Emergent Liquid State Asthma Medication: Synthesis and Spectroscopic Characterization

Abstract

Many asthma medications are delivered as solid state ingestible, compact tablets. Several problems arise from a drug’s solid state such as low bioavailability and existence of multiple crystalline forms (polymorphism) depleting its effectiveness. The low bioavailability is related to the low aqueous solubility while polymorphic changes can convert a drug into a less or nonactive form. The effectiveness of these drugs can be enhanced by conversion into a liquid state ionic compound. Two approaches can be used: an ionic liquids (ILs) or a double salt ionic liquids (DSILs) approach. ILs and DSILs are ionic salts with MP < 100 oC; an IL is composed of a cation and an anion in a 1:1 molar ratio while a DSIL is obtained by pairing an ion with counterions in varying molar ratios (e.g., one cation with two, three, etc. anions or vice-versa). When applied to pharmaceuticals, both approaches should increase their bioavailability (higher aqueous solubility; like dissolves like), remove the existence of polymorphic forms and add multifunctionality to the final drug (i.e., the pharmaceutical activity of the parent ions is retained).
Our research focuses on synthesizing new DSILs by pairing the cationic form of albuterol asthma drug with docusate anion (a known IL former) and NSAIDs in their anionic form such as ibuprofen and naproxen anion. Albuterol hydrochloride supplies the cation source, whereas sodium docusate, sodium ibuprofen, and sodium naproxen all serve as anion sources. Our presentation will encapsulate the synthesis and spectroscopic characterization of such DSILs.