Design of Carnitine-Fatty Acids Ionic Liquids Self Nano Emulsifying Systems To Enhance Oral Drug Delivery

Abstract

The solubility and bioavailability of Biopharmaceutics Classification System (BCS) class IV drugs, characterized by their low solubility and low permeability pose significant challenges for oral drug delivery. Drugs such as venetoclax, olaparib, and vemurafenib exhibit limited therapeutic efficacy due to their poor bioavailability. This thesis explores the potential of amphiphilic carnitine-fatty acid ionic liquids for enhancing drug solubility via self-nanoemulsifying systems (SNES). Thermally stable ionic liquids were synthesized with a relatively unexplored biocompatible quaternary ammonium cation called carnitine and several fatty acids as counter ions. The ionic liquids demonstrated improved solubility of several highly insoluble drugs. The development of SNES was conducted with a series of rigorous screening and optimization experiments, leading to formation of stable nano emulsions. The drug loaded SNES formulations showed reduced globule sizes (<150 nm) and uniform dispersion in various pH buffers, equivalent to the environment of the gastrointestinal tract. A comprehensive pharmacokinetics study compared traditional drug (venetoclax) suspension with drug (venetoclax) loaded SNES with one of the selected emulsion formulations, revealing a notable increase in drug absorption and prolonged drug action. This work underscores the potential of ionic liquids and SNES in revolutionizing drug delivery systems, enhancing drug solubility, stability, and bioavailability, leading to more efficient and effective treatments.