Solubility of a New Cardioactive Prototype Drug in Ionic Liquids

Abstract

Solubility in different solvents is an intrinsic material characteristic for a defined molecule. The solubility of a new cardioactive prototype drug, 3,4-methylenedioxybenzoyl-2-thienylhydrazone (LASSBio-294), was determined in seven different imidazolium based ionic liquids (ILs). The ionic liquids selected were 1-ethyl-3-methylimidazolium methyl phosphonate; 1-ethyl-3-methylimidazolium ethyl phosphonate; 1-ethyl-3-methylimidazolium acetate; 1,3-dimethylimidazolium methyl phosphonate; 1-butyl-3-methylimidazolium acetate; 1-butyl-3-methylimidazolium tetrafluoroborate; and 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide. In addition, solubility data of LASSBio-294 in water and in mixtures of water and ILs were also measured. For all solvents, the concentration of drug in saturated solutions was determined by high performance liquid chromatography (HPLC). Solid−liquid equilibrium measurements were performed in a range of temperatures from 288.15 K to 308.15 K, at atmospheric pressure. From the solubility data it can be concluded that the drug showed sufficient solubility in five of the tested ILs so that these compounds can be suitable for further crystallization studies. The aim of this work is also to discuss and understand the solubility of LASSBio-294 in these alternative solvents. The results indicate that the solubility of the drug is dependent on IL structural variations (cation−anion combinations).

The A Priori Design and Selection of Ionic Liquids as Solvents for Active Pharmaceutical Ingredients

“…Hence the best choice of solvent in terms of API solubility would be ag ood hydrogen bond accepting anion such as [OAc] À .S imilar trends were predicted and shown by Azevedo et al for as ingle API that would be classified as HBD in this scheme. [15] APIs that have been classified as HBD include albuterol, amoxicillin, aspirin, ibuprofen, naproxen and triclabendazole.…”

“…Based on the studies discussed above, ILs with good hydrogen bond accepting anions are quite often good solvents for the APIs tested, providing a high capacity to dissolve the crude API prior to recrystallization . However, as we will demonstrate in our study, this reasoning cannot be applied to all APIs, and the IL comprising the best hydrogen bond accepting anion does not always result in the highest API solubility.…”

“…The use of ILs for the purification of APIs has not been widely investigated, with only ah andfulo fl iterature reports. [14][15][16][17][18][19] Smith et al investigated the solubility of ibuprofen and acetaminophen in two very similar ILs, with the only difference asubtle variation of the alkyl chain length of the imidazolium cation used. Both ILs featured the same hydrophobic and weakly interacting anion [PF 6 ] À .T he scope of the study was to investigate the potentialt ou se ILs in future crystallization processes of the two pharmaceuticals, by investigating the solubility, [14] whereas the group in al ater paper demonstrated the crystallization of acetaminophen from the IL.…”

Ultrasound assisted crystallization of a new cardioactive prototype using ionic liquid as solvent

“…Our group has previously reported promising results of solubility of LASSBio-294 in seven imidazolium based ionic liquids miscible or partially miscible with water (1- [18]. Interactions such as hydrogen bonds, van der Waals forces and π-π-solvent-solvent interactions permitted to explain the difference of solubility observed.…”

Borax Crystallization Kinetics in a Pitched‐Blade Turbine/Straight‐Blade Turbine Dual‐Impeller Crystallizer

“…It has already been proven that mixing influences crystallization kinetics in single‐impeller systems . But researches concerning dual‐impeller systems are still quite rare , , even though the use of multiple impeller systems is very common in chemical and other related industries.…”