topical medications are supposed to bear upon the application zone. Modifying permeability as a fundamental feature in drug delivery seems to be one of the major hurdles standing in the way of TDS advancement. Pharmaceutical crystal engineering has introduced strategies for ameliorating drug skin permeation under more controlled conditions by maintaining the therapeutic efficacy. Yet, permeability measurements of cocrystals/organic salts have been neglected, mainly because the ex vivo models and the in vitro cell culture techniques of assessing drug permeation were more user-dependent, demanding, and fallible compared to recent approved artificial in vitro assays. This work, relying on the crystal engineering point of view, reassesses the correlations between permeability and other investigated parameters, gives insights into the methods of permeability measurements, highlights the implemented innovations, and compiles a comprehensive library accordingly. The unique, critical attitude toward the topic bestows on this Perspective the value of being an instruction for interested readers.