Development and Optimization of Orally and Topically Applied Liquid Crystal Drug Formulations

Abstract: Liquid crystal (LC)-forming lipids represent an important class of biocompatible amphiphiles and their application extends to cosmeceutical, dietary, and pharmaceutical technologies. In the present study, we aimed to develop strategies for designing and optimizing oral and topical LC formulations by evaluating their in vitro and in vivo drug absorption performances. C17-Monoglycerol ester (MGE) was used as a LC-forming lipid. p-Amino benzoic acid, methyl PABA, ethyl PABA, and sodium fluorescein were selected as drug models with different physiochemical properties. Various oral and topical LC formulations were designed based on changes in the LC forming lipid contents in the formulations and entrapped with different physiochemical properties of the drugs. The LC phase structures were evaluated using small-angle X-ray scattering (SAXS). The drug-release profiles from LC formulations were determined using a dialysis membrane method. In vivo oral absorption of LC formulations was conducted in Wistar rats. Furthermore, the skin penetration of drugs from LC formulations was investigated by in vitro skin permeation studies. As a result, although the release profile was influenced by changes in MGE concentration, it was more dramatically influenced by changes in the physiochemical properties of the entrapped drugs. Drug absorption after oral and topical administration of LC formulations was dramatically affected by the concentration of MGE. The concentration of LC-forming lipid and the physiochemical properties of entrapped drugs are key issues for good performance of the LC formulations in various pharmaceutical applications. The present results could enable researchers to manipulate LC formulation approaches intended to improve the oral absorption and skin permeation of drugs.