Crystallization Behavior of Acetaminophen in Nanopores

The influence of nanoconfinement on the crystallization behavior of acetaminophen, a polymorphic drug occurring in three different crystalline forms, is investigated. Differential scanning calorimetry (DSC) and wide angle X-ray scattering (WAXS) data for a series of controlled porous glasses (CPGs) filled with acetaminophen are presented. The results show clearly that (i) the usually inaccessible crystalline form III of acetaminophen can be produced in pores with diameters between 22 and 103 nm and that (ii) the life time of amorphous acetaminophen is significantly increased in 10 nm pores. Bulk melting temperature and heat of melting of form III are estimated based on the Gibbs-Thomson equation. The experimental findings are confronted with the predictions of theoretical approaches aimed to describe thermodynamics and crystallization kinetics in nano-sized systems in order to understand the physical background of the observed changes.