Computational and Experimental Models of Type III Lipid-Based Formulations of Loratadine Containing Complex Nonionic Surfactants

Type III lipid-based formulations
(LBFs) combine poorly water-soluble
drugs with oils, surfactants, and cosolvents to deliver the drugs
into the systemic circulation. However, the solubility of the drug
can be influenced by the colloidal phases formed in the gastrointestinal
tract as the formulation is dispersed and makes contact with bile
and other materials present within the GI tract. Thus, an understanding
of the phase behavior of LBFs in the gut is critical for designing
efficient LBFs. Molecular dynamics (MD) simulation is a powerful tool
for the study of colloidal systems. In this study, we modeled the
internal structures of five type III LBFs of loratadine containing
poly­(ethylene oxide) nonionic surfactants polysorbate 80 and polyoxyl
hydrogenated castor oil (Kolliphor RH40) using long-timescale MD simulations
(0.4–1.7 μs). We also conducted experimental investigations
(dilution of formulations with water) including commercial Claritin
liquid softgel capsules. The simulations show that LBFs form continuous
phase, water-swollen reverse micelles, and bicontinuous and phase-separated
systems at different dilutions, which correlate with the experimental
observations. This study supports the use of MD simulation as a predictive
tool to determine the fate of LBFs composed of medium-chain lipids,
polyethylene oxide surfactants, and polymers.