2019 PharmSci 360
Dermal microdialysis (dMD) measures the concentration of a topically-administered drug that becomes available in the dermis. However, the concentration profile observed depends on the permeability of the drug across the upper layers of the skin as well as on local disposition within the dermis. Using a retrodialysis/microdialysis approach the disposition of a drug in dermis can be estimated independently of the topical formulation to build a dermis unit impulse response function. Such function can be applied to the deconvolution of dermis concentration profiles resulting from the application of dermatological topical formulations to obtain in-vivo flux. This hypothesis was tested during a study investigating the dermis bioavailability of topical gels and creams of metronidazole (MTZ) in mini-pigs. The ability to characterize the absorption process (in-vivo flux) can aid in the development of quantitative IVIVCs to be used in bioequivalence assessments, formulation development, and PBPK modeling.