A detailed, fundamental understanding of the surface properties of molecular crystals and their interaction with adsorbing molecules (e.g. excipients) is important for tailoring the stability of formulations and the bioavailability of Active Pharmaceutical Ingredient (APIs). Few fundamental experimental studies with surface sensitive probes have been carried out for organic molecular crystals. X-ray photoelectron spectroscopy (XPS) is an established surface analysis method in the fields of adsorption, catalysis and surface chemistry of inorganic crystals. It has high surface sensitivity, probing approximately the top 1-3 nm of a crystal, and allows surface elemental analysis combined with the determination of the chemical state of the elements. To explore the possibilities and limitations of XPS for the surface characterisation of molecular crystal systems, investigation has been made on a range of paracetamol systems, three different poloxamers and blends of paracetamol with poloxamer 188. It was found by investigations of a range of polycrystalline paracetamol forms that the C1s, N1s and O1s core level emissions from the amide group of paracetamol allow to quantify, for the first time, the influence of surface contamination and adsorbed species on the paracetamol XPS data. Results of quantitative XPS analyses must be critically evaluated taking the material and energy-specific escape depth of the photoelectron signals into account. Analysis of the polycrystalline powder samples, including two different polymorphs and various partially amorphous forms of paracetamol, indicated that the core-level shifts associated with varying intermolecular interactions do not perturb the local electronic structure variations in paracetamol enough to become detectable through chemical shifts in the core level photoemission spectra. Subsequently, large, high quality single crystals of the monoclinic form I (with facet diameters between ~5 and ~10 mm) were obtained from different solvents (methanol, ethanol, acetone) to examine the influence of the crystallisation medium on the surface properties. Small spot XPS analysis was performed in several areas across facets to examine the possible influence of roughness and other lateral inhomogeneities. Careful curve-fitting of all results reveals only minor variations in the XPS data as a function of facet orientation, crystallisation medium or degree of crystallinity. Moreover, results indicate that any variations seen in XPS data very likely stem from low-level surface contamination, which is very difficult to avoid, even in a clean-room laboratory environment. In fact, the results indicate that the level of surface contamination depends significantly on the crystallisation apparatus cleanliness. Even minute concentrations of surface active components in the solutions, i.e. below the detection level of techniques for routine analytical methods, are likely to cause significant surface concentrations on crystal facets emersed from the solutions. The study thus highlights the paramount importance of microscopic surface cleanliness when assessing macroscopic facet-specific phenomena such as contact angles. Finally, XPS was employed to analyse milled and physical mixtures of paracetamol with poloxamer 188 at different percent. At minimum mass percentages poloxamer 188 adsorbs on the paracetamol surfaces; in the presence of poloxamer 188 excess the conformation of adsorbed poloxamer on the paracetamol surface changes. Studies of radiation damage on the poloxamer samples were performed both for several pure polxamers as well as for milled mixtures with paracetamol. They allowed the proposal of radiation-induced degradation mechanisms.
|Date of Award||31 Dec 2011|
- The University of Manchester
|Supervisor||Sven Schroeder (Supervisor)|
- Paracetamol, X-ray Photoelectron Spectroscopy, excipients, surface analysis