(396c) The Development of Anti-Inflammatory Drugs As Ionic Liquids for Topical Drug Delivery

Ionic liquids (ILs) are organic salts whose melting points are below 100°C and are composed entirely by ions.  Due their physicochemical properties, they have been used in wide variety of applications such as green solvents in chemical syntheses and separations.  Most recently, ionic liquids have attracted a great deal of attention due the large number of possible cation-anion combinations of active pharmaceutical ingredients (APIs) that can produce ionic liquids with biological activities.  Several ionic liquids can be in a liquid state at room temperature and some of their benefits include improved solubility, stability, bioavailability and alternative ways for drug delivery. These room temperature ionic liquids (RTILs) are very attractive candidates for topical drug delivery, since there is no need to add any solvent to the active pharmaceutical drug.  In addition, the lipophilicity of the ionic liquid can be tuned by proper selection of the counterion and therefore it will facilitate the absorption of the drug into the skin.  Here, we will report the use of several synthesized room temperature ionic liquids (RTILs) from active pharmaceutical ingredients for topical drug delivery.  The RTILs synthesized incorporate an anti-inflammatory drug with different GRAS (Generally Regarded as Safe) and inactive ingredients used in pharmaceutical formulations.  Anti-inflammatory drugs are used in the treatment of mild to moderate pain and inflammation. The most serious side effects of anti-inflammatory drugs are caused by the systemic absorption of the drug and can include kidney failure, liver failure and ulcers.  Our goal is to eliminate these serious side effects by employing a topical anti-inflammatory drug in the form of an ionic liquid.  The RTILs were synthesized through a salt metathesis reaction and they were characterized by spectroscopic and thermoanalytical techniques (i.e. NMR, DSC).  Drug permeability experiments were also performed to determine their transport ability through the skin. Details about the synthesis, properties and permeability experiments of the RTILs will be discussed.