We present a strategy to improve the delivery and bioavailability of phosphoethanolamine (HPEA) nutraceuticals employing an ionic liquid (IL) strategy pairing HPEA as anion source with different counterions, including choline (Ch), arginine (AR), tetrabutylammonium (TBA), n-ethyl-butylamine (EBA), butylamine (BA), hexylamine (HA), octylamine (OA), and pentadecylamine (PDA). Among these, [TBA][PEA], [HBA][PEA], [HEBA][PEA], [HAR][PEA], and [Ch][PEA] fall within the definition of ILs. Additionally, 15 nonstoichiometric ionic compounds were prepared by adding excess HPEA or cation precursor to the 1:1 stoichiometric salt, where some led to the dicationic ILs [Ch]2[PEA] and [TBA]2[PEA], as revealed by spectroscopic results. All the newly prepared compounds exhibited improved aqueous solubility by at least 4–53 times over the commercial HPEA formulations (e.g., calcium salt, [Ca][PEA]2) that have poor solubility mainly due to high crystallinity. We found that the aqueous solubility of poorly-soluble HPEA can be greatly enhanced using IL-forms through pairing with suitable counterions, suggesting new fully water-miscible composition alternatives with potential improved bioavailability and delivery are possible.
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