Assessment of finite and infinite dose in vitro experiments in transdermal drug delivery

Abstract

Penetration, usually with finite dosing, provides data about the total active amount in the skin and permeation, being the most used methodology, usually with infinite dosing, leads to data about pharmacokinetic parameters. The main objective of this work is to assess if results from permeation, most of them at finite dose, may be equivalent to those from penetration usually at infinite dose. The transdermal behavior of four drugs with different physicochemical properties (di-clofenac sodium, ibuprofen, lidocaine, and caffeine) was studied using penetration/finite and kinetic permeation/infinite dose systems using vertical Franz diffusion cells to determine the relationships between permeation and penetration profiles. Good correlation of these two in vitro assays is difficult to find; the influence of their dosage and the proportion of different ionized/unionized compounds due to the pH of the skin layers was demonstrated. Finite and infinite dose regimens have different applications in transdermal delivery. Each approach presents its own advantages and challenges. Pharmaceutical industries are not always clear about the method and the dose to use to determine transdermal drug delivery. Being aware that this study presents results for four actives with different physicochemical properties, it can be concluded that the permeation/infinite results could not be always extrapolated to those of penetration/finite. Differences in hydrophilicity and ionization of drugs can significantly influence the lack of equivalence between the two methodologies. Further investigations in this field are still needed to study the correlation of the two methodologies and the main properties of the drugs that should be taken into account.