Download Crystal pressure in nanoscale pores Many pharmaceutical

Breaking up isn’t hard to do: Crystal pressure in nanoscale pores
Many pharmaceutical compounds are poorly soluble in water. This is problematic because most
pharmaceuticals are delivered orally and must dissolve in the gastrointestinal fluid to be absorbed by
the body. Drug dissolution rate is proportional to surface area, so a common formulation strategy is to
structure drugs as small as possible to maximize surface area. A simple approach to create very small
particles is to structure the compounds within the nanoscale pore space of a colloidal packing. The
resulting composite undergoes rapid disintegration in water and the exposed drug exhibits dramatically
improved dissolution rates. We hypothesize that composite breakup is driven by the growth of
nanoscale crystals, which exert a pressure on the walls of the confining pores. To test this hypothesis,
we systematically vary the amount of water permitted into the composite and use calorimetry to
monitor the evolution of the crystal size distribution as a function of water content. To exert sufficient
pressure to overcome the tensile yield stress of the composite, the crystals must be fed by a
supersaturated phase. Our results suggest that differences in crystal curvature due to crystal
confinement and crystal size polydispersity generate the necessary supersaturation. These results are
relevant not just for drug formulations, but for understanding physical processes such as salt damage to
buildings and road damage due to frost heave.
Breaking up isn’t hard to do: Crystal pressure in nanoscale pores, Masters’ Defense by Emily Berglund,
MS Student, Chemical & Biological Engineering, Montana State University, April 5th, 2017.