The ex vivo permeation of ATR from different preparations was determined using previously described diffusion cells [29 (link)]. The skin membranes were mounted in the diffusion cell, where the stratum corneum side faced the donor (drug-loaded system) and the dermal side faced the receptor compartment which contained 100 mL phosphate buffer (pH 7.4) and 0.02% sodium azide at 37 ± 0.5 °C. Then, 0.2 g of each tested formulations were placed separately into membrane holders and fixed to the glass tubes; skin membranes were used to cover the preparations with the stratum corneum side face. The tubes were attached to the dissolution apparatus with Parafilm (Bemis, Oshkosh, WI, USA) to avoid water evaporation, then they were allowed to stir at 100 rpm. At 0.5, 1, 2, 3, 4, 5, and 6 h after starting the experiment, 1 mL aliquots were sampled from the receptor compartment with the fresh buffer replacement. Samples were analyzed spectrophotometrically (Jenway 6305 spectrophotometer, Jenway, Staffordshire, UK) at 241 nm. Samples collected from permeation of drug-free systems were used as a blank [30 ]. Ex vivo permeation parameters including steady state transdermal flux (SSTF), lag time, and enhancement ratio (ER) for percutaneous absorption of ATR across rat skin were estimated for different formulations.
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