A comparison between pure active pharmaceutical ingredients and therapeutic deep eutectic solvents: solubility and permeability studies

摘要

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 themis an active pharmaceutical ingredient (API). In this work, THEDES based on menthol complexed withthree different APIs, ibuprofen (ibu), BA (BA) and phenylacetic acid (PA), were prepared. The interactionsbetween the components that constitute the THEDES were studied by NMR, confirming that the eutecticsystem is formed by H-bonds between menthol and the API. The mobility of the THEDES components wasstudied by PFGSE NMR spectroscopy. It was determined that the self-diffusion of the species followed thesame behavior as observed previously for ionic liquids, in which the components migrate via jumpingbetween voids in the suprastructure created by punctual thermal fluctuations. The solubility and permeabilityof the systems in an isotonic solution was evaluated and a comparison with the pure APIs wasestablished through diffusion and permeability studies carried out in a Franz cell. The solubility of theAPIs when in the THEDES system can be improved up to 12 fold, namely for the system containingibu. Furthermore, for this system the permeability was calculated to be 14 105 cm/s representing a3 fold increase in comparison with the pure API. With the exception of the systems containing PA anincrease in the solubility, coupled with an increase in permeability was observed. In this work, we hencedemonstrate the efficiency of THEDES as a new formulation for the enhancement of the bioavailability ofAPIs by changing the physical state of the molecules from a solid dosage to a liquid system.