No abstract

No abstract

No abstract

A deep eutectic solvent (DES) is a eutectic system consisting of hydrogen bond donor and acceptor has been suggested as a promising formulation strategy for poorly soluble drugs. A DES consisting of choline chloride and levulinic acid in a 1:2  molar ratio was used to formulate a liquid solution of the model drug aprepitant. This formulation was tested in vitro (drug release and permeability) and in vivo (rat model) and compared with the performance of amorphous aprepitant and the commercial aprepitant nanocrystalline formulation. In this study a DES formulation is compared for the first time directly to other established enabling formulations. The in vitro drug release study demonstrated that the DES formulation and the amorphous form both were able to induce an apparent supersaturation followed by subsequent drug precipitation. To mitigate the risk of precipitation, HPMC was predissolved in the dissolution medium, which successfully reduced the degree of precipitation. In line with the results from the release study, an in vitro permeation study showed superior permeation of the drug from the DES formulation and from the amorphous form compared to the nanocrystalline formulation. However, the promising in vitro findings could not be directly translated into an increased in vivo performance in rats compared to the nanocrystalline formulation. Whilst the DES formulation (34 ± 4%) showed a higher oral bioavailability compared to amorphous aprepitant (20 ± 4%), it was on par with the oral bioavailability obtained from the nanocrystalline formulation (36 ± 2%).

Deep eutectic solvents (DESs) are formed by a hydrogen bond donor and an acceptor. The hydrogen bond interactions between these two components significantly depress the melting temperature of the mixture. DESs have been used as an alternative for organic solvents in various branches of the chemical industry. Many DESs are very hygroscopic and water is known to change the properties of DESs, but there has neven been a systematic study performed on the deliquesence behavior of DESs. Therefore, this study investigated the thermal and deliquescent behavior of four DESs. The DES mixtures were stored in desiccators at different relative humidities (RH) to investigate the critical RH (RH0) for deliquescence. It was found that, due to the formation of a eutonic mixture, the RH0 to induce deliquescence for a given DES mixture was lower compared to the individual components comprising the DES. The results showed that, even though all investigated DESs had eutectic melting temperatures above room temperature, but due to the low RH0, they were able to appear liquid at room temperature under ambient conditions. The eutonic and eutectic compositions were identified at different compositions for the DESs. The results emphasize that great care must be taken to control the process and storage conditions for DESs.

No abstract

No abstract