Project PTDC/QUI-QUI/098216/2008
Polymorphism in Organic and Organometallic Molecular Solids: Structure and Energetics
PI: M. E. Minas da Piedade
(2010-2012)
The main goals of this project are: (i) the crystallization of different organic polymorphs and solvates, or the preparation of identical crystalline forms with different morphologies; (ii) the investigation of the relationship between structure and energetics, and the outline of the stability domains of the obtained materials; (iii) for materials with terapeutical interest, their evaluation in terms of tabletting and dissolution in model physiological media.
The initial target molecules will be drugs, such statins (e.g. lovastatin, symvastatin, and their salts) or nicotinic acid and its derivatives, but other molecules of industrial importance may also be investigated (e.g. hydroxybenzoyl compounds, commonly used as preservatives in creams or ointments). The strategy involves (i) controlled crystallizations from different solvents (e.g. controlled evaporation and cooling, addition of antisolvent agents); (ii) determination of solubility curves via equilibrium techniques (e.g. the solid residue or spectrophotometric methods), and supersaturation studies (metastable zone width determinations) by using an automatic reactor recently developed in our laboratory; (iii) the structural and energetic characterization of the obtained solids and the outlining of their thermodynamic stability domains, by using methods such as X-ray diffraction, microscopy, differential scanning calorimetry, thermogravimetry, combustion calorimetry, reaction-solution calorimetry, and computational chemistry; (iv) for materials with potential pharmaceutical interest, their evaluation in terms of tabletting, using mechanical tests, and in terms of release from the tablets by dissolution compendial tests described in the European and Portuguese Pharmacopoieas, and required by the Health Authorities (EMEA and Infarmed).
One of the main strengths of the present project is the promotion of the collaboration between three groups from nearby institutions, whose scientific interests, expertise (molecular energetics, molecular and crystal structure determination, thermal analysis, pharmaceutics and and pharmaceutical technology), and equipments are largely complementary. It is, in fact, rare to find in such close proximity a research team with the ample combination and overlap of competences necessary to the investigation proposed in this project. This will allow a systematic and wide scope approach to the research problems, which is hardly ever seen in the literature.