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In Vitro
Journal Article
Skin uptake and clearance of ciclopirox following topical application.
Biopharmaceutics & Drug Disposition 2013 December
The assessment of skin uptake and clearance are important to determine the efficiency and systemic safety of dermatological formulations. The objective of this study was to assess the skin uptake, clearance and possible systemic delivery of ciclopirox following topical application in Wistar rats. In vitro studies (3 h) were carried out in excised pig skin to assess the permeation and retention capacity of ciclopirox in skin layers using gel formulations (1% and 2% w/v). In vivo dermatopharmacokinetics (DPK) parameters were determined by measuring the drug levels in the skin as a function of time post application (0.5, 1, 1.5 and 2 h) and post removal (3, 4, 6 and 8 h) of the formulation in Wistar rats. The plasma drug concentrations were also determined in the same animals. In vitro data indicate the low permeability and high retention of ciclopirox in the stratum corneum. The DPK data observed indicate a higher Cmax value (175.43 ± 25.62 μg/cm2) and AUC (632.14 ± 102.26 μg.h/cm2) with the 2% (w/v) gel formulation. Further, the skin elimination of ciclopirox follows first order kinetics with a short half-life (t1/2 ~2 h). The fraction of drug reaching the systemic circulation was found to be significantly low (~0.15% of the applied dose). A relation between the drug concentration in the skin layers and the plasma was observed with a short lag period. The topical availability of ciclopirox was found to be relatively low and endured rapid clearance with minimal systemic uptake.
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