Exploring the Shape Influence on Melting Temperature, Enthalpy, and Solubility of Organic Drug Nanocrystals by a Thermodynamic Model

• DOI: 10.1021/acs.cgd.6b01714
• Publication Date: 2017-06-14T20:45:38Z
• Authors: Gianluca Chiarappa; Andrea Piccolo; Italo Colombo; Dritan Hasa; Dario Voinovich; Mariarosa Moneghini; Gabriele Grassi; Rossella Farra; Michela Abrami; Paola Posocco; Sabrina Pricl; Mario Grassi
• Keywords: Hildebrand solubility parameter

This paper focuses on a thermodynamic model built to predict the reduction of organic drug melting temperature and enthalpy with nanocrystal size decrease. Indeed, this valuable information enables us evaluate increase solubility, an aspect paramount importance for poorly water-soluble drugs since solubility is reflected in bioavailability enhancement. In particular, considers effect nanocrystals shape (spherical, cylindrical, parallelepiped-shaped) morphology (from platelet needle nanocrystals) crystal Nimesulide, typical nonsteroidal anti-inflammatory action, has been chosen as test reliability. Model outcomes suggest that mainly depends ratio between crystals surface area volume, i.e., number bulk molecules constituting network. The obtained prediction enhancement successful comparison from molecular dynamics approach, terms decrease, have confirmed reliability proposed model.