Crystallisation of the orthorhombic form of acetaminophen: Combined effect of surface topography and chemistry

A new method for the crystallisation of the metastable orthorhombic polymorph of acetaminophen using colloidal templates with specific surface topographies and surface chemistry is reported in this study. The templates were prepared from silica nanoparticles (220 nm) and their surface chemistry was modified by in situ silanisation using different organo-silanes to attach amino, phenyl, dodecyl and trifluoropropyl functional end groups. Cooling crystallisation was performed on the surfaces of novel colloidal templates using a simple single step rapid cooling method, which resulted in selective crystallisation of the metastable orthorhombic form on the surfaces with a specific surface topography and surface functional end groups in conditions, which typically yielded monoclinic crystal forms. Here, we report crystallisation of the orthorhombic form of acetaminophen at super-saturation c/csat = 1.5, which is lower as compared to the c/csat = 2.0 reported in the literature. The method reported here has shown potential for surface selective polymorphic control of organic molecules using combined effect of surface topography and surface chemistry.