Ana Rita C. Duarte

THEDES, so called therapeutic deep eutectic solvents are here defined as a mixture of two components, which at a particular molar composition become liquid at room temperature and in which one of them is an active pharmaceutical ingredient (API). In this work, THEDES based on menthol complexed with three different APIs, ibuprofen (ibu), BA (BA) and phenylacetic acid (PA), were prepared. The interactions between the components that constitute the THEDES were studied by NMR, confirming that the eutectic system is formed by H-bonds between menthol and the API. The mobility of the THEDES components was studied by PFGSE NMR spectroscopy. It was determined that the self-diffusion of the species followed the same behavior as observed previously for ionic liquids, in which the components migrate via jumping between voids in the suprastructure created by punctual thermal fluctuations. The solubility and permeability of the systems in an isotonic solution was evaluated and a comparison with the pure APIs was established through diffusion and permeability studies carried out in a Franz cell. The solubility of the APIs when in the THEDES system can be improved up to 12 fold, namely for the system containing ibu. Furthermore, for this system the permeability was calculated to be 14 × 10−5 cm/s representing a 3 fold increase in comparison with the pure API. With the exception of the systems containing PA an increase in the solubility, coupled with an increase in permeability was observed. In this work, we hence demonstrate the efficiency of THEDES as a new formulation for the enhancement of the bioavailability of APIs by changing the physical state of the molecules from a solid dosage to a liquid system.

In situ ATR-IR spectroscopy was used to simultaneously measure the sorption and swelling of carbon dioxide at high pressures in a biocompatible acrylate copolymer poly(methylmethacrylate-co-ethylhexylacrylate-co- ethyleneglycoldimethacrylate), P(MMA-EHA-EGDMA). The $ν$ 3 band of CO 2 dissolved in the polymer (at 2335 cm -1 ) was used to calculate the sorption data and the polymer swelling was determined by analyzing the changes in the absorbance of the $ν$(CO) band (at 1730 cm -1 ) of the polymer. Transmission spectroscopy in the near-IR region was also used to study the sorption of CO 2 in the polymer using combinational and overtone bands. The experiments were carried out in a pressure range of 2.0-12.0 MPa and in a temperature range of 27-40 °C. The data for CO 2 sorption in this polymer obtained by in situ spectroscopic methods have been compared to the data obtained by the gravimetric technique. © 2005 Elsevier B.V. All rights reserved.