The in Vitro Lipolysis of Lipid-Based Drug Delivery Systems: A Newly Identified Relationship between Drug Release and Liquid Crystalline Phase

The purpose of this study was to offer a new insight into the microstructure changes during in vitro lipolysis of five lipid-based drug delivery formulations belonging to different lipid formulation types. Five lipid-based formulations of indomethacin were investigated using an in vitro lipolysis model. During lipolysis, microstructures of the intermediate phase formed by lipolytic products were observed. The results showed that the time of liquid crystal formation during in vitro digestion for these formulations was Type I > Type II > Type IIIB > Type IV > Type IIIA (p < 0.0 5). After lipolysis, the drug releases from these formulations were determined. The results showed that the amount of drug distributed in the aqueous phase, obtained by ultracentrifuge after lipolysis, was, astonishingly, in inverse rank order of the above mentioned, that is, Type IIIA > Type IV > Type IIIB > Type II > Type I (p < 0.05). These results showed that the liquid crystalline phase probably has a critical influence on the fate of the drug during in vitro lipolysis and suggested that the liquid crystalline phase facilitated drug precipitation. These findings may improve the understanding of lipolysis of lipid-based drug delivery systems for designing better delivery system.