Based on the solubility of MPTS Cremophor EL was chosen for further studies. It is well known that the amount of excipients present in a composition, especially in an intramuscular parenteral preparation, might have a significant effect on the overall toxicity of the final preparation (Amin and Dannenfelser, 2006 and Medlicott et al., 1998). Therefore, it was the aim of the study to develop a composition with an adequate solubilizing power while utilizing as little amount of excipients as possible. The use of Antidiabetic Compound Library chemical structure ethanol was not excluded based on the fact that the

administration of a highly concentrated solution of MPTS would mean that the total volume of injection is low, therefore the administered dose of ethanol is also very low. Taking the above, and the solubility enhancing effect of co-solvents and surfactants into consideration, it was evident that a more effective

system www.selleckchem.com/products/obeticholic-acid.html was needed to solubilize higher concentrations of the drug. Although the combination of co-solvents with surfactants were shown earlier to have only few advantages, in some cases their combination is desirable, as shown by the marketed compositions of cyclosporine and paclitaxel which were solubilized in Cremophor + ethanol combinations (Kawakami et al., 2004, Kawakami et al., 2006, Kovacs et al., 2009 and Kovacs et al., 2010). Therefore, the excipients that showed the highest solubilizing power during the first two phases of the studies were combined in the hope of developing a solvent system that is capable of solubilizing higher MPTS concentrations than those seen in co-solvent/water and surfactant/water systems. Cremophor EL was chosen as the surfactant (it solubilized the most MPTS out of the surfactant

type excipients), and ethanol and/or PEG200 were chosen as the co-solvents. The above mentioned co-solvents were combined with increasing amounts of Cremophor EL to form the following solvent systems: to surfactant + 75% ethanol, surfactant + 75% PEG 200, surfactant + 37.5% ethanol + 37.5% PEG 200 (=75% ethanol:PEG200 = 1:1). Fig. 4 shows the solubility of MPTS in these solvents. The solubilizing effect of the tested systems can be classified as negative, additive or synergistic based on how much more or less MPTS is solubilized in the surfactant/co-solvent/water combination than in the corresponding co-solvent/water and surfactant/water systems. The measured solubility of MPTS in the combination system of Cremophor EL and PEG200 was lower than the calculated solubility of the antidote candidate if the solubility values measured in Cremophor EL/water and PEG200/water were added (Table 3).