There is an emergent need to develop innovative, more effective and specialized release dosage forms, particularly to overcome the poor solubility and permeability of certain classes of drugs. Thus, scientists are actively seeking for more efficient and patient-compliant drug delivery devices. The main drawbacks in the current strategies are the poor drug solubility and bioavailability. Recently, some works reported the potential use of deep eutectic solvents (DES) to overcome these drawbacks. DES can be defined as a mixture of two or more compounds, which has a lower melting point than its pure components due to the strong hydrogen bonding between them. Thus, when combined at a specified stoichiometric ratio the mixture becomes liquid at room temperature. DES were introduced in many applications being recently reported their potential use as template-delivery agents in a controlled manner, and so called therapeutic deep eutectic systems (THEDES).
Herein, we explore the preparation of a new THEDES based on choline chloride-ascorbic acid. We further investigated the possibility to dissolve dexamethasone in this system and proposed it as a new class of pharmaceutical active ingredient (API), with enhanced properties. The system was analyzed by polarized optical microscopy and the thermal behavior and stability of the THEDES was measured by differential scanning calorimetry. The solubility profile of both ascorbic acid and dexamethasone was performed in phosphate buffer solution (pH 7.4) and compared with those of the pure API. Furthermore, the in vitro permeability was evaluated in Franz diffusion cells, using THEDES and the API in powder form. As expected, the solubility and permeability of the dexamethasone was greatly improved when in the THEDES system. In addition, controlled drug delivery systems were developed by supercritical fluid sintering, doping a blend of starch:poly-ɛ-caprolactone (SPCL) with choline chloride-ascorbic acid with or without dexamethasone. The morphological characterization of the impregnated matrices was evaluated by scanning electron microscopy and by micro-computed tomography (micro-CT). Drug delivery studies were carried out in physiological conditions and the results obtained demonstrate the potential of the developed THEDES to overcome the poor solubility of dexamethasone, while increasing its bioavailability.