Characterization of pharmaceutical solids by scanning probe microscopy.

The force-displacement profiles of four well-characterized materials that represent both soft/hard and plastic/brittle materials have been obtained using a novel nanoindentation technique. Flat surfaces of acetaminophen, potassium chloride, sucrose, and sodium stearate were prepared by melting or recrystallization, and the melting points were measured. Topographic and the corresponding first derivative images were obtained both before and after indentation. The materials were indented using a 10 s loading time, followed by a 2 s hold, and ending with a 10 s unloading time thereby providing a unique force-displacement profile for each material. The loading profile of acetaminophen was discontinuous, whereas the profiles for the other three materials were smooth. The profiles were analyzed and the rank order of hardness was sucrose > acetaminophen > KCl > sodium stearate, which is consistent with the literature. The rank order of the stiffness, which is related to the modulus of elasticity, was sucrose > KCl > acetaminophen > sodium stearate. Given the flexibility and power of this approach, nanoindentation coupled with atomic force microscopy may be a useful means to characterize materials for evaluating tablet-processing conditions, perhaps at a preformulation stage.