Browsing by Author "Colombo, Italo"

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    Exploring the shape influence on melting temperature, enthalpy, and solubility of organic grug nanocrystals by a thermodynamic model
    (ACS Publications, 2017-06-14) Chiarappa, Gianluca; Piccolo, Andrea; Colombo, Italo; Hasa, Dritan; Voinovich, Dario; Moneghini, Mariarosa; Grassi, Gabriele; Farra, Rossella; Abrami, Michela; Posocco, Paola; Pricl, Sabrina; Grassi, Mario
    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 to evaluate the increase of drug solubility, an aspect of paramount importance for poorly water-soluble organic drugs since a solubility increase is reflected in a bioavailability enhancement. In particular, the model considers the effect of nanocrystals shape (spherical, cylindrical, and parallelepiped-shaped) and morphology (from platelet to needle nanocrystals) on the melting temperature and enthalpy reduction with crystal size decrease. Nimesulide, a typical nonsteroidal and poorly water-soluble drug with anti-inflammatory action, has been chosen as a model drug to test model reliability. Model outcomes suggest that the reduction of melting temperature and enthalpy mainly depends on the ratio between crystals surface area and volume, i.e., on the ratio between the number of surface and bulk molecules constituting the nanocrystal network. The obtained prediction of solubility enhancement and the successful comparison with the outcomes obtained from a molecular dynamics approach, in terms of melting temperature and enthalpy decrease, have confirmed the reliability of the proposed model.
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    Reduction of melting temperature and enthalpy of drug crystals: Theoretical aspects
    (Elsevier, 2013-04-06) Hasa, Dritan; Voinovich, Dario; Perissutti, Beatrice; Grassi, Gabriele; Fiorentino, Simona; Farra, Rossella; Abrami, Michela; Colombo, Italo; Grassi, Mario
    This review deals with the mathematical models describing the reduction of melting temperature and enthalpy of solids in the nano-size range. In particular, the attention focuses on the thermodynamic based models that are theoretically solid and can be suitably used in the case of organic drugs. Indeed, while much effort has been put in the past to study the melting of metal nano-crystals, little work has been done for organic drug nano-crystals. However, due to the high potential of drug nano-crystals (their solubility increases with size reduction), this theme has become more and more important in the pharmaceutical field. Accordingly, this review, after illustrating the physical frame of drug melting, focuses on the thermodynamic aspects required to describe the melting of spherical and not spherical nano-crystals. Finally, the reliability of some models is tested against the results coming from X-rays analysis in the case of two organic drugs (griseofulvin and nifedipine). This test proved models strength.