Use of Atomic Force Microscopy (AFM) to monitor surface crystallization in caffeine-oxalic acid (CAFOXA) cocrystal compacts

Abstract

Our objective was to monitor the surface crystallization in disordered caffeine-oxalic acid (CAFOXA) cocrystals following exposure to elevated water vapor pressure. This was accomplished using atomic force microscopy (AFM). Disorder was induced in the cocrystal particles by the common pharmaceutical unit operations of milling and compaction. The ‘activated’ solid, upon exposure to elevated water vapor pressure, had a high propensity to sorb water. This led to a rise in molecular mobility and the surface underwent rapid crystallization to form needle shaped crystals of CAFOXA. Using AFM height and phase imaging, we were able to directly visualize phase transformations on the compact surface. The milled compacts exhibited higher processing induced disorder than the unmilled compacts, thereby accelerating the surface recrystallization.