title: The development of heated tip force-distance measurements as a novel approach to site-specific characterization of pharmaceutical materials.
abstract: The study describes the development of a novel approach to surface analysis whereby thermal probes are used to perform scanning probe microscopy pull-off force measurements as a function of tip rather than sample temperature. The initial impetus for the investigation was the study of a poorly understood phenomenon associated with microthermal analysis (MTA) whereby the thermal probe is pulled into the surface of a sample following temperature-induced softening. Localized thermomechanical analysis experiments were performed on a range of pharmaceutical materials using TA Instruments 2990 Microthermal Analyzer equipped with a TM Microscopes Explorer atomic force microscope. The system was then interfaced with a second instrument to allow simultaneous probe temperature control and pull-off force measurement. It was found that the pull-in effect is due to the adhesion of the probe to the material at elevated (softening) temperatures. However, it was also noted that for paracetamol tablets the pull-off force increased at temperatures well below the softening associated with melting. This behavior was ascribed to surface polymorphic changes caused by the compression process. The temperature-controlled pull-off force method therefore represents a novel and potentially widely applicable means of detecting surface changes that are not easily observed using isothermal pull-off force measurements or indeed standard MTA studies.
authors.affiliation: School of Chemical Sciences and Pharmacy, University of East Anglia, Norwich, UK.
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Harding
authors.forename: Mike
authors.initials: M
authors.lastname: Reading
authors.forename: Duncan Q M
authors.initials: DQ
authors.lastname: Craig
mesh_terms: D000082:Acetaminophen / Q000032:analysis; D000269:Adhesives; D002138:Calibration; D006358:Hot Temperature; D007052:Ibuprofen / Q000032:analysis; D007213:Indomethacin / Q000032:analysis; D018625:Microscopy, Atomic Force; D004364:Pharmaceutical Preparations / Q000032:analysis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013499:Surface Properties; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D013816:Thermodynamics
chemical_list: D000269:Adhesives; D004364:Pharmaceutical Preparations; D013607:Tablets; D000082:Acetaminophen; D007052:Ibuprofen; D007213:Indomethacin