This means that any variations in the Mz flux across skin membranes due to differences in the release pattern from the various formulations can be ruled out, which enable a quantitative comparison between Mz fluxes across skin membranes from the different formulations. Ku-0059436 clinical trial To be able to relate the data on steady state flux of Mz to the water activity in the formulations, we determined the water activity in all formulations studied. This was done using a calorimetric method previously developed in house,

which allows for precision measurements at high water activities (Björklund and Wadsö, 2011). The results are compiled in Table 1. It is noted that the water activity in the formulations containing glycerol or urea in PBS solution is consistent with previous reported values

on glycerol or urea in pure water, taking into account the small drop in water activity due to the PBS buffer salts (Scatchard et al., 1938). The average steady state flux of Mz across skin membranes as function of water activity in the donor formulation (aw,d) is shown in Fig. 1. For comparison, Epacadostat ic50 previous flux data of Mz from formulation containing PEG in PBS solution are also included ( Björklund et al., 2010). It is clear that the subsequent addition of glycerol, urea or polymer to the donor formulations leads to a reduced water activity ( Table 1). Still, the addition of these compounds does not affect the permeability of the skin membrane in the same way ( Fig. 1A and B). It is a striking observation that the flux of Mz remains high for all formulations that contain either glycerol or urea in PBS solution, irrespectively of the water activity ( Fig. 1A). This is in clear contrast to the case when the water activity is regulated by the addition of the PEG polymer (ref. data in Fig. 1A), which does not partition into the skin membrane. In the latter case, there is a 6-fold decrease in Mz flux when the water activity goes below approx. 0.96. The data in Fig. 1A show that for some of the glycerol or urea formulations

the average flux is increased compared ADP ribosylation factor to the neat PBS formulation, of which the latter corresponds to the data point at aw,d = 0.992. However, the variations is not statistically significant (treated by one-way ANOVA, p-level 0.18). In the second set of experiments (Fig. 1B), the water activity in the formulations containing glycerol or urea is regulated by the addition of PEG in the same way as described for the reference samples with no humectant (Björklund et al., 2010). Again, the addition of PEG to the formulations leads to a sharp decrease in flux of Mz at reduced water activities. However, from the comparisons in Fig. 1B, it is clear that the onset of the sharp decrease in permeability is shifted towards lower water activities when glycerol or urea is present in formulations, as compared to the case when they are not.