The poor performance of PS85 and Span 85 in particular could indicate an activity cli relationship between APR shielding and aliphatic content, reected in the positive coordi-nates in latent space of descriptors concerning hydrocarbon content for both components, in the region of cluster 2. Atom and bond polarisability are both inuential in the formation of cluster 1 (negative value for component 1 and positive value for component 2, but mean polarisability is within cluster 2. This apparent discrepancy can be explained by the more highly mixed content of the well-performing ethoxylated compounds, having high molecular weights and their structures comprising polarisable and nonpolarisable bonds and atoms interspersed; conversely, those with a higher mean polarisability and less polarisable bonds and atoms have more chemically compact head groups, consisting of a small number of atoms with a high polarisability, and smaller hydrophobic tails, leading to a higher ratio of polarisability to molecular weight. This indicates that the shielding of APRs by excipients is better achieved by structures which have larger, but less extreme, polar character, like that which can be achieved by repeating ethoxylate units. Additionally supporting this hypothesis is the position of E-state descriptors that describe double-bonded oxygen (SdO and NdO) and the number of acid and base groups (nAcid and nBase). The mean van der Waals volume can also be found in this region, which could also be explained by the presence of bulky head groups in phospholipids, which are also found in this area, as opposed to the lower occupational volume of PEG chains. Further evidence which supports this hypothesis are the positions and relative importance of the topological radius, topological polar surface area, and the number of rotatable bonds. Qualitatively, many of these qualities can be found in compounds with high PEG content, and the data reect the preferential interaction to APRs of polysorbate species and linear compounds with high PEG content.