SCREENING, SYNTHESIS AND CHARACTERIZATION OF BIODEGRADABLE IONIC LIQUIDS FOR ENHANCED SOLUBILITY OF SPARINGLY SOLUBLE DRUGS

In the pharmaceutical industries and in modern medicine, it is well known that
many promising drugs that are sparingly soluble in conventional solvents never enter a
formulation stage due to their poor solubility as well as difficulties in delivery. In an
effort to overcome this limitation, ionic liquids (ILs) as a new class of solvents, were
used to enhance the solubility of two sparingly soluble drugs, Acyclovir (ACV) and
Methotrexate (MTX). Due to theoretical availability of enormous ILs, COSMO-RS as
a physically well-established model was used to screen the solubility of drug molecules
in ILs and investigate possible solvation interactions between drugs and ILs. With
regard to COSMO-RS predictions, five ILs were selected. Diethylammonium acetate,
triethylammonium acetate, tributylmethylphosphonium methylsulfate, choline acetate
were successfully synthesized and characterized and 1-ethyl-3-methylimidazolium
acetate was commercially available. Predicted solubility results were validated
experimentally and a good agreement was observed between experimental and
predicted results. ILs tested in this work, showed higher solubility for ACV and MTX
in comparison to available conventional solvents. Closed bottle test was performed on
selected ILs to comprehend the biodegradability of ILs, which resulted in three readily
biodegradable ILs.