The amphiphilic nature of many pharmaceutical active ingredients often makes them difficult to solubilise and leads to significant wastage through non-optimal dosage. In this study it is shown that highly concentrated liquid formulations can be produced from pharmaceutical active ingredients which either contain a strong hydrogen bonding functionality e.g.-OH or-COOH or a quaternary ammonium moiety. These mixtures can overcome solubility issues in water as the eutectics prevent recrystallization of the active ingredient when dispersed in water. The depression of freezing point for these eutectic mixtures is modelled using the enthalpy of hydrogen bond formation which was calculated using calorimetric data. The study also demonstrates that complex drug molecules which exhibit polymorphism such as Adiphenine and Ranitidine can be formulated into a homogeneous liquid and the hydrogen bond donor can also be a pharmaceutical active ingredient e.g. aspirin.

Deep eutectic solvents (DESs) have been used for the purification of oils and the extraction of active ingredients from natural products but little is known about the mechanism of the extraction process. In this study a variety of molecular solutes are dissolved in alkanes and the thermodynamics of transfer into six DESs have been quantified. It is shown that the transfer of most solutes into the DES is endothermic and driven by entropy. The largest partition coefficients were demonstrated by the liquids with the lowest surface tensions and this is thought to arise because the enthalpy of hole formation controlling the rate of solute transfer. Accordingly, it was shown that the size of the solute has an effect on the partition coefficient with smaller solutes partitioning preferably into the DES. As expected, solutes capable of strongly hydrogen bonding partitioned much better into the DES as the enthalpy of transfer was negative.

No abstract

Deep eutectic solvent (DES) is a class of ionic liquids, consisting of a mixture generally formed by combining hydrogen bond donors (HBDs) such as alcohols, amides and carboxylic acids with various quaternary ammonium salts. The decrease in melting points of the constituents is due to the charge delocalization during formation of hydrogen bonding between the hydrogen bond acceptor with the hydrogen bond donor. This can be considered one of the main reasons for increasing solubility and absorption of DESs. Most active pharmaceutical ingredients (APIs) have polar functional groups containing amide, carboxylic acid, alcohol or quaternary ammonium groups. These tend to increase the melting point of the compounds, but they can be used to form eutectic mixtures. While this concept has previously used, the combination of quaternary ammonium salts with amides, carboxylic acids and alcohols can result in large depressions of freezing points and so-called deep eutectic solvents are formed. DESs mix readily with water and so could increase the uptake of APIs. In this study, pharmaceutical deep eutectic solvents (PDESs) are formulated from 3 APIs: imipramine HCl, ascorbic acid and catechol. These PDESs were used to plasticise gelatine. It is shown that the materials formed can be used to increase the rate of API uptake via both oral and transdermal delivery modes. Thus, the concentration of the PDESs in solution reaches the maximum before the pure drugs. Particularly for catechol, after 1 s, the dissolution of the PDESs was more than twice that of the pure drug. Moreover, the transdermal delivery mode uptake of the PDES based on imipramine HCl from the patch after 15 min was found to be 65% compared with just imipramine HCl which released only 20%. Graphical abstract

In this work, a novel production of "deep eutectic solvents (DESs)" has been utilised for the elimination of sulfur composition, particularly from crude oil by liquid-liquid extraction. Herein, we present the first demonstration of the use of novel DESs formed by phenol, catechol, resorcinol and o-cresol as "hydrogen bond donors (HBDs)" with trimethyl hydroxyammonium chloride (ChCl) as the hydrogen bond acceptor to affect the efficient separation of organosulfur compounds from diesel. These DES electrolytes have been applied for the sulfur extraction from Iraqi real diesel fuel as determined using X-ray florescence sulfur measurements. The optimisation condition factors in this research have been studied, containing reaction time, the temperature of extraction process, the ratio of mass of diesel to DES and regeneration of DESs. The results indicated that phenol-based DESs extracted more than 38% of S-compounds from true diesel fuel when the mass ratio DES:fuel was 1:2 at 55 °C. Anhydrous ferric chloride (FeCl 3) was also utilised as a catalyst in this work, where it was demonstrated that charge-dipole interaction between the DES and sulfide compounds was the key driving force behind the desulfurization process. We have shown that the extraction efficiency could be summarised as o-cresol + ChCl < catechol + ChCl < resorcinol + ChCl < phenol + ChCl. More than 44% of sulfur species could be removed when a 1:1:1 molar ratio of ChCl: phenol: acetic acid was utilised with H 2 O 2 as an oxidant.