Ionic Liquids for Controlled-Release Drug Delivery: Synthesis and Solubility

Controlled-release delivery systems slowly release drug into the body over a long period of time, offering a possible treatment option for patients with chronic conditions who need constant medication. Currently, controlled-release drugs are usually implemented through slowly dissolving or degrading polymeric particles/pills or through osmotic devices, which are limited in which parts of the body they can be effective. While there are drawbacks, controlled-release over long periods of time is especially effective in that compliance and bioavailability is vastly increased over traditional formulations that need to be administered frequently through pills, patches, or eye drops. For example, ocular drug delivery is an excellent area into which controlled release can be applied, as many eye conditions require patients to apply multiple doses of eye drops a day, whereas controlled-release would require drug application on a much less frequent basis. Because of this higher reliability of patient care, controlled-release drug delivery is a highly researched field in pharmaceuticals.

Room temperature ionic liquids (RTILs) are one of the key focuses in this research; RTILs are liquid formulations of two ionic species and are characterized by high viscosity, high relative concentration of drug in formulation, and very low solubility in water. Their low solubility means that RTILs are a prime candidate for delivery of a drug via controlled-release, as they will naturally release small amounts of drug over time without the need for an osmotic or polymeric device. The high viscosity and drug concentration that RTILs exhibit also allow them to remain in a specific area and provide an effective drug concentration over an extended period of time.

The objective of our experiments was to synthesize RTILs using Diclofenac, an anti-inflammatory drug, and to characterize their solubility in aqueous environments over time. Two RTILs were synthesized with two different cationic surfactants (RTIL A and RTIL B) combined with the anionic Diclofenac. The RTILs were synthesized by combining equimolar amounts of Diclofenac and the complementary surfactant in methanol, and the RTIL products were measured to contain a 1:1 ratio of anion to cation. The solubility of the RTILs was evaluated by placing a saturated amount of RTIL in an aqueous solution and measuring concentration of the ionic liquid in solution over time. Concentration measurements were taken using reverse-phase HPLC, and the RTILs were found to reach a saturation concentration of about 1.5mM after around 10 hours. After this solubility curve was determined, the release profile of the drug from the RTIL in aqueous solution was also characterized, and found that both RTILs reached about 8% cumulative release after an 8-day period in the in vitro apparatus used in this study. Based on the solubility and release profiles, RTILs are a prime candidate for further research into their application as controlled-release formulations for ocular drug delivery, and studies should be done on their in vivo pharmacokinetics and pharmacodynamics.