Enhanced solubility of nanostructured paracetamol

Athermodynamic top-down approach was used for quantitative prediction of the influence of size and shape of monoclinic paracetamol nanoparticles on their solubility in pure water. A thorough analysis of published experimental data on the bulk paracetamol solubility in water and its melting properties was performed and a temperature dependence of the limiting activity coefficient of paracetamol in the saturated aqueous solution was assessed. Next, the equilibrium condition for the nanostructured paracetamol solubility is derived considering various nanoparticles shapes and the size-dependent interfacial energy at the solid paracetamol/liquid solution interface. Calculation of solubility was performed for spherical particles of radius 1-50 nmas well as for elongated cylindrical particles of various aspect ratios. Size-dependence of interfacial energy gives a maximal solubility for spherical nanoparticles of some critical radius rc. Predicted solubility of cylindrical nanoparticles is greater than for spherical nanoparticles of the same volume due to higher surface-to-volume ratio and higher average interfacial energy corresponding to shape-dependent changes of particle morphology.