Molecular dynamics simulation of aspirin dissolution

Abstract

Molecular dynamics simulations of the dissolution of aspirin in water are reported. Crystals initially cubic and cylindrical in shape are considered, and the influence of temperature is examined. All simulations are carried out in a manner designed to prevent the build up of any significant concentration of aspirin in solution, physically corresponding to sink conditions. It is found that aspirin dissolution follows a three stage mechanism similar in most respects to earlier observations for nanocrystals of NaCl and urea. In the initial stage, molecules are first lost from corners and edges of the crystal, the crystal is solution annealed into a particular limiting shape, that then persists throughout a large fraction of the dissolution process. For aspirin, initially cubic crystals anneal into a cylindrical shape, in contrast with the near spherical shapes attained by cubic NaCl and urea crystals. In an intermediate stage, during which most of the crystal dissolves, the dissolution rate is well described by a simple classical model which assumes that the rate is proportional to the active surface area of the crystal. For aspirin, the active surface area is identified as the curved surface of a cylinder for both crystal shapes. In the final stage, the small remaining crystal looses its structure and rapidly dissolves. Given that a similar three stage mechanism applies to crystals as varied as NaCl, urea, and aspirin, we conjecture that this mechanism is possibly quite general, and might apply to many ionic and molecular crystals. As for NaCl and urea, an analysis of the activation energy associated with aspirin dissolution strongly suggests that detachment of molecules from the crystal is the rate determining step, at least under the sink conditions.