Fig. 2 shows the solubility of MPTS in the co-solvents. The inserted figure shows the solubilized drug concentrations up to a higher value, PFI-2 concentration while the

large figure shows the values up to a lower concentration so as to facilitate the distinction between the solubilizing effects of the PEGs. The solubility enhancing effect attributed to the co-solvents can be explained (a) by their ability to interrupt the hydrogen bonding structure of the water molecules, thus decreasing the squeezing out effect of non-polar molecules from the polar solvent; and (b) by their ability to decrease the dielectric constant of the solvent system. The exponential solubility curve seen in the case of MPTS (Fig. 2) correlates well with the previously published solubility tests using co-solvents (Higuchi et al., 1953). These studies, ON-01910 order known as the log-linear model, reported that a linear increase in the concentration of the co-solvent increases the solubility of drugs exponentially, (Yalkowsky et al., 1972 and Yalkowsky et al., 1976). Results show that the most effective solubilizer is ethanol, solubilizing 177.11 ± 12.17 mg/ml MPTS at 90% and 44.35 ± 5.15 mg/ml MPTS at 75%. PEG200, PEG300 and PEG400 exerted similar solubility enhancing capacities, but their solubilizing power falls short of the one encountered with ethanol. Based on the solubility enhancing effect of the co-solvents, ethanol and PEG200 were picked to be included in further studies when co-solvents were combined

with surfactants. In step two of the studies, the effect of surfactant/water systems on the solubility of MPTS was examined using Cremophor EL, Cremophor RH40, polysorbate 80, sodium cholate and sodium deoxycholate at 1%, 5%, 10%, 15% and 20%. Fig. 3 shows the solubility of MPTS in the various

surfactant compositions. The solubilizing effect of surfactants rests on their ability to orient to the interface between a molecule and water and their ability to form micelles above the critical micellar concentration in aqueous solutions (McBain, 1913). All surfactants used in this experiment were above this concentration (cmc values: Cremophor EL = 0.002%, Cremophor RH40 = 0.039%, polysorbate 80 = 0.016%, sodium cholate = 0.388–0.603%, sodium deoxycholate = 0.083–0.249%), thus the solubilizing effect heptaminol can be associated with the number and size of micelles formed (Coello et al., 1996, McBain, 1913, Rowe et al., 2009, Tellingen van et al., 1999 and Wan and Lee, 2006). Fig. 3 shows that the solubility of MPTS increased linearly with the linear increase in the concentration of the surfactants. Out of the tested surfactants, the highest solubility of MPTS was achieved in Cremophor EL at all tested concentrations, with maximum MPTS solubility of 40.99 ± 1.55 mg/ml at 20% Cremophor EL concentration. All the other surfactants increased the solubility of the molecule at different rates, in the following order: Cremophor EL > Cremophor RH40 > polysorbate 80 > sodium deoxycholate > sodium cholate.