The Detection and Quantification of Nonyl Phenyl Ethoxylate Surfactant on Paracetamol Single Crystal Surfaces

Much work has been done in the mechanisms of surfactant adsorption to inorganic compounds. Very little work has been on the molecular basis of these interactions, and almost no work has been on the molecular basis of surfactant adsorption to organic molecular crystals. A major reason for this is that non-destructive techniques with sufficient surface sensitivity, on the order of < 5nm, have not yet been made available to researchers. Until recently, the techniques that give information on this level require either destructive techniques, for example, secondary ion mass spectrometry (SIMS), or conductive samples such as X-ray photoelectron spectroscopy (XPS), or are limited in the nature of atomic-scale information that can be obtained, such as atomic force microscopy (AFM). Recent advances in the use of XPS equipment, such as near-ambient pressure XPS (NAP-XPS), have opened up this technique to researchers interested in the study of insulating organic compounds. In terms of complex formulated products (CFPs), the tailoring of formulations by design would benefit from a detailed fundamental understanding of the relationship between molecular-level properties and the performance of API physical forms, including inter-facial interactions with excipients. In this work, the form I paracetamol single crystal and Tergitol NP-9 nonyl phenyl ethoxylate surfactant were used as model compounds. This model was then used to determine whether adsorbed Tergitol NP-9 could be detected and quantified at the paracetamol surface by NAP-XPS. Tergitol NP-9 quantification was indeed found to be possible, in terms of relative contribution to XPS signal and it was possible to calculate layer thicknesses. This was initially made possible by supporting density functional theory calculations and XPS analysis of ultra-pure samples, which was followed by the determination of a practical method for the removal of additional carbonaceous contamination from the paracetamol surface. Finally, outputs were used to calculated not only the layer thickness and relative contributions from Tergitol molecules, but it was also possible to determine the orientation and configuration of adsorbed Tergitol NP-9.