Validation of olive-castor oil (OL-C) blend as a bio-membrane model

Abstract

The need for suitable in vitro biological membrane models for accurate prediction of in vivo biodisposition of potential drug molecules is critical in early-stage drug discovery science. The Olive-Castor oil (OL-C) model was previously reported as possessing a fairly complex architecture compared to routinely used models like octadecylsilane (ODS). However, further studies to validate the bio-relevance of its lipophilicity characterization were recommended. Therefore, to further validate its performance in bio-membrane simulation on a planar chromatographic platform, the retention characteristics of some opioids with similar pharmacophores were determined using a methanol/water binary mixture of varying compositions as the mobile phase on OL-C and ODS platforms. Their limit of agreement for lipophilicity determination was assessed by a Bland–Altman plot, and correlation with in vivo-related biological parameters and calculated molecular descriptors was carried out to evaluate bio-relevance. The lipophilicity indices on ODS were higher than those on OL-C for all the evaluated opioid compounds. The Bland–Altman plot revealed a low level of agreement between the two lipophilicity determinations. OL-C gave higher correlations with all the computed molecular descriptors, pharmacokinetic parameters (AUC: 0.41 vs. 0.23; C_max: 0.22 vs. 0.054), and the in vivo-related bioactivity descriptors (Plasma Protein Binding (PPB): 0.43 vs. 0.29; Human Intestinal Absorption (HIA): 0.62 vs. 0.43; Blood–Brain Barrier (BBB) penetration: 0.33 vs. 0.22). OL-C outperformed the widely used ODS as a potential biomimetic platform for lipophilicity profiling of selected small-molecule drugs. This has the prospect of significantly improving accuracy in medicinal chemistry and drug discovery science. Thus, a wider validation study is warranted.