Improving oral absorption of tretinoin by ionic liquids technology

Oral delivery of the hydrophobic tretinoin (Tre) is a significant challenge due to poor solubility and bioavailability. Herein, we describe the potential of ionic liquids (ILs, e.g., [Ch][Ger]), in particular active pharmaceutical ingredient-based ILs (API-ILs, e.g., [Ch][Tre]) and their mixtures (e.g., [Ch][Tre]-[Ch][Ger]), for oral delivery of Tre. [Ch][Tre] provided excellent apparent content of Tre (42.10 g/mL), a 175 million-fold improvement over its water solubility. The cumulative Tre release at 5 min of Tre-[Ch][Ger] and [Ch][Tre]-[Ch][Ger] reached 95% and 97%, respectively. Upon the same oral dosing of Tre in rats, [Ch][Tre]-[Ch][Ger] increased peak blood concentration of Tre by 2.9-fold and total Tre exposure by 3.6-fold. Furthermore, the oral bioavailability of Tre in [Ch][Tre]-[Ch][Ger] was significantly enhanced to 361.4%. It's speculated that the mixture of ILs gave rise to sophisticated solvent structures, making the system more stable to enhance the drug adsorption. In conclusion, our findings highlight the potential of ILs technology as a promising platform for oral delivery of hydrophobic drugs.