Development of ionic liquids and eutectic systems for drug-formulations

Pharmaceutical applications of solid drugs face several problems related to polymorphism as well as low water solubility and membrane permeability. This work focused on the preparation and the study of biocompatible formulations containing choline-based ionic liquids (Ch-ILs) or eutectic systems (ES) and methotrexate (MTX), a poorly soluble synthetic antifolate drug commonly used in chemotherapy. The solubility of prepared formulations was evaluated in water, saline solution, and phosphate buffer saline solution (PBS; pH 7.4) at 37^oC. Moreover, octanol-water partition coefficients were also evaluated.

The results concerning the solubility showed that, in the case of water and saline solutions, the prepared formulations containing ILs have approximately 1000 times better solubility compared to MTX alone. In the case of PBS, an improvement of 25 times was observed. On the other hand, except for the formulation containing citric acid, the solubility of ES’s formulations did not present a noticeable improvement.

The preliminary permeability studies were performed by spectrophotometric determination of octanol-water partition coefficients (K_ow). It is important to note that the most promissory formulation is composed by Ch-IL choline hexanoate showing an improvement for partition of MTX as well as the water solubility.