Borneol-caprylic acid deep eutectic solvent (DES) based microemulsion gel for improved topical delivery of ivermectin

Ivermectin (IVM), a broad-spectrum and hydrophobic antiparasitic drug, is used topically for the treatment of inflammatory skin conditions such as rosacea. The hydrophobicity of IVM and its limited solubility in lipid vehicles necessitate the development of new topical delivery approaches. Here, we evaluate the potential of deep eutectic solvent (DES) to improve the solubility of IVM, followed by the development of a DES-in-water microemulsion gel to improve the topical delivery of IVM. We demonstrate that borneol, a hydrophobic bicyclic terpene alcohol with penetration-enhancing capabilities, and caprylic acid, a short-chain saturated fatty acid, can form DESs with long-term room temperature stability. Borneol-caprylic acid DESs showed a remarkable ability to solubilize IVM (> 600 mg/g). Further, borneol-CA DES containing solubilized IVM was transformed into a stable microemulsion and subsequently into a microemulsion-based gel (IVM-DES-ME-Gel). IVM-DES-ME-Gel (1% w/w IVM) showed slower in vitro drug release compared to the marketed IVM cream (1% w/w IVM) in the modified dissolution apparatus with immersion cells. Interestingly, IVM-DES-ME-Gel showed significantly higher (∼4-fold) deposition of IVM into the porcine ear skin compared to the marketed IVM cream. Thus, borneol-CA DES-in-water microemulsion gel can be useful in improving the topical delivery of hydrophobic drugs.