Ionic Liquid-In-Oil Microemulsions Prepared with Biocompatible Choline Carboxylic Acids for Improving the Transdermal Delivery of a Sparingly Soluble Drug

• Published in: Pharmaceutics Vol. 12; no. 4; p. 392
• Main Authors: Islam, Md Rafiqul, Chowdhury, Md Raihan, Wakabayashi, Rie, Kamiya, Noriho, Moniruzzaman, Muhammad, Goto, Masahiro
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24-04-2020; MDPI
• Subjects: Biocompatibility; biocompatible; Drug delivery systems; Drugs; ionic liquid; microemulsion; Microemulsions; Permeability; Surfactants; transdermal drug delivery system; Transdermal medication; United States > US; Austria; Japan; ionic liquid; biocompatible; transdermal drug delivery system; microemulsion
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics12040392

The transdermal delivery of sparingly soluble drugs is challenging due to of the need for a drug carrier. In the past few decades, ionic liquid (IL)-in-oil microemulsions (IL/O MEs) have been developed as potential carriers. By focusing on biocompatibility, we report on an IL/O ME that is designed to enhance the solubility and transdermal delivery of the sparingly soluble drug, acyclovir. The prepared MEs were composed of a hydrophilic IL (choline formate, choline lactate, or choline propionate) as the non-aqueous polar phase and a surface-active IL (choline oleate) as the surfactant in combination with sorbitan laurate in a continuous oil phase. The selected ILs were all biologically active ions. Optimized pseudo ternary phase diagrams indicated the MEs formed thermodynamically stable, spherically shaped, and nano-sized (<100 nm) droplets. An in vitro drug permeation study, using pig skin, showed the significantly enhanced permeation of acyclovir using the ME. A Fourier transform infrared spectroscopy study showed a reduction of the skin barrier function with the ME. Finally, a skin irritation study showed a high cell survival rate (>90%) with the ME compared with Dulbecco's phosphate-buffered saline, indicates the biocompatibility of the ME. Therefore, we conclude that IL/O ME may be a promising nano-carrier for the transdermal delivery of sparingly soluble drugs.